CureDuchenne - Together we Can CureDuchenne
September 2012

Scientist of the Month - Eric Hoffman

Eric Hoffman
Eric Hoffman, Ph.D

This month we have a featured Q&A with Eric Hoffman, Ph.D, director, Research Center for Genetic Medicine, George Washington School of Medicine and Health Sciences, Children’s National Medical Center, Washington DC. Dr. Hoffman shares his insights on where we are with Duchenne research.

Q: Tell us about the projects you are currently working on.
A: We have about 50 clinicians, scientists, and clinical trialists working specifically on DMD, covering many topics from what dystrophin normally does in muscle and what goes wrong when it is missing (basic science), developing new approaches to therapy (translational research), and bringing potential therapies to clinical trials (clinical research). We have also spun off a drug development company focused on DMD (ReveraGen Biopharma), and work with Sarepta on development of exon skipping (pharmaceutical projects).

Our two major pharmaceutical projects are on VBP15 and exon skipping. VBP15 (ReveraGen Biopharma) appears to have a number of activities that appear beneficial to dystrophin-deficient muscle. It is an inhibitor of NFkB (a key inflammatory pathway in dystrophic muscle), and helps stabilize dystrophin-deficient muscle plasma membranes. Pre-clinical studies in mouse models have shown impressive results, and we expect to be in human trials in 2013. With regards to exon skipping we work closely with Sarepta on a number of projects. We lead Department of Defense supported projects that enabled the IND for the current exon 51 phase 2 trial (Jerry Mendell), and are similarly working on bringing eon 45 drug to trial. We run two large NIH-supported projects on exon skipping one optimizing dose schedules, and a second looking at predicting the clinical response to different skipped (Becker-like) dystrophin proteins. The latter includes the first large natural history study of Becker muscular dystrophy through our CINRG clinical trial network ( CureDuchenne helps support these pharmaceutical interactions via support of Abby Bronson (previously of MedImmune) in our shop (together with Foundation to Eradicate Duchenne).

Our clinical and translational research projects include pre-clinical trials via a large DMD mouse drug testing facility (run by Kanneboyina Nagaraju) (about 40 trials done to date), and the Cooperative International Neuromuscular Research Group (CINRG) clinical trial network. The CINRG group is working on clinical and biomarker outcome measures for clinical trials in DMD, trains a network of clinical evaluators for trials, and assists pharmaceutical companies with designing and running their trials in DMD. I serve as Scientific Director of CINRG, Paula Clemens at Pittsburgh is the Medical Director, and Avital Cnaan in our shop runs the statistical and coordinating center for CINRG.

Q: What are the goals and objectives of your research?
A: To make DMD a much less severe disease. I made a commitment to myself to do this many years ago, otherwise I’m not allowed to retire.

Q: Where are we currently with research related to exon skipping?
A: All the animal studies done with the morpholino chemistry suggested that this approach should work well in DMD patients, including our trials in DMD dogs with Shin’ichi Takeda’s group in Tokyo. The data from both Francesco Muntoni’s and Jerry Mendell’s trials are what we would expect to find, and all this is extremely encouraging. We need more trials with more exon skipping drugs in more DMD patients, and all this is expensive, but these are ‘good shots on the goal’.

Q: What are you excited about in terms of Duchenne research?
A: I’ve been in DMD research a long time (since 1986), where I worked with Louis Kunkel as a post-doc to help identify the DMD gene and identify dystrophin. Once the gene and protein were identified, many folks said, “We know what causes DMD; we’re done!” At the time, I felt, “Whoa, what about the DMD patients?!” The next 15 years was tough; funding was thin, and research seemed to be more similar to betting on horse racing than a ‘broad healthy portfolio’. The last 10 years has seen a tremendous turn to a bright new future lots of really good approaches by a lot of different groups internationally, with some impressive support from many governments and foundations. The coordination and cooperation between groups is also impressive now (like it was in the 1980’s). I guess I’m excited about everything Duchenne now!

Q: What is your hope?
A: That soon we’ll just remember what DMD used to be like.

Q: What are the next steps?
A: INDs, trials, INDs, trials, repeat!

Q: How did CureDuchenne support help you?
A: Academic/industry interactions that are smooth and ‘trans-culturally correct’ are critical to move DMD therapeutics forward. CureDuchenne recognized this early on, and has helped support Abby Bronson at Children’s National Medical Center to facilitate our interactions with industry. CureDuchenne also provided a critical loan to ReveraGen as it was getting started. This helped us leverage significant support from both NIH TRND program, and MDA Venture Philanthropy. Children’s National Medical Center led a collaboration with CureDuchenne and the Foundation to Eradicate Duchenne to fund preclinical work for Sarepta (formerly AVI BioPharma) to proceed to human clinical trials.

Q: What role does CureDuchenne play in drug development and discovery?
A: CureDuchenne has been forward thinking in fostering industry involvement with DMD, such as the impressive Prosensa/GSK exon skipping initiatives.

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