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January 22, 2008
Treat-NMD
I hope you have heard this term or read the newsletters posted on our site, but I realize you may still be wondering just what it means, how it works, and what is supposed to happen. As we start this new year, it will be important to understand. Since I am a member of the STAC – the Scientific and Technology Advisory Committee for Treat NMD, I thought I might try to explain.
First off Treat-NMD is primarily supported by the European Union, better known as the EU. It is a broad collaborative program designed to advance treatments and cures for neuromuscular disorders. They are first concentrating on Duchenne and SMA because there is a general belief and sufficient scientific evidence to suggest that promising treatments are on the horizon.
Treat-NMD is a developing clinical trial network within Europe. We are working to parallel this effort in the US with the goal of a global network. You might be thinking, why all this when treatments are on the horizon? Why can’t we simply organize a few sites for clinical trials, test the strategy, hope it works – prove that whatever we are trying has benefit (which is no simple matter by the way), get the therapy approved, and close the door on Duchenne? I wish it was that simple.
Consider Treat-NMD as an assembly line in a factory and this ‘factory’ has all the machinery to evaluate a certain strategy, move it through the required machinery, and once the process is complete, the ability to conduct clinical trials. This assembly line, while not very sexy, is essential to facilitate and accelerate treatments for Duchenne.
What are the components of Treat-NMD, this new ‘factory’ for Duchenne?
1. TNCC – This is the Treat-NMD coordinating Center. This is the nuts and bolts or administration of the system. TNCC will be the virtual manager of Treat-NMD and work to insure sufficient money is pumped into the system to continue momentum.
2. Centers of Excellence – These are individual machines, core centers where extensive expertise exists in research and clinical care (think Wellstone Centers in the US). To date, in Europe there are 85 participating centers.
3. Shared Resources – These are raw materials. This refers to animal models, genetic/genome analysis, facilities, protein analysis, culture facilities stem cell biology facilities, bioinformatics, and patient databases. (Wellstone centers in the US utilize shared resources)
4. Production, Toxicology, Safety, and Delivery of Therapeutics (product safety) – This group will standardize procedures for production, GLP bio-distribution, and safety of therapeutic agents. They are currently concentrating on AON and viral vectors.
5. Clinical Trials Coordination Center (quality assurance) – This center will design and implement infrastructure to conduct comparable clinical trials. This group interacts with regulatory agencies in order to overcome regulatory hurdles and has easy access to all those centers with the capability to perform clinical trials. Keep in mind, not all Centers of Excellence will be able to perform clinical trials. Some of the Centers of Excellence will focus on research. (The same is true for the US Wellstone Centers)
a. Outcome Measures. This is a tough one. How to determine or prove benefit. They will evaluate current outcome measures and work to identify and validate primary and secondary outcome measures in DUCHENNE. This will include reviewing methods for evaluating and measuring the upper body to insure participation of both ambulatory and non-ambulatory boys
b. Standards of Care. Developing best practice guidelines and implementing those guidelines across sites. Treat-NMD is working with CDC to facilitate these ‘standards’ or guidelines internationally. This is fundamental to identifying/measuring benefit.
6. Extension of the network to include Industry, patient organizations, researchers, and clinicians with the goal of implementing cutting edge therapeutics developments. This is the outreach to consumers (patients) and clients (industry)
7. Human Resources – Maintenance
a. Training staff – educating researchers and healthcare professionals to insure consistency and quality.
8. Advertising – spreading the word to physicians, industry, and patients in order to: identify patients, make early and accurate diagnosis, and provide access to genetic testing, standards of care, and treatments.
9. Ethics – Ensuring Truth in Advertising. Exploring stakeholders concern, ensuring all patients have access to treatment, are treated equally, and are able to participate in clinical trials..
Putting the pieces together in a systematic way is essential. Treat-NMD exists to eliminate fragmentation in the neuromuscular field by harmonizing research efforts across the community from basic research to the development of new and cutting edge therapies and treatments for our sons. In the US, thanks to our champions in Congress and your advocacy, we are working to mirror Treat-NMD, thus connecting to this global network. In order to demonstrate something works to the regulatory agencies, we will need a significant number of boys to participate. The upcoming PTC 124 trial will involve 165 boys at 26 different sites. This is no small task, but at the end of the day, we have our fingers crossed and pray that PTC 124 becomes the first treatment for a subset of boys and that this trial builds the expressway to facilitate other promising trials.
Posted by ppmd at 11:04 AM | Comments (0)
January 16, 2008
The Race
For the last 4 years, I have been inspired by the Disney Marathon. I watched, I cheered, and my eyes filled with tears as I our runners ran by. These marathons are magic for me, all of them, but especially the Disney marathons. While in Disney, you will hear the words “have a magical day†from every member of the Disney cast. For the last 24 years, I have been wishing for magic for Duchenne, and maybe early on believing I could find a magic wand for my boys…and that it would be in time. On these few days we spend in Disney, there is a magical quality about our lives and our loves, where time stands still and we are in tune with each other.
This year I ran the ½ marathon at Disney . You know how you have a certain thought in your head and the next thing you know, you say something out loud, that at that very moment makes sense? Then, just as soon as those words escape your mouth, you want to catch them and take them back? Those words “I’ll run next year†escaped from my mouth just after the celebration dinner at the 2007 marathon. I was not drinking, but I do admit to some euphoria at this celebration of our families. Endorphins probably, but I wondered if those same endorphins would show up as I crossed the start line and sustain me until the end. Ok, Ok, I realize millions of people run marathons. I was not so different, but then again, I did have significant reason to doubt. At 61, I had never run a marathon. Hell, I had never run a mile. I do walk and I hoped this might be one thing in my favor.
I worked out the details in my head. I decided to start training a minimum of 4 days a week. It was Spring 2007. I had a lot of time to prepare. The moment dinner was over, I headed out, iPod loaded and Tina Turner singing in my ear. I ran for the first five minutes, quickly running out of steam, and power walked for the next hour or so, walking approximately four miles a night. Four miles is a far cry from 13.1 and I quickly realized I would have to run more, walk faster, and cover more than four miles. Fall came and with it, my travel increased. In my head I made plans to use the hotel treadmills to continue my training. I did occasionally, but I had any number of excuses why the treadmill idea did not fly. Fundamentally, I find the treadmill boring and the concept of walking and going nowhere seems somehow unacceptable.
The Disney marathon is the first weekend in January following the holidays. January 12, 2008 was the ½ marathon and the date resonated in my head like a broken record (or a scratched cd). During Thanksgiving, I increased my training, walking five to six miles maybe three days a week. I was strength training, taking Pilates, and run/walking five to six miles. It did not seem sufficient to complete a 13.1 mile run. Each time I drove somewhere, I tracked mileage. How far was 13.1 really? Pretty damn far I realized.
I argued the commitment in my head. I developed a long list of excuses why I would not run to include:
o Too dark after work
o Travel
o Caring for the Goldens ( 91-year old mother and 95-year old mother-in-law live with me)
o Holidays
o Needed to be part of the cheering section
o Too old to start
o Lack of training
o Lack of endurance
o Threat of the Disney bus picking me up
o Failure
On the other hand I had a list of reasons why I wanted to run:
o For my sons and daughters
o A commitment to take all the steps Chris and Patrick were denied
o Because many people agreed to support my run
o To live up to expectations
o Because many people believed in me and were cheering for me
o To encourage novices like myself to try
o To suggest that it is never too late to participate
o To suggest that participation matters
o To convince myself that I had it in me
o To start something new
The day before the race I called Tom Neupauer, discussing my lack of training, hoping he would say I should not run. He thought I could make it if I would conserve energy and stay consistent. Just before the race I told Kimberly, I was unsure. I woke that morning at 3 AM and the excuses why I should not run were flashing in my head like a neon sign. I started coughing and decided I was getting the flu, and should not run. I left the room, found Ryan, and got on the bus. There was no turning back. I was caught in the excitement, the sense that we were all in this together. I felt the energy of the 22,000 people. The excitement was palpable. Thank God for endorphins!!
The stories about why people run in this event, the promise to an organization or individual, the commitment to help, were shared while we waited in corrals to start. John Killian, Ryan Fischer, and I became a team. I was the weak link, but they tracked the time, often reminding me of the need to increase my speed. They also periodically threatened me with the Disney bus! The hours and miles passed quickly. Mile 11, Mile 12 and suddenly the end was in sight. Success! I became a runner, ok a walker, but someone who can and did complete a ½ marathon.
Claudia Hirawatt was right about the marathon. She said it was better and more fun than her wedding. My training (ok, so it could have been better) and completing the marathon inspired me and convinced me that we are powerful when we work together and we are and will continue to work toward our goal: to EnDuchenne.
Posted by ppmd at 09:29 PM | Comments (0)
January 03, 2008
A Bedtime Story For 2008
I find there’s always a story behind the story and antisense oligonucleotides, or exon skipping, has a wonderful story. PPMD started in April, 1994. In December 1994, Elizabeth Vroom started Duchenne Parent Project (DPP), in the Netherlands. Elizabeth is a Duchenne mother from Amsterdam. Our first steps together were to develop the Duchenne Muscular Dystrophy Research Center (DMDRC) at the University of Pittsburgh. You now know this as CINRG.
Elizabeth held the first European Duchenne conference in Rotterdam in 1997. Eric Hoffman was one of the speakers and while in Rotterdam he visited the University of Leiden and met a young PhD, Judith VanDeutekom. Elizabeth agreed to provide fellowship support for Judith to work with the group at the DMDRC. Judith spent a year in Pittsburgh and following, returned to Leiden to continue her work.
In 1998 DPP and advisors reviewed Judith’s proposal on antisense oligonucleotides or exon skipping. The proposal reviewed well. This strategy was not new, but rather was under investigation in a number of other areas, just not DMD. The advisors were positive about the work and DPP provided support. This support continued for the next 9 years. Exon skipping worked in the mdx mouse. Judith developed a mouse with human DNA to further investigate the approach. She was positive about the approach. We were all thrilled, though we knew it would take time to translate.
DPP continued to underpin this work. As Judith thought about moving from bench research into the clinic, she recognized the need to partner with Industry. The Dutch company Prosensa and Judith seemed a good fit. DPP was already onboard and expanded their support to include Prosensa. Elizabeth reached out to her sister organizations –Germany (Aktion Benny & Co), Italy (DPP), USA (PPMD), and Monaco – and expanded support for the project.
The DPP investment in development and translation of exon 51 is more than $4 million. Without Elizabeth and DPP, exon 51 skip and this technology may still be in the lab. The New England Journal article confirmed proof of concept in man. The New York Times, on December 27, suggested exon skipping has the potential to become a treatment for a subset of boys with DMD.
Parents can indeed change the world. We are willing to invest in solid research, think outside the box, and stay the course. It is all about building together and buying a lifetime.
Happy New Year!
Posted by ppmd at 02:00 PM | Comments (0)