Coach to Cure MD. A game-changing strategy.

As a young, high school girl, I walked around the perimeter of the football field, my eyes in the stands looking for friends. I could feel the energy, the excitement, but soon recognized I had to learn about the game, the sport, the rigor, the diligence, the strategy. And, over the years, I did just that. As a college student, I attended Mt. St. Joseph College, at the time, an all girls college. We had no football team, but we were all committed Buckeye fans and spent a considerable amount of time finding reasons to travel to Columbus, not the least of which was to watch the Buckeyes play. In 1968, the Ohio State Buckeyes football team was considered one of the strongest in OSU history. The Buckeyes capped an undefeated season with a dominating 50–14 victory over arch-rival Michigan.

College is a special time in life, with so many wonderful moments, times that, even still today make me smile. That day in 1968, when the Buckeyes won and we knew we would be in Pasadena for the Rose Bowl, I remember the parade as if it was yesterday. The crowd was energized, jubilant. They removed the goal post and headed down High Street toward downtown. The fans were hoisting college students on top of the goalpost, singing and screaming. I was one of those young college students, triumphant and over the moon about that game and the upcoming Rose Bowl. Just thinking about football season reminds me of college, of happy days and now – of opportunities for our sons.

Fast forward to 2010. Jim Tressel, OSU’s coach and one of our biggest supporters will be wearing an armband and leading the Buckeyes to victory! Now, not only am I supporting OSU, OSU is supporting us.

The first time I met Tom in the ICU, I asked about his watch – Notre Dame Champions. Tom played Defense for Notre Dame, recruited by Ara Parsegian. Tom’s father had made a scrapbook of his career – Ignatius High School in Cleveland, followed by the fighting Irish of Notre Dame. Chris and Patrick loved that scrapbook, turning each page, reciting plays, scores, and dreaming dreams. Dreams of the Golden Dome. Dreams of running out on that field. Dreams of scoring. I had my own dreams and over and over, just wished for Chris and Patrick to stand on that field. Just once.

Football is the stuff of dreams for all of us – wishing in our own life to make that Touchdown.

On 9.25.2010, I’ll be watching OSU. Tom will be cheering the Irish. And while we cheer for different teams, we agree on one thing – to End Duchenne. Hundreds of coaches will be wearing the Coach To Cure MD armbands with millions of spectators and all of you, raising awareness, raising money, BUYING TIME…

9.25.2010 is a game changer for Duchenne, a time for all of us to do something, to stand up, to connect to everyone we know and anyone they know. My ‘game plan’ is to connect, to ask family, friends, strangers to help, to TEXT the word CURE to 90999, to give what they can, to get in the game and to be a game changer… for Duchenne.

What will you be doing on 9.25.2010?

Visit Team PPMD's page or create your own page and ask friends and family to support Coach To Cure MD.

Click here

Why did Blake die? Why do some boys die so young?

I first met Whalen, Blake’s dad, just after Blake was diagnosed. It was summer, just before our Annual Connect Conference scheduled in Pittsburgh, PA. Whalen rode his bike from Florida to Pittsburgh. Red-faced, he arrived- tired, hot, and smiling. From that day on, Whalen and Allison were committed to help Blake and every other boy. We met often – conference, marathons, and in Washington.

We lost Blake last week. While showering he fell, fractured his femur and died. We are all asking questions – why are we losing boys so young? what is happening, what is the sequence of events – is the heart giving out, did the fracture initiate a cascade of events? what do we need to learn about these young hearts? what should we do, what could we learn, how could we be more proactive and would that help? How would we know?

When we learn that we lost one of our own and so young, there are no words. It hits in a place some of us never realized existed. Our hearts are broken, we are outraged, but more than that, we want answers. And the truth of the matter is that we actually do not know the sequence of events, nor do we have any answers.

There are many reasons that could cause our sons to die early. They range includes infections, pulmonary events (choking, embolism, respiratory arrest), cardiac events (arrhythmia, infarction)...and the only way we could ever learn about exactly what happened is by autopsy. And that word is so difficult, much too big to fit into our heart and mind.

And when our sons “look so good,” it is impossible to know. And because they are living with Duchenne, they may not know what our definition of ‘feel good’ means. How many times have people said this about your son. And how many times have you choked up, knowing Duchenne hearts are not so strong, Duchenne bones are not so strong, Duchenne muscles are not strong. Our sons faces are photographed on the cameras of our soul; those beautiful faces and eyes that radiate a wisdom many adults would be unable to comprehend and along with that external beauty, we see a fragility, unseen by most, but visible to those that love them.

In fact, the ‘he looks good’ should remind us that external beauty does not provide a full picture. It is the inside that counts, that makes the differences, sometimes between life and death. And we have a lot to learn about heart, about bone, about muscle… and we will.

I have a dear friend who always responds to the ‘how are you’ question in this way…I’m fine and thankful, because in the next 5 minutes everything could change. Life is not a dress rehearsal, appreciate the time you have and use every moment.

God Bless Blake and every other young man that has touched our lives for only a short time. Our fallen heroes. God Bless all of us who will miss them every day of our lives.

(Click here to read Blake's obituary)

Definition of terms

The roller coaster of Duchenne has been in high gear this week with BioMarin’s announcement to halt trials and one day later, Acceleron’s press release about receiving Fast Track Status. I don’t know about you, but in a certain way, it sounds like Fast Track Status should be a high speed train, capable of 220 mph. The reality is that the Fast Track Status train is the same train, with better fuel (expedited review) and more tech support (FDA interaction).

I am pretty sure, everyone may have a different definition of Fast Track Status and thought maybe it would help to clarify what this means in reality.

In 1983, Congress passed the Orphan Drug Act.

Orphan Status:

• Drug (or biologic) for an orphan indication.
• Definition of rare disease– affects less than 200,000 people in the US
• High unmet medical need
• 7 years of market exclusivity
• Tax credit of up to 50% for qualified expenses for research support to support approval of the Orphan drug
• Exemption from several kinds of user fees
• Guidance from FDA staff to sponsors

The Division of Orphan Products is responsible for:

1. granting Orphan Status
2. is able to provide small grants for sponsors (based on application/review)

FDA

Fast Track Status – the purpose of Fast Track Status (accelerated approval and priority review) is to speed reviews and provide more extensive guidance to sponsors about the nature of the evidence that will be required in order to support approval.

• Includes a ‘rolling review’ by FDA, where companies submit modules of an NDA (new drug application) for a rolling review which allows more frequent consultation and dialogue with FDA on issues related to the application.
• Fast Track may include ‘accelerated approval’ which allows the use of surrogate (secondary) endpoints likely to predict clinical benefit. The FDA would likely require post-approval studies in order to collect additional evidence about safety and benefit.
• Fast Track applications may also qualify for ‘priority review’ which means FDA sets a goal of completing reviews within 6 months compared to the standard process of 10 months.

There is one more mechanism you might hear about to facilitate review – Special Protocol Assessment – which allows the FDA to provide expedited assessment of the adequacy or appropriateness of specific clinical trial protocols and to reach an agreement with sponsors about the design and size of a certain trial to support efficacy (benefit) claims. Normally, this is ONLY available at the end of a Phase II trial.

Bottom line: Acceleron has not gotten approval to start the trials in the US yet…Fast Track Status does not mean IND Approval.

This is all very difficult to take in and most of the time, seems pretty confusing. Often patients/families see the designation of Fast Track as some sort of vehicle that may deliver the drug quicker. In essence, because of the expedited review, guidance from FDA is intended for that purpose. But for those of us watching and waiting, heart in hand, it does not answer the ‘when’ question. It is strictly related to the FDA process.

It's the little things.

Genetic Alliance Gene Screen

Last weekend I participated in the Genetic Alliance Gene Screening films (Marfan, Power of Two, Rick Guidotti, Darius Goes West) on Thursday evening. Many of us are already familiar with Darius Goes West (DGW) so I thought I would concentrate a bit on the other films and the common threads that link all of us together. I wondered how the evening would go, sitting through 3 ½ hours of films on specific rare disease.

The films were shown at the E-Street Theater in Washington, DC. Sitting in the darkened room, popcorn in hand, the first film started. It was a film about Marfan’s disease. Like all rare disease, Marfan has a spectrum of disease and patients have typical physical characteristics. The film interviewed several families and their connections to each other. The story was amazing, not only describing the disease process, but clearly demonstrating the beauty of connecting, of working together. Individuals with Marfan have very long arms and legs and sometimes, these patients ‘wear’ their disease, often feeling isolated, alone. The film was perhaps one of the most creative I have seen, utilizing the skills of a professional dancer to teach young people with Marfan to dance, using their long limbs as expressions of individuality. You cannot help but be moved by this film and hopefully you will have an opportunity to see it on PBS.

Rick Guidotti is a professional photographer with a long career capturing the beauty, first of professional models for magazines such as Vogue. At a certain moment, Rick was captured by another beauty, a young woman with Albinism and abruptly changed his focus to portray the beauty of rare disease.

Power of Two, is a story of two young CF patients living in the United States and given new life through organ transplant. These two lovely woman are from Japan, where organ transplantation is not done for a host of reasons. They are promoting organ donation and transplantation in a country where patients are typically not given second chances.

And finally, Darius Goes West, a film about Duchenne and access and the gift of friendship. Darius was Skyped in from Atlanta – a new Darius in a way, healthier after losing considerable weight and smiling, aggressively working on his career in rap music.

Friday, I participated in a leadership seminar at the Genetic Alliance conference and ended the day as a ‘talking head’ in the debate – “Who wears the pants? Evolving power dynamics in clinical care.” The debate concentrated on CARE – basically a discussion of who is in charge. The panel consisted of:

Kemp Battle, Genetic Alliance Council
Barb Biesecker, NHGRI, NIH
Howard Levy, Johns Hopkins University
Marcia Wright, Sickle Cell Disease Association of America, Eastern North Carolina Chapter
Pat Furlong, Parent Project Muscular Dystrophy

The discussion was lively, including obstacles to care (reimbursement, liability, demands on schedule, etc.) and the need for coordinated multi-discipline teams. From my point of view, patients/family members “wear the pants,”, seeking out expertise and experience and advocate for optimal care. At the end of the day, we agreed that in the near future, well trained nurses (nurse practitioners) should take over the world to coordinate patient care …ok, so I admit this may reflect some degree of bias.

Naples

This meeting occurs every 4 years. It is pretty amazing to witness the energy and the enthusiasm in the community. This is one of a long list of meetings focused on neuromuscular diseases and because it was just on the heels of the PPMD Connect Conference in Denver, I’ll just hit the highlights and add in some thoughts along the way.

Eight years ago the meeting was in Canada, just after the 1992 PPMD Connect Conference held in Pittsburgh that year. Many of the presenters from PPMD headed directly to Canada. That year, both Steve Wilton and Judith VanDeutekom were armed with posters describing their work on exon skipping, programs funded by PPMD. Sitting in the Naples meeting, I found myself remembering those early days, when exon skipping was so far away. And now, in Naples, we were hearing results of the early studies – safety, dose escalation, and plans to move forward. Dr. Griggs discussed the upcoming steroid trials and that they have now applied for orphan status for Deflazacort. Annemieke is brilliant. I am always amazed at her ability to present data in a clear, concise, and balanced manner. Two of her colleagues from Leiden accompanied her with posters and presentations and I have to say, they too are brilliant (but I keep thinking they look like they are in high school).


• Presentations and discussion around the results, to date, of exon skipping trial, in the PMO, skipping exon 51 – 7/19 patients showed an improvement in dystrophin levels and only 3/19 patients responded strongly, with the conclusion that we may need higher doses than 20mg/kg.
• Dr. Griggs discussed the upcoming steroid trials and said they had applied for orphan drug status for Deflazacort. Finally! It is long overdue.
• Dr. Muntoni’s presentation included a discussion about the cost of therapies for rare diseases. A child diagnosed with Pompe and treated over a lifetime with Myozyme would cost an estimated $35 million dollars. Is there any wonder why advocacy is important?
• Dr. Bushby presented on Ataluren. Subanalysis suggests a trend toward benefit with low dose. Questions related to biopsy data were answered by Langdon Miller. Dr. Miller talked about the complexity of the biopsies, the number of surgeons performing the procedure, the orientation of the specimen, processing/shipping and collections to a central lab. Many of the specimens have freezing artifact. But they have not given up and will continue to work hard on the analysis in spite of the complexity.
• (poster sessions) Discussed the Dutch study on physical training in Duchenne and “no use is disuse,” as well as quality of life issues.
• Discussions around proactive cardiac care, insulin resistance and dissemination, and implementations of standards of care in Duchenne (Care Considerations).
Because there are so many meetings, and this one, just following PPMD’s Connect Conference, there was little ‘new’ news. I find that the side conversations are the most useful and I typically craft some strategic questions to ask and bring back to PPMD’s staff and scientific advisors. Questions such as:
• What do you see as gaps in clinical care?
• What do you see as barriers to therapies?
• What progress have you made in terms of measuring and validating patient-reported outcomes and do you plan to implement any of these measures as secondary outcome measures for upcoming clinical trials?
• Would it be possible to consider adding non-ambulatory patients (safety) once a registration trial was fully recruited?
• If there was one thing that you could do/change/support to move therapies forward, what would it be?
• Do you worry that there is a therapeutic misconception about what current therapies are likely to deliver?
• Do you have concern about access to emerging therapies?

And I ask for proposals, delivering them to PPMD’s leadership as we plan our strategy to End Duchenne.

A Bedtime Story

Who gets the award for finding the treatment or cure? I received this question over and over and yesterday again, in an email from a parent. She provided a list of each organization and what projects or companies they have supported. In my head, I wanted to say all of us, some of us, what does it matter as long as the drug is developed, the project funded. Her real question was –if I raise money for you, will you get ‘the cure’ for my son? My first thought was to say – ‘cures’ do not come from one group or organization, it does not work that way. Best guess for the cost of developing a new drug is right around the $800 million dollar range and I doubt that anyone would have that ability and/or want to invest every last dollar in a single program. You already know the numbers, 1 out of 8 compounds ever makes it to approval, so it makes sense that any number of investors come in at different times, sharing risk. I went to bed thinking about it, thinking how, for many of us who support research, the projects we fund feel like they belong to us somehow. The projects and the individual who run them become our children in a strange sort of way.

Let’s imagine you are considering having a child. You think of the options: the impact on your life, the impact on your budget, your job, and who you will need to call upon to help you with the baby.
(*novel project – intense review)

You are pregnant, thrilled of course, and take good care of yourself, trying your best to ensure a healthy baby.
(*early data)

The baby arrives, happy and healthy. Let’s call him Gregory. You find yourself overwhelmed. How in the world could someone so tiny take up so much time, cause so much fatigue. You are dead on your feet and need a break and while you love this little one, there are moments when you feel you are not going to make it. And then, there is that first fever, congestion, irritability. You panic. You are up all night watching him breathe. By morning, the baby is improved (why do they always get sick at midnight?) Aunt Betty/Gram or a dear friend walks in the door, hands you a gift certificate for a massage, followed by dinner, and you nearly run for your car.
(*bridge support)

Time flies. Children grow quickly, too quickly, and soon they are running around, under your feet and before you know it, they start school . Gregory enters kindergarten and after a short time, the teacher suggests Gregory is not interested in school, not interested in learning his letters or his numbers and well, by the sound of her voice, it feels like Gregory is not going to be successful. And he’s only 5! This type of attitude is a game changer and you are prepared for battle. This is Gregory, the crazy little man, talkative, smart and not at all what the teacher implies. You search for tools to help and find a wonderful tutor, who makes learning a game about pirates and dragons. Gregory not only learns to read, but begins to drive his family crazy sounding out every road sign and menu option at Burger King.
(*fellowship – additional staff to focus on the project)

Gregory’s parents relax as he seems to adjust well to the schedule and his teachers. Things come easily for Gregory, until 6th grade math. The thing is Gregory can do the work, but he seems preoccupied with sports, video games, and friends. Grades drop. Test scores drop and you know the rest of the story. Parents are upset and the teacher is not budging. Gregory’s parents try everything they can think of from incentives to discipline to pleading. Summer arrives and Gregory barely passes math.
(*some experiments fail, at least temporarily)

The summer was wonderful for Gregory. Nothing about school, but all about friends, swimming, soccer, and video games. His friend’s dad recommends a free on-line video game - Moonbase Alpha. Playing Moonbase Alpha is not simple. Gregory and his friends step into the role of exploration team members and are immersed in a futuristic 3-D lunar settlement. Their mission is to restore critical systems and oxygen flow after a nearby meteor strike cripples a solar array and life support equipment. Gregory is hooked: inspired and engaged in space exploration, learning about science, technology, engineering, and mathetics (STEM education).
(*Interim support? Tox package?)

Gregory is back! He now sees himself working for NASA and one day, joining the team to land on Mars. High school is uneventful. As graduation gets closer, Gregory starts to worry. His cumulative average is 3.5 and his first SAT score is verbal 560 and math 610, good - but not great in terms of his life goal and unfortunately, not quite good enough to get into MIT, and most certainly not the type of credentials he would need for a scholarship. Gregory is devastated. His dream of admission to the best college program that feeds into NASA’s space program seems pretty impossible. With tears in his eyes, Gregory talks to his Uncle Henry about his dreams, his goals, his apparent failure. Henry believes in Gregory, offers to do whatever it takes to help him improve his SAT and generously offers to pay his college tuition. Day and night Gregory prepares for the test. Gregory’s SAT scores improve: 620 verbal and 680 math. He is admitted to Rice College in Texas, a major feeder school for the NASA program.
(*Venture capital)

On a sunny day in June, 4 years later, Gregory walks down the aisle, lifts his arms to receive his Diploma from Rice and while Gregory felt quite prepared to walk on the moon, he realized he would need additional education and resources to step into an aerospace engineering position. Gregory agrees to an internship at NASA, spends time with a range of experts and finds mentors to guide his journey.
(*Partnering)

All this to say, drug development is not accomplished by one person, one organization, or one company. It is accomplished through hard work, vision, opportunity, investment, and ONE VOICE – all focused on a single goal. Every organization/foundation/parent/patient is reaching for the same goal. We all make investments for different reasons, at different times, with different goals in mind; sometimes to fill gaps, often to provide seed money, frequently at just the right time to keep things moving.

And lest we not forget about the seemingly non-sexy stuff such as promoting early diagnosis, accurate genetic testing, registries, standards of care, workshops to identify gaps in care, clinical trials (ambulatory and non-ambulatory) outcome measures, advocacy (NIH, DoD, FDA, HRSA), post market surveillance, and access to therapies… for all boys, everywhere.

No one can do everything, but everyone can do something.
ONE VOICE

Conference 2010

I’m not going to recap the 30+ hours of presentations from this year’s Conference.  We will soon post many of the presentations and Sharon will blog about various presentations and projects over the next weeks and months.  I wanted to tell you a bit about what took place this year and look forward, to share some thoughts about next year… Already you ask?   We spend a lot of time thinking about the Conference, trying to improve it each year, trying to make sure we provide comprehensive information to all stakeholders and working on all fronts in order to accelerate treatments that will stop the progression of the disease for all boys everywhere, that will end Duchenne.  We have not yet decided on the specifics as in date/location, but we have had some conversations about the nuts and bolts.

Pat Moeschen’s keynote was amazing.   Everyone attending the meeting jammed into the room and for the first time ever, no cell phone rang, no one was texting.   We were all listening to Pat.  I would like to say, Pat is the voice of reason, but he is more than that.  Pat is the voice of joy, of laughter, of living a life.   Both the expert and sibling panel were amazing as well, with full audience participation.   It confirmed my belief that the voice of this community needs to be heard.   Parents, Patients, Siblings.   And that when this voice is raised, people listen.    We will continue to raise these voices next year and the year after that and the year after that.

Breakout sessions.  Caring for an individual with Duchenne is difficult and often requires decisions that we (as parents) never imagined we would be faced with.   Spending time in small sessions, expressing concern, asking questions, learning from experts, assure all of us we are doing our best and more than that, we motivate researchers and clinicians to think out of the box, to understand this critical need.  Amanda Becker said it exactly right in the breakout session on Ataluren.  One father mentioned his son’s ejection fraction dropped 20% after discontinuing Ataluren.  While there is no data to confirm a direct relationship, stopping Ataluren was the only change to his son’s regimen.  As each person expressed their own experience with Ataluren and interest in participating in an access program, Amanda said that in her view any change, any loss of function and surely a change in the ejection fraction constitutes an emergency.  PTC’s medical officer had never thought of Duchenne in that way.  Duchenne is an emergency.

Duchenne Therapeutics Development Meeting (aka –scientific track).   The room was packed and the talks intense, hopeful, promising.  Some parents came away shaking their head and suggesting they were able to understand about 20% of what was said, but very thankful to have the opportunity to attend.   Researchers/Clinicians agreed the meeting was successful, that a Duchenne Therapeutics meeting is important, but said they felt like they missed important sessions with parents.   Parents had to choose and often felt torn, feeling the need to stay informed, but missing out on critical discussions relevant to their son’s life today.    Next year’s plan will definitely include the Duchenne Therapeutics Development Meeting.  We are exploring ideas about how to juggle things around a bit, which probably means adding more time to the meeting.  Stay tuned.

Conference sessions felt nearly perfect – okay, I am biased.  The early breakfast with Industry was informative, on both sides, as companies shared their experiences and addressed concerns.  The plenary session included a broad range of topics, at first general (biomarkers, drug development, clinical trial development, multi-system trials, outcome measures) to very specific strategies such as exon skipping, utrophin, Lam iii, stem cells and viral gene therapy, and various cellular pathways involved in muscle degeneration.

The Levin family threw a lovely barbecue on Friday and by the Saturday gala, I think we were all a little foggy.  The NJ staff had (nearly) killed themselves planning, preparing, and executing the Conference.  Our brains were full of research, clinical care, friendships made and renewed…and HOPE.   We awarded this year’s fellowship to Nick Dobes, who described his relationship with his friend Brian and one more time, we were reminded that our sons’ lives have a ripple effect throughout the community and the world and that all of us play a major role in advancing treatments.  It was always obvious to me, but even more apparent when we are together, when we speak in ONE VOICE, we know we will change the world.

Looking forward to next year…

Sunday nights.

Happens every time. Mom gets on the phone. Some light goes on and your children have a question or problem that needs immediate attention. "Let me call you back."

Same with acute illness. It’s Sunday evening and you wrap up the weekend. And suddenly, your little one complains. Sometimes it is a stomach ache, easily explained by a weekend of activity and a little too much of something. Other times, it is more serious, something you cannot put your finger on, but you have the sense that this is more than you can handle.

On Sunday evening, Jen - a PPMD mom and a friend - called me. Danny was complaining of chest pain. He just celebrated his 8th birthday and in our head, should be too young to connect this with cardiac anything. But then, he has Duchenne and we have learned anything is possible. We have learned that we need to know a lot more than we do about Duchenne hearts. We have learned not to ignore the complaints of our son. While we were on the phone, I could hear Danny cry, but the cry had a little squeak to it and I felt a certain panic creeping in. It was the sound that occurs when people (adults and little ones) make when they are short of breath. We talked about the last few months, rapid progression, weight gain, going off GH and then resuming. We talked about diet, activities, fatigue, increased weakness. Jen mentioned an irregular heartbeat. If I was there, I would wish for a stethoscope or put my ear on his heart in an attempt to diagnose the rhythm. Jen and Dan left for the hospital with Danny.

In the meantime, I called our experts, Linda Cripe, Larry Markham, and Brenda Wong. Linda called immediately. Larry emailed me a bit later. We discussed the events leading up to the chest pain, discussed the last few months. And while this was later considered a ‘cardiac event’ - it was not a heart attack and not congestive heart failure - what did it mean?

The truth of the matter is that we just don’t know. Danny’s troponin levels were elevated. Troponin tests are ordered for people with chest pain, to see if they have had a heart attack or other damage to their heart. Troponin tests are used to detect and evaluate mild to severe heart injury. Normally, cardiac troponin levels are so low that they cannot be measured and in instances where there has been a heart attack, sometimes remain high for 1-2 weeks after. The test is not affected by damage to other muscles. Danny’s troponin levels increased. CK-MB also increased. CK-MB is a more sensitive marker for myocardial injury that total CK activity because it has a lower basal level and a much narrower normal range. CK-MB levels become elevated in 4-6 hours after a heart attack and peak at 10-24 hours. CK-MB measures small, but significant changes during the early hours following onset of chest pain. But here’s what we do not know. We did not have baseline tests. Trophonin and CK-MB are not done with the typical evaluation, so there is no baseline. We don’t know where Danny’s levels started, we simply know they increased. His echocardiogram was unchanged from previous.

What we can say is that Danny had a cardiac event. There was no damage to the heart. Echo was unchanged. And levels decreased.

Here’s the take-away message.

1. Kids (all of them) get sick when we feel least prepared or connected.
2. No matter where you take your son for care, take home information about the hospital’s emergency system. All hospitals have contact information on the doctors – home phone, mobile phone. Cincinnati Children’s is developing a card with exactly this information – it will be given to every patient/family.
3. If you take your son to the ER, ICU, CCU, hospital (anywhere), insist that the doctor connect with his Duchenne doctors. I realize that this request may not sit well with the ER doctor …. Excuses “I treat kids all the time, this is a busy ER, I have heard about Duchenne, I know about steroids,” but this just does not cut it because we know Duchenne is very complex, that there are few experts in the world and likely none at the ER near your home, and that there is significant clinical variability (each child is different). And the heart is a muscle too.
4. Cardiac workshop. We held a cardiac workshop several years ago to discuss what we know, what we need to know, and what we might do now. We are interested in proactive care, hopefully to prevent, slow, or stop dilated cardiomyopathy.
5. Advocacy. We are working on a pilot telemedicine project – hub and spoke – to connect experts to families /doctors. As clinical trials open in the US and elsewhere, close connections need to be in place for those very late nights.

Danny is home now. There are still answers Jen and Dan are waiting on. But Danny is okay, his parents are okay, and we will keep doing what we can to share any pertinent information with you.

Reversing the question – parents helping children; children helping parents. Is there a middle?

I just returned from a meeting in Europe and one of the best things about these meetings is hearing stories of families, listening to experiences, and learning about those special times when a child’s insight makes us stop in our tracks. It is not about criticism or what is wrong, right, or in between. It is just about those times when we find our hearts’ making a recording that we will remember all the days of our life.

One mom talked about all the things she was doing for her son. She described a pretty time consuming schedule that included supplements, stretching exercises, aqua therapy, as well as a very strict diet. It was pretty amazing really and I had the sense that she had achieved the perfect “10” as a mom, someone we would all look up to and wonder just how she fits everything into a 24-hour period or if she found some magic to stretch the few hours in a day. All of a sudden in the middle of her story, she had tears in her eyes as she talked about one particular evening when her son was grumpy as she started the stretching exercises. He had had a full day. As she started his stretches, he started crying. She asked if the stretch was painful. He said ‘no.’ Like all of us, she probed, asking if something went wrong at school, if his stomach was upset, if he was in pain, looking for something, anything to understand the tears. We have a natural tendency to try to ‘fix’ everything. He simply said he did not want to do the stretching tonight. With that, her fear increased and she tried to sooth him, tell him how important this was for his muscles, how much she was doing to help him. And in that very simple way that children have, he said, “You are not doing this for me, I am doing this for you.” She felt her heart breaking.

I also spoke with a father whose son is now in college. He discussed his son’s detailed agenda to include a variety of interventions squeezed in between college classes and studies. I asked about friends, about movies, about music, about laughter. This father said all that would come later. I wondered when ‘later’ was planned. This father was so worried that if something interrupted their rigid schedule, his son would lose function. He felt this regimen was essential to maintain the life his son had, the things his son was able to do at this very moment. One glitch, one change, and it would fall apart.

I remember hanging on for dear life, thinking that if I changed one thing, if I took time to breathe, time off, time to enjoy something or some activity from my previous life, things would fall apart. It felt like my life was hanging on a thread. I remember hanging everything on the future. I started sentences with ‘when this happens,’ thinking that a certain clinical trial would yield amazing results and then we would catch up on whatever it was that we missed.

Every once in a while, I think it is good to take a step back and remember, the life we are living is not a dress rehearsal, it is the real deal. There are no ‘do overs’ and no way to recover time lost. So, while we are all aggressively pursuing what we think is the best route for our sons and daughters, it is important to listen to their voice, to ensure the discipline of care includes their perspective and their opinions.

And as you make up the schedule, please include 30 minutes of laughter. It should be considered a therapeutic intervention!

Washington Week in Review

Did I miss Spring?    I spent the last week of May in Washington, DC.    I had meetings on Monday and Tuesday centered around regulatory issues (FDA and OOPD), compounds, small clinical trials, webinars, and workshops in the planning stages and tossing around some ideas about how to design new models for trials, or how we might encourage companies to think a bit outside the box.   Discussions like this are like taking a breath of fresh air into your lungs.  I find them invigorating, hopeful, and promising, incredibly thankful to see the results of our early investments in research now move from the bench to the bedside .   On the other side, I realize nothing will ever move fast enough for our boys.    

By midweek, the conversation changed slightly to include the range of interest, opportunities, and programs focused around  Rare Diseases (R.A.R.E,  Every Life Foundation,  Rare Disease Caucus, GrandRx, Cure the Process, etc), how the Rare Disease Community is focused on developing tools to streamline the drug development process for rare disease and the worldwide focus on RARE. 

At the end of the week, I participated in my last face-to-face meeting with the Institute of Medicine Committee.   I have been serving on this committee for the last year.   While some of the committee members knew each other in a past life, the charge of this committee was new and quite daunting.  We were  charged with writing a comprehensive paper on Accelerating Rare Disease Research and Product Development in Rare Diseases and writing recommendations that are expected to result  in legislation.  This experience has been intimidating, amazing, and wonderful all at the same time.   The committee is comprised of individuals representing a  broad range of expertise –academia (clinical trial experts, epidemiology, rare disease), researchers, venture capital,  drug/device executives, attorneys, and  foundations.   This last meeting was bittersweet. We came to the end of our investigation, reporting progress to date and making recommendations for changes that we hope will positively impact the trajectory of treatments and cures.   For me, it was a incredible learning experience, to systematically go through what we now know about rare disease, what we need to know, what tools need to be developed, what processes need to be streamlined, and where resources would be useful.  What was even more moving was to understand that each member of the committee had been impacted by a rare disease, that each member understood how rare disease isolates, how rare disease impacts individuals, and how we, as a country might work together to break barriers that get in the way.

 The report is expected to be published this Fall.

Ataluren Update

As many of you know, because you participated, PTC held an open conference call yesterday to update the community about ataluren and future plans. The discussion included analysis of data from the ataluren trial and a summary of regulatory challenges. Langdon Miller (Chief Medical Officer for the trial) described PTC’s plan for regulatory interactions relating to ataluren and the effects of these interactions on potential patient access to ataluren.

And when the call was over, like many of you, I walked away from the call still frustrated, still hurting for our boys.

I understand the urgency to complete the sub-analysis and to prepare the package to establish the path forward.  Like you, I worried we would again be waiting until  the presentation in Naples and another call. 

Time.  And like you, I have watched my own two sons lose strength and felt my heart break over and over again for them and for all of you.

I reviewed this conversation in my head throughout the night and today.  I wanted to have something concrete to hold onto and step-by-step I went through the call.  And I made some calls.

Here is what I understand: 

By the Naples meeting PTC will have completed the analysis and prepared the package for the regulatory path ahead.  Keep in mind, while on the call, PTC talked about an access program and mentioned Individual IND’s.   I think the risk/benefit of the individual IND is worth pursuing as each day these boys lose function.  You already know, I think in increments of 5 minutes:  treasuring every one of those moments and hoping to buy more.  I know all of you feel the same.

This morning I spoke with PTC and asked that question in order to get some details and clarification.  PTC confirmed that they are planning for individual IND’s.  Planning is being done in parallel to data analysis and preparing the regulatory package.    PTC is interested in understanding who/how many of the families are interested in securing an individual IND.  Please contact your site coordinator and ask if they would be willing to participate in an individual IND.  

I know what you are thinking, that you may have another willing physician.  At the moment, PTC wants to understand:

1. Who is interested in an individual IND, and
2. If the physician from your  clinical site would be willing to act as the sponsor.

Please send this information to Diane Goetz. 

From the FDA SITE: The sponsor is the person who takes responsibility for and initiates a clinical investigation. The sponsor may be a pharmaceutical company, a private or academic organization, or an individual. A Sponsor-Investigator is an individual who both initiates and conducts a clinical investigation and under whose immediate direction the investigational drug is being administered or dispensed. For administrative reasons, only one individual should be designated as sponsor.

I feel – PPMD feels – that it is our job to tell your stories to PTC and any other company working in Duchenne.  And we will.

I have said it before – I continue to believe in the work of PTC. I believe they are committed to helping our sons and I truly credit them with being trailblazers in Duchenne treatment.  I also commend them for their communication with us. Most pharmaceutical companies would remain silent in a situation like this and while we may be frustrated by the information we receive or the amount of information we have received, at least we are not listening to silence.  

But we won’t sit still and we won’t sit quietly. 

Week in Review: 4/11-4/15

I spent the better part of the week in Washington, DC with a full agenda. On Monday, I met with Peter Saltonstall (president of NORD). One of NORD’s major interests is the FDA. You are probably familiar with our advocacy agenda, this year concentrating on several areas relevant to clinical trials – one very specifically directed toward FDA. One of our requests focused on securing additional resources for the FDA, specifically more expertise and experience on rare disease (Duchenne), communication, and collaboration with the orphan products division and efforts to harmonize interaction between EMEA (European regulatory agencies) and FDA. NORD is focused on the same issues and when voices join together with specific messages, things happen. Anne Pariser, MD is now the Associate Director of Rare Disease, a new position with FDA.

On Monday evening, I served on a NORD panel to discuss barriers facing therapies for rare diseases. I spent some time discussing barriers such as risk benefit (such as asking for definitions of risk when the condition is fatal) and discussing TIME (how minutes matter when, in progressive conditions, each minute represents cell degeneration and death). Time. Loss of function. Lost time with someone you love. And steady state. How many times have we all prayed, that Duchenne stops now. Today. Steady state, no further degeneration.

On Tuesday I met with Anne Pariser. Anne has worked for the FDA for over 10 years, working in the area of inborn errors of metabolism. She is wonderful and anxious to accelerate therapies for rare disease. We discussed exon skipping and meetings planned for Fall. And I took a left turn in the conversation. You may already be aware, NIH (NINDS/John Porter/Berch Griggs/Katie Bushby-Treat NMD) have been awarded a
grant for a multi-site steroid trial. The trial will have several arms, evaluating an intermittent regimen with daily
Deflazacort and daily Prednisone. Makes no sense to me unless, at the end of the day, should the data suggest Deflazacort has less side effects (weight gain/behavior) it would be available (and covered by insurance) for families in the US. Anne said she had no knowledge of the trial. Now she does. And John Porter is connected to Dr. Pariser. And those planning the trial are connected to Dr. Pariser and to Elizabeth McNeil (orphan products). One of the goals of this study will be to (FINALLY) have Deflazacort available and approved in the US and hopefully elsewhere. Families deserve choices…and trials must consider access to whatever they are testing. Families already have significant financial burden in Duchenne. ALL therapies must be available and ALL boys must have access without additional expense.

Wednesday and Thursday I was in closed meetings with the Institute of Medicine (IOM). Our task is to produce a report (Fall, 2010) on “Accelerating Rare Disease Research and Orphan Product Development.” The report will include discussions and recommendations on discovery, drug development, FDA, the Clinical trial process, insurance, Medicare/Medicaid and devices. You might be aware of Senator Spector’s CAN legislation – $500 million for rare disease. Cross fingers and pray this legislation becomes law.

Progress!

Albania

During the Connect Conference last year, I was invited to speak in Albania. It is hard to say no to invitations during the Conference because the need is so clear and the impact of information so evident. So, I said yes…knowing it would be sometime in the future and maybe, depending on the circumstances, might not happen. In January, Mira contacted me reminding me of our conversation and the scheduled date, March 27. In January, the end of March seemed far away.

I met Mira some years ago. This is a story we all know well. While Mira is a neurologist, she does not see individuals with Duchenne, rather only one, her friend’s son. He was diagnosed at six. No intervention recommended. None. Therapeutic nihilism.

He started steroids at the age of 18. Mira attended our conference in Philadelphia, coming back year after year. She delivered information and advice to the family, and this young man’s quality of life improved. She learned how to buy time. At 24 years old, his echocardiogram is stable. He is on steroids, ace inihibitors, beta blockers, supplements, swims three times/week, works for his father, and enjoys spending time with his friends. For this one young man, life is good.

On March 26, I arrived in Albania. The airport was small and as I watched the luggage arrive in baggage claim, I had the sinking feeling that mine had not made the connection from Rome. With only one flight/day from Rome to Tirana, there was no chance of clean clothes anytime soon. I had been traveling for 20 hours or so and looked it! Wrinkled clothes, bad hair, and no makeup! I was scheduled to speak early Saturday AM during the Albanian Neurology Conference. Thanks to Mira’s influence, this year was focused on Duchenne. Several Coke Zero’s (could not find a Diet Coke anywhere!) later and life improved.

Mira and I went out for lunch and a short history lesson about Albania. The communists were defeated just 20 years ago. The communists’ occupation included confiscating homes, tearing down churches, persecuting religious beliefs, taking away freedom, and crushing dreams. Medical care remains under government control. Patients are able to see their doctors, but there is little access to medicines. Rare disease... well, better not to have a rare disease in Albania.

A pause. The country of Albania is beautiful. Flying in, the 60,000 ft. view is lovely. Tirana is surrounded by mountains and bordered on the West and South by the Sea. On the ground, the people are warm, friendly, and kind. But I did see something else and maybe it was best characterized by the lovely young woman that interviewed me. We talked about Duchenne and about Albania. She said, "We try but dreams of change feel impossible, a mountain too difficult to climb."

The meetings started at 8:30AM and most of the talks were in Albanian. Doctors from around the country attended the meeting as well as neighboring countries such as Kosovo. The neurologist who cares for individuals with Duchenne spoke just before me. A kind, young doctor was sitting next to me, translating phrases, though as I stared at the slides, I understood. I closed my eyes and was back in 1984. The slides on the diagnostic workup hit a nerve –clinical presentation, EMG…. EMG! It was 1984, Children’s Hospital Cincinnati. I was standing next to my beautiful son Patrick. He was 4, with his blue eyes open wide and tears falling, “Mom, make them stop” and a frustrated technician telling him to grow up. EMG means sticking needles in a nerve to measure conduction. It was horrifying then and now. In 1984, EMG was done on Duchenne. I’ll never understand why or how EMG was included in the diagnostic workup and I screamed at the tech and later the neurologist. I did not understand the rationale then and certainly not now.

But today, at this meeting in Albania, EMG was included on the slide. I thought I was tired, misread the slide. The neurologist then described their genetic testing capability, that approximately 60% of the mutations were identified. What about the rest? Recommendations for steroid use are limited to an intermittent regime. There is no registry in Albania, no access to sequencing, no thought of clinical trials. One neurologist commented “you are the first parent I have ever met.” I’m certain he meant that I was the first parent ever to speak to physicians. My talk focused around “who’s actually in charge… the doctor who sees the patient for a short time, say 2 hours/year or the patient/family who spend around 8700 hours together each year?...” As part of the Q&A, I was asked about care in the US and answered step by step: no EMG, clinical diagnosis, genetic testing (full sequencing), steroids – and on and on and on.

This was my first trip to the region and while I recall hearing sound bites of information about communist oppression in the Balkans, I did not realize the real impact. While I cannot walk in their shoes, I learned from being there, from the stories. The communist presence is still felt. The Albanian people are rebuilding, but slowly. They lack educational opportunities and infrastructure. There are remnants of communism in healthcare, doctors who deliver the ‘no hope and no help’ messages. There are remnants of communism throughout the country, in buildings and in empty spaces, where homes, churches, and businesses used to exist. There are remnants of communism in the mentality of the people, perhaps reluctant to dream that things might be different. And there are pockets of strikingly beautiful areas everywhere, storybook places, where new dreams are planted.

And, as Duchenne connects all of us, together we will fertilize and help to nourish those young plants so that boys in Albania will have opportunities and dreams.

GSK & PTC Updates

GSK

First off, a qualifier. If you are reading this for inside information, such as the start date of the trial, the protocol, the willingness (or not) to consider compassionate use, etc., stop reading right now.

We (Sharon Hesterlee, Kimberly Galberaith, and I) met the GSK team and while all of those thoughts were on our mind, we knew that those were not the questions to ask and that we were not meeting for the purpose of asking for confidential information in an effort to leak it to the greater community. Rather we were meeting to think about how we might work together to support and accelerate trials (and hopefully treatments) for our sons.

The GSK folks we met with consisted of the people involved in scientific communications, global commercial strategy, alliance development, and public policy. We went into this meeting without an agenda. We felt a synergy the moment we met and the conversation flowed from there, covering a range of topics to include urgency, high unmet need, anticipation, and expectations. We discussed the GSK relationship with Prosensa and the capability and capacity they bring to the table. It was obvious that GSK is committed to Duchenne. It felt good to see their interest in Duchenne, their openness to new opportunities, and here’s the thing...having GSK (better known as ‘big pharma’) onboard is quite a coup to be honest. These folks know the ropes, they have experience in taking drugs through the clinical process and to market.

We spent some time talking about the individuals and families who do not fit into the current antisense compounds (rare deletions, duplications), how the community feels fragmented based on mutations, as if, for some boys, there is less hope than for others. We talked about the fragility of the community, the increased frustration and desperation as strength decreases and walking is threatened. They understood, perhaps not to the degree of parents/families watching minute by minute, but the message was heard loud and clear. We spent a good bit of time discussing the need for a regular communications plan, a website where all foundations/organizations would direct interested individuals: the one-stop shopping for accurate information and consistent messaging, so that information does not arrive in sound bites or tidbits of information from anyone, rather information we all can count on to be accurate. We learned that while this sounds easy on some level, there are loads of hoops before information is released and SEC and regulatory concerns that need to be considered, such as communication that might suggest results or promise, or anything that can be perceived as persuasive in terms of trial recruitment.

We discussed clinical sites and whether more with fewer patients is better or less with more patients might produce better data with less variability. We discussed using clinical sites with expertise and experience (and trust by the community) in Duchenne AND with clinical trial experience.

We discussed their commitment. And while it is true, none of the people we met with have a child with Duchenne, they all have a story about their interest in medicine, the soundtrack of their lives where the twists and turns of their careers brought them to this place, this world of Duchenne. And they seemed happy to be here, dedicated to making a difference and joined the ‘church’ of believers, that Duchenne can and will have treatments.

As you might imagine, we left with that same laundry list of questions in our head, but respected the fact that data would become public during the AAN meeting. We discussed protocols, asked if they would consider expanded access or compassion and the ever present “WHEN” question. No answers at the moment and all possibilities are in discussion.

GSK/Prosensa will release data from the European trial during the upcoming AAN meeting, April 12-17 i in Toronto. Exact date is April 15. Stay tuned.

PTC

Same qualifier as above. If you are looking for sub-analysis data and next steps, stop reading.

Later the same day, we met with Stuart Peltz, Langdon Miller, Theresa Nalatacchio, and Diane Goetz. Fatigue was obvious as the analysis continues. You all already know, I think the PTC folks are what my mother calls “good people.” I have known Stu Peltz for 7 years. He is committed to Duchenne. He is a fighter. With his team he is sorting the data, sifting through to see the path forward. They believe there is a path and I think this coincides with the community’s belief. It isn’t easy and the path is not crystal clear at this moment as they weight the arguments and plans for moving forward.

We discussed the fact that the community feels like the rug has been pulled out from under, that the messaging from the clinical sites varying and frustrating, that parents are worried about what happens physically and psychologically as the drug/compound is stopped. And that frustration has turned to anger and there is no place to put the anger. Stu and his colleagues understand.

I guess that’s hard to imagine from where you sit, but it was quite obvious on their faces. This was not the plan. PTC has been the pioneer, the oldest child (in a manner of speaking) trying to carve a path forward in the best way possible, with a community that has not participated in registration trials, a community that does not have rigorous natural history data, a community with high unmet medical needs, and a sense of urgency that is hard to actually put into words. An urgency that makes a parents’ blood flow feel like lava when their child falls, or stops walking, or worse.

I believe in PTC and believe that they are working very hard to develop a plan for success. We talked about access programs, about compassion, and talked about Genzyme’s program. I was surprised to learn that Genzyme’s program for expanded access involved less than 5 people. PTC has 200 +/- boys who have participated in trials to consider as they plan next steps. They are listening. But at the same time, they need to succeed, otherwise even expanded use or compassionate use would come to a stop.

Ataluren needs a path forward, so that all boys who could likely benefit, have access to that opportunity.

Katrina Revisited

I don’t know about you but I felt last week the Duchenne community was hit with our own hurricane, similar to the 5^th deadliest hurricane in US history, 2005 Katrina. I’m not from New Orleans, but have a good friend, Diane, whose home was washed way when the levee system failed and neighboring parishes flooded. The 175 mile winds took everything - house, furniture, photos, memories, life as she knew it. While nearly 2,000 people lost their lives, her family managed to survive. She was in Cincinnati at the time, desperately seeking information and connections to those she loved. I could not imagine how she felt during that time, but saw it on her face: pain, desperation, sadness.

I cannot relate to Katrina, but on Saturday I felt like I was seeing the aftermath of our own ‘hurricane.’ The wind died down and the reality hit. As a community, we were left in the aftermath, trying to makes sense of the news, trying to find some meaning, some hope.

I have been following the discussions, the criticism, the sadness . These trial results are not what we expected or wanted. We all wanted a win for Duchenne. We depended on it as if it would feel like a neon sign that this one win would lead to more, would mean the stars were lining up just right. And sometimes when we hear bad news, everything else in the world looks bleak.

I must have asked Tom how he was feeling a million times, thinking the universe must be against us. Finally he told me I was simply not allowed to ask. I went to the nursing home to see my mother and this sweet 94-year-old German Catholic woman who taught me that "life is not a rehearsal and while you may not be able to control the boulders thrown in your path, you will find a way to walk around, over or compensate for them”; this lovely woman looked at me with tears in her eyes and said that ‘they’ were giving her pills to hurt her and there was no way to reason with her. She was afraid and I could not convince her that I knew what pills she was taking, that I was in contact with the doctors, that I would keep her safe. Senile dementia. I left feeling defeated, helpless. And my daughter Michelle moved into her new flat in London (Primrose Hill, Princess Lane), the boiler failed, and she had no heat or hot water. At that moment, I wanted to fly to London and bring her home to my safe house. (If you were to meet some of my relatives, you would understand that they typically do not allow children to move far from home). I called my other daughter Jenny to make sure she was safe. I had no reason to doubt it, but it felt like the universe had changed on its axis.

The discussions on the website reflect anger and sadness. We are all grieving. Discussions related to trial design – was it the right design? Was the 6 Minute Walk Test (6MWT) the best or worst choice as an outcome measure? How do you measure benefit in a population where clinical variability (function, progression, cognition) are highly variable? Should the stratification of the trial have been more precise as in eliminating boys who could not walk a certain distance (<350m) in the 6MWT? Too many sites/wrong sites? How much dystrophin expressed? What are the individual responses? Why can’t you change course in the middle of a trial? Do something different? Why suspend all trials? What about compassion? And what next?

I find the criticism and the desire to point the finger at someone or something incredibly sad and a bit overwhelming. I understand it as I have been angry since Duchenne entered my home, my vocabulary, my every thought. But it is DUCHENNE I hate, not the people. I thought about my own life and the decisions I have made and how with additional information, I might have made different decisions. I have made good decisions, bad decisions, ‘meh’ decisions (those are not so important decisions), and have had the opportunity to revise and re-do and some of the time, rethinking and redoing has improved the original decision by leaps and bounds. Pity that we don’t have a crystal ball.

On Saturday I received a call from a mom who had been contacted by another mom, whose son was not in the trial. The description of the call was sad – pointing the finger, criticizing people, recommending litigation. I was at first angry and then sadness fell on me like a wet blanket.

After that unsettling call, I drove to the Dorothy Lane Market in Dayton. I bought 3 way too expensive cookies (Laura’s large sugar cookies @ $3.00 per). If I was in New York, I would have gone to the Magnolia Bakery for cupcakes, but I was in Middletown, so the choices were limited. I ate all 3! I think it took less than 5 minutes to consume all of them, what may be upwards of a total of 3000 calories. While they were going down, I loved it. I thought it was perhaps the best investment ever. Then I went to my favorite shop in Hyde Park and tried on pants for summer. I could not button them at the waist and the way they looked in the mirror did not fit with the image I had in my head. So I left. In retrospect, I should not have eaten the cookies, should not have stopped running after freezing my bottom off in Florida in January, and should not have York Peppermint Patties sitting on my desk. Bad decisions and if I could get a do-over, I might make other choices.

Divorce/partners –another example. You marry your partner because it looks like a good decision at the time. Over time you learn more, life throws in a few boulders, and you find you need to make a different decision. And you do and the second time around it is sometimes better. Different factors, new knowledge, experience, wisdom. Your primary endpoint changed? Secondary endpoints different?

All this is trivial in light of a clinical trial that may mean the difference between maintaining/improving function or not and extending the length of life. But in some strange way, there are similarities. Decisions are made based on knowledge at the time. Trials are developed with advice and expertise from a range of individuals to include parents/patients – experts ( specific disease process, drug development, regulatory, business model, etc) and with all of that in mind, trials are conducted and data analyzed. The data informs and based on recommendations (in this case) the trial is suspended. Keep in mind, SUSPENDED is not ENDED. SUSPENDED to regroup, rethink, analyze, and clear the path forward.

I hear the phrase "compassionate use", but the case (based on current data primary /secondary outcomes) is not there.

So, we have to wait. Wait for sub-analysis. Wait for the plan. And once the path is developed, we will do whatever it takes to move toward success. Like you, I have heard the anecdotal stories –both positive and negative. I remain a believer –that Duchenne will have treatments and in the near future, that suppression of premature stops is a promising strategy. That exon skipping, utrophin upregulation, myostatin inhibition,
increasing nNOS – are all potentially promising.

But I am not ready to throw arrows at anyone or anything...except Duchenne.

We are all reeling in the aftermath of our first (and hopefully only) hurricane. We have all fallen apart in our own ways. Let’sgather, like my friend, go back and sift through what we have learned and moveforward together. Stu Peltz and everyone at PTC are committed to our sons. There is a way forward and we will find it.

P.S. Diane sorted through the rubble and found a picture of her dad in perfect condition.

Ataluren Results

Yesterday was really difficult.

In 1999 our Scientific Director Lee Sweeney published an article on Gentamycin and while that was good news, we knew Gentamycin could not be a lifelong therapy. Then PTC marched into our lives, committing time, talent, and millions of dollars. They paved a road where none had been before. They became friends, invested in our community and our sons.

Over the years, we watched as the words premature stop and PTC124 nearly became household words. We found ourselves hanging our heart on the concept of the first treatment for Duchenne, if only for a subset, knowing that we would do whatever it takes to expand our horizons until every boy had a treatment. PTC developed and executed the first pivotal study of a New Chemical Entity (NCE) in Duchenne.

This is a huge step in and of itself, recruitment completed two months ahead of schedule. Parents/families, physicians, industry all coming together from around the world. Duchenne was studied in a systematic way and more thoroughly than ever before.

The outcome we have received is devastating and the news yesterday threw all of us over the edge. This blow knocked the breath out of all of us and at least for a moment, some of the wind out of our sails. PTC will further analyze the data and we will learn more about the results and the trial.

I’m still hopeful we will see some light and with that, a path forward. Regardless, we are still believers in our sons, in our community, and in PTC.. There will be treatments for Duchenne and we will find them. That is certain. PTC has been building the road and will continue. They are not changing their commitment to our sons. They are acting in our best interests and will continue to stay focused on the road forward.

I just wish the road was a bit easier and without so many damn boulders.

The "Female" Side of Duchenne

It was a long time ago that I sat in the exam room and received the diagnosis. My boys had Duchenne. The diagnosis was followed by a series of questions about my family history, the doctor assuming that somewhere along the line, there was another boy long ago. In my case, there was no history. None. I asked every living member of my mother’s family what they knew, if there was someone who had an unnamed ‘problem’, someone who was weak, or a child who died young from an unnamed illness. One of my cousins talked about my "crazy Uncle Harry” who fell off the roof, but it hardly fit the picture I was looking for. I had a brother Jack, who died young, at the age of 42. A heart attack after jogging. He was my closest friend and I wondered if he might have had a mild form of Duchenne – decent muscle strength, but severe cardiomyopathy. It was always a question.

I guess it would have been easier to simply test my mother, but she had her own issues with the diagnosis. Catholic guilt. She had the sense that a god would punish her for past deeds and I did not want to create additional burden for her. I left it alone, an open wound. For years, I wondered. In retrospect, I wonder if I just wanted to be able to point the finger at someone else. I didn’t want to be the first carrier, the de novo mutation in my family. It seemed so unfair and it felt like I did something wrong somehow. OK, intellectually, I realize, spontaneous mutations occur frequently. The dystrophin gene is particularly susceptible based on its large size. Eric Hoffman suggests 1:10,000 egg and sperm cells carry the mutation as a new event. Random. Right, but emotionally it still hurts. Motherhood and guilt.

Just before the FACES meeting in Colorado, we met with Ivy Scherbarth and Angela Knight. It is always a question. Are you a carrier?. We discussed and compared carrier vs non carrier. Ivy had tears in her eyes as she had looked back through her family, tracing what must have been Duchenne generations back. Angela, not a carrier, said that either way, having a child diagnosed with a genetic disease is accompanied by guilt. I think she’s right. There is no way and no need to compare the feelings. Mom’s feel responsible. But there are more questions and strings attached to the word “Carrier” and the word stings somehow, sometimes feels like an indictment, with questions about prior knowledge, muscle weakness and concerns about the risk heart disease.

Carriers are working on two dystrophin genes, one carrying the mutation and one without. And we are hopeful that our cells opt to use the “good” gene, the gene that does not carry the mutation, producing normal quantities of dystrophin in every muscle and tissue of our bodies. But sometimes it does not work that way. When moms talk about this openly, some share stories of muscle cramps, weakness, fatigue. One mom recently mentioned she had a weak handshake and her doctor thought it was characteristic of a carrier. That sounds a little over the top to me as handshakes are personal, dictated by much more than muscle strength. I think the answer may be somewhere in the middle. Some moms have weakness ranging from mild to severe. These moms are referred to as ‘manifesting carriers’, their cells opting to utilize the genetic recipe for dystrophin that is inaccurate, incomplete. This is referred to as X-linked inactivation, where the cells essentially turn off the ‘good’ gene with the accurate recipe for dystrophin. And, depending on the degree of the X-linked inactivation, there will be weakness, from cramping to weakness to loss of function, sometimes severe.

Carrier moms also need to take care of their heart. Statistics suggest that 10% of female carriers are at risk. I’m not sure where that statistic comes from. I have seen some papers suggesting the risk is greater. To be honest, I think the statistic is not important as the fact that we need to take care of ourselves. As moms, we often ignore our health to take care of our family. How we feel is last on our list as long as we are getting out of bed and managing to get through the day. I think all women need to pay attention to their heart. Heart disease is common in women and it is essential that we keep our hearts beating strong for ourselves and for everyone who depends on us. Carrier or not – take care of your heart.

And girls with Duchenne. If a young man with Duchenne married a carrier of Duchenne, it is possible that they could have a daughter with Duchenne. I would guess this is indeed very rare. But it could happen. For the most part, girls with Duchenne have X-linked inactivation, where the cells turn off the normal or ‘good’ dystrophin gene. Depending on the degree of this X-linked inactivation, their progression could be the same as a boy with Duchenne. Because Duchenne affects boys 99% of the time, we talk about Duchenne in male terms. Every photo you see will show a boy. In the US, we are guessing around 10-15 girls have Duchenne. While Duchenne is not a club you want to join, I cannot imagine how it feels to be in the club but feel that you are standing in the back of the crowd, unnoticed.

I think this is a discussion we need to have – Carriers, manifesting carriers, girls with Duchenne. If you have any ideas about this, please let me know. You can always email me at Pat@parentprojectmd.org.

And to end my own personal story. I did have my mother tested just last year, assuming in my heart that she would be a carrier as well. She was not.

My father’s company manufactured Doctor bags, the old time doctor bags you may have seen in films. To this day, they are called “Schell bags”. Every Sunday, I would ride with him into town, to the factory (Schell Leather Goods) where he would light the glue pots, so that by Monday, when the men working in the factory arrived, the glue would have reached the appropriate temperature for the leather to adhere to the wood frame. I remember a strange sweet smell wafting through the plant after a few minutes. In conversations with other carriers, some mentioned that their fathers worked with chemicals – fertilizers, pesticides, stuff.

I’ll always wonder. It’s human nature. 

Watching From Israel

Duchenne Israel held its first conference on Tuesday evening. Professor Yoram Nevo, the leading pediatric neurologist and CINRG director opened the meeting with a discussion about his efforts to combine Losartin and Copaxone as a potential substitute for steroids. He has data on each compound and will now test the combination in the mdx mouse. 60+ family members, doctors, researchers, and healthcare professionals attended the meeting. The room was filled – over 60 family members, doctors, researchers and healthcare professionals gathered together for this meeting. The room was filled with excitement, with community, with hope. This is my first trip to Israel and as I stood on that podium, I saw the diversity in the room –different cultures, different belief systems – united in the universal language called Duchenne muscular dystrophy. It was exactly right. We should be together, working side by side.

This afternoon my wonderful hosts took me to the Wailing Wall and to the tunnels, the excavation site to expose the entire Western Wall. Our tour guide provided the historical prospective. We looked back in order to look forward. As we climbed down into the tunnels, the guide explained we were in the central part of the Western Wall, the place thought to be nearest to the Holy of Holy places. We stopped there in prayer, wrote names of the young men we lost this year and placed the notes into the wall.

We walked down the Via Dolorosa, the path Jesus carried His cross. We touched the stone where his body was placed after He died. We again prayed for all of our sons and daughters. We prayed for all of us. Israel. Faith. Hope.

Today is the last day to vote for PPMD in the Chase Community Giving challenge on Facebook. I have voted for Duchenne, for my own sons and for yours. We may not win the $1 million grand prize, but we must vote so that the Facebook universe understands how important our fight is. And so that our children understand how precious we think they are. This contest was never about a big cash prize (sure that would be great, we'll never turn down $1 million!) - it's about awareness.

I'm on the other side of the world from most of you and the faces of Duchenne are just as beautiful here as they are back in the States. Your vote for PPMD and Darius Goes West (another Duchenne specific organization that shares our mission to end Duchenne) is not just for your son or your friend's son, but for the young people all around this world living with Duchenne.

The Marathons of Life

On January 9, I ran the Disney ½ marathon in Orlando. Well, ‘run’ may be a loose term, I walked, but I walked fast enough to complete the race in the required time, crossing the finish line, greeted by a wonderful volunteer holding the coveted Donald Duck medal. It was my third marathon.

I started walk/running in 1984, just after the word Duchenne entered my vocabulary. I was running for something, my own private marathon. I walked for my sons. I wanted to take steps for them, wanted to make up for the steps they would not take and wanted to take steps for others as well. I didn’t calculate how many steps that might take, but I knew that after taking one step, I would be able to continue the momentum.

And now, my private marathons are public, are part of something much larger than myself, something that belongs to all of us. I’m a believer.

55,000 people were running those races in Disney. 55,000 running for something or someone they care about, something or someone they are committed to. 55,000 people committed to succeed.

There is another marathon, but this time, it does not involve running. This uses no energy and with one single click on the computer, will help change the world for 250,000 boys with Duchenne and a few girls and millions of people who love them.

PPMD recently was announced as a finalist in the Chase Community Giving challenge on Facebook. Over 500,000 organizations competed for 100 finalist slots and a $25,000 prize. You voted, and we made it! Now these 100 organizations will compete for five $100,000 prizes and one grand prize of $1 million.

So we need you to vote. And we need you to tell everyone you know on Facebook to vote. And we need you to get everyone who is not on Facebook, to join Facebook, and then vote. The power your one vote could have is incredible. That vote could mean $1 million for Duchenne research. That vote could buy us time.

1 vote. 1 minute. $1 million for Duchenne research.

And if you have 5 minutes we have a list of super easy, super effective ways you can reach as many people on Facebook and have them cast their vote for PPMD. We need all the support on Facebook we can get. Every vote counts!

I am not a seasoned athlete, but I am always able to finish because of the energy of those around me. That energy, YOUR energy, will help us win $1 million to be used in the fight to end Duchenne.

I hope you'll vote today. No training required.

Staying the Course

2010, January

As I spend time on the community site and Facebook, I feel a little jittery. Expectations are high. Everyone is counting days and everyone seems to have a different calendar, a different opinion, and a different bit of information. Some have contacted a clinical center, asking how to get their son in a certain trial, wishing to be first in line. Others have gotten less than expert opinions on genetic testing and the potential ability to participate in an upcoming trial.

This week we have had a number of calls from parents, worried about what is happening with regard to antisense trials and always the ‘when’ question.

The words are familiar – clinical trials, exon skipping (51, 44), first quarter 2010, name dropping of potential sites, conversations with doctors or clinical coordinators followed by a cryptic report on the community site or Facebook. Fear, frustration, disappointment, anger, panic – all wrapped up into one. TIME seems to be slipping away while you are waiting… waiting. The Google alerts are rampant, but it seems there is silence on the exon skipping front, specifically the news you are waiting to hear. And when there is silence, we tend to fill in the blanks… ‘What if something is wrong’, ‘did the company make different decisions’, ‘problems with ???’. Worries increase, tears flow, and the world looks pretty dark. We never simply stop and think – they are working nonstop, need no distractions, and are on track. Once Duchenne enters our lives, we live waiting for the next shoe to drop.

As a community we really need to hold it together and try our best not to over think things.

Prosensa is moving forward. You are already aware of the GSK deal. This is amazing news, exactly what is needed and required for progress. Having GSK as a partner expands opportunities, may change the landscape a bit, but does not change the direction. They are still moving forward. Trials are in development. Discussions with FDA (EMEA) are ongoing. The commitment is solid.

Do not jump with every comment or every post. It is easy to say and very hard to do. Because you are not hearing from someone frequently does not mean the Prosensa/GSK folks are distracted. Be thankful. They are working nonstop to move these compounds forward. They are aware of this great need, very aware that our sons (and some daughters) have no time to wait. They ‘get’ this. This makes every step critical to ensure that the trials are successful and the therapies become approved and everyone who stands to benefit from the compound will have access.

I hear all of you saying – we are willing to take the risk. And I understand that statement, but down deep in your heart there is a follow-up comment – “as long as nothing happens to my son.”

I’m not saying to have patience. That word went out the window with the diagnosis of Duchenne. I’m saying, do not panic. Prosensa, AVI, BioMarin, PTC Therapeutics and many others are all committed to moving as fast as possible and silence should suggest Focus and Commitment.

Last evening Dr Giles Campion, Chief Medical Officer for Prosensa wrote:

Dear Pat

Just tell them that on the authority of the Chief Medical Officer for Prosensa and a member of the GSK Joint Project Team you have it that there is no question of delaying the trial until 2011, on the contrary, everyone on the team is working very hard to run the necessary clinical study as soon as possible.

Regards,
Giles

Stay the Course. 2010 will be a good year for Duchenne.

Aligning the Stars

PPMD is growing. We have an amazing Board, an equally amazing staff (commonly referred to as the Cult), and a wonderful community. So what should be the logical next step? This has been our conversation for the last year. It is easy right? Add staff. But as you begin to think of who that person might be, you start to develop a wish list, naming all of the qualities/skills you are hoping to find in a person. And then there is Duchenne. How do you explain Duchenne to someone who has no experience? It is not an easy subject and certainly not simple. This means, the wish list expands to find someone with a passion for Duchenne, someone who understands the need to buy TIME, someone with significant experience and knowledge about research, someone who ‘gets it’, understands the full impact of the diagnosis. Someone like Sharon Hesterlee. Boy, if only we had a Sharon Hesterlee.

Sundays are not my favorite days. People rest. I fidget. On Sunday some months ago, I received a message from Sharon Hesterlee. She wanted to talk. The thing is, I like to talk with Sharon Hesterlee. I met her long ago, when she joined the MDA to lead their research investments. She is smart, well-versed, knows the field and the players. She understands the investments and is a well-respected leader in the field. She knows the obstacles, the bottlenecks, and the politics. And, she has been around this community for over 10 years. She understands the value of developing collaborations, recognizes the need to leverage money, and understands all of the moving parts. This Sunday was looking up!

I called. We discussed a range of issues, most specifically her interest in focusing on a single disease – Duchenne. You might imagine, I was smiling. And thrilled when she said she would like to work for PPMD. I called John Killian (our Chairman) and he connected with the Board. Sharon flew into NJ and met the staff. Sometimes you just know things and this felt exactly right.

After trying my best not to shout this news from the rooftops for the last few months, I’m thrilled to be able to say – Sharon Hesterlee works for PPMD. She is Senior Director of Research and Advocacy.

Some days, the stars line up just right. Happy 2010.

Holly PA

What’s new at PPMD? Holly Peay (pronounced P-A). Well, not exactly new, but new in that Holly has joined the staff of PPMD! We first met Holly when working on DuchenneConnect, the patient self-report registry. She came highly recommended as a genetic counselor, an educator, and an all-around, really smart woman. Her task was to create educational materials for families and for providers – educational information about Duchenne, about genetic testing, about care, about research, about clinical trials; and present it in such as way, that it would be comprehensive and understandable, even if the information was really fresh and even if tears might get in the way of your reading from time to time. She did it! She made very difficult information understandable.

Through DuchenneConnect and the PPMD Community site, we heard stories. Stories about delays in diagnosis…months…years at times. We thought about what we might do to help. We had some experience.

We submitted a grant to the Center for Disease Control (CDC) and were granted a cooperative agreement. The goal of the grant is to educate, to raise awareness about muscle weakness, and to impact the diagnostic odyssey. Our initial experience was in Mississippi. We developed partnerships with healthcare professionals likely to see children in the early years of life (ages birth to 5 years). We wanted to understand what happens when mom, dad, gram, or anyone really, expressed concern about a child’s muscle strength. What words did they use? What happened when they raised concern with the doctor (nurse, physician’s assistant, healthcare professional, teacher).

And we learned that some of the time, concerns are dismissed. We learned that some doctors/healthcare professionals are not exactly sure what they are to look for. We learned that some of the time, referrals to specialists are difficult with long waiting times. We learned that sometimes the response is to send the child to a PT or put them into an exercise program to improve strength. And the diagnostic odyssey continues. Typically mom, dad, gram’s worry is relieved for only a short time because they see something is still not quite right.

With this current cooperative agreement, we are expanding our horizons. Our goal is to educate healthcare professionals and this time, not in just a specific state but rather now through the professional societies. There are too many acronyms to list – but professional societies of every healthcare professional group you can think about – pediatrics, family doctors, physician’s assistants, nurse practitioners, nurses, physical therapy…you get the gist.

We have expanded this effort to include ‘primary muscle disorders of childhood’ – because the message will have greater impact. And Duchenne is the most common

We have developed common messages:

• Watch them walk, run, climb (in the confines of an exam room, sometimes it is difficult to really see what mom, dad, gram is talking about)
• Developmental Delay, include a CK (you already know this one)
• YOU CAN ALWAYS DO SOMETHING! (this is for everyone –do not dismiss worries/concerns. Typically when someone loves someone, they are pretty observant and usually right.)

There is a Task Force leading this effort. Kathy Matthews, MD is Chair. Brian Denger is Project Manager. Task Force Members include representatives from Professional Societies and Advocacy organizations - MDA, PPMD, CMD, SMA.

Holly Peay is the PI on this grant. She is now part of us, part of PPMD. If you see her in the hall, please say hello.