As always I want to extend a very big thank you to all the researchers that are working on therapies for Duchenne. There are a plethora of interesting disease for them to work on, most of them having a much larger patient population. I know I speak for all families of boys afflicted with DMD in expressing my appreciation for their dedication.
The New Directions in Biology conference is a very technical meeting that concentrates quite heavily on basic cell biology, including signaling systems, immune reactions and the multitude of proteins that are involved in muscle cells. Here are just a few of the highlights that pertain to potential treatments for DMD:
Gene Therapy: Dr. Jeff Chamberlain presented his work on AAV6 using a hinge 3 micro-dystrophin. His mdx experiments show good delivery into the heat, medium delivery into diaphram muscles and less efficient delivery into skeletal muscle when delivered via the jugular. Limb profusion will be the method used to deliver to legs once his pre-clinical and proof-of-principal stages are complete. Dr. Xaio Xaio presented the results of the gene therapy trial conducted by Asklepios. They did not see any dystrophin present, however, they did not use immunosuppressant in this trial. They did find what they believe is a reaction to dystrophin, obviously not what any of us want to hear. There are many ways to look at this and it does warrant research into this issue. Here’s an article by Annemeike Aartsma-Rus from the TREAT-NMD website that discusses this and other therapies: http://www.treat-nmd.eu/patients/DMD/anti_dystrophin_immune_response/
Dr. Kathryn Wagner presented data on myostatin inhibition and showed data using Acceleron’s compound. There is hope that myostatin inhibition can increase muscle mass and also decrease fibrosis. Preliminary data from Acceleron also show an increase in bone density in mdxmice treated with their compound, ACE-031. Accleron has begun their phase ll trial in DMD boys in Canada.
Dr. Beth Barton gave a presentation on GRP94 and it’s affect on IGF-1. Local production of IGF-1 in muscle is important and GRP94 may be a new therapeutic target to boost IGF-1
Dr. Kevin Campbell and Justin Percival both discussed nNOS as a regulator of skeletal muscle performance. It’s too soon to know if it will increase muscle strength and decrease fatigue. Sildenafil (Viagra) will hopefuly enter clinical trials soon to evaluate it’s benefit for DMD cardiac. This trial will be led by Charley’s Fund and co-funded by CureDuchenne.
Dr. Lee Sweeney gave an update on Ataluren and showed data to support continued investigation into the drug administered at lower doses to hopefully obtain results. Data analysis is still on-going.
There were many more very informative presentations and the attendees were treated to a wonderful dinner at the Canadian Musuem of Civilization.
Somehow the "research" on mice, dogs and multi-flavored acronyms doesn't have the same 'WOW" factor as it did for me when our son was diagnosed 12 years ago. But, hey it always looks good on a resume...