Groundbreaking Research on Gene Editing for Duchenne Presented at ASGCT

The 2017 American Society of Gene & Cell Therapy took place in Washington DC last week. The Duchenne community was treated to a wealth of data from projects utilizing gene editing and gene therapy to treat Duchenne muscular dystrophy. On Wednesday, May 10, the well-attended session entitled “Gene Therapies for Musculoskeletal Diseases was chaired by Dr. Carsten Bonnemann, MD and Dr. Jerry R. Mendell, MD. The session featured robust work from many academic labs in the Duchenne space including:

Niclas Bengtsson, PhD (University of Washington): In an oral abstract entitled “Systemic Gene Editing for Muscular Dystrophy Using AAV-CRISPR/Cas9”, Dr. Bengtsson presented data demonstrating an ability to use SpCas9 and SaCas9 delivered via AAV6 to correct mutations in Duchenne.

Jacqueline Robinson-Hamm, PhD (Duke): In an oral abstract entitled “Dystrophin Restoration in a Humanized Mouse Model of Duchenne Muscular Dystrophy by Gene Editing with S. aureus Cas9”, Dr. Robinson-Hamm showed that an approach using SaCas9 and two guide-strands encapsulated in separate AAV9 vectors could be used to correct mutations in Duchenne. Given the smaller size of SaCas9, Dr. Robinson-Hamm expressed optimism that her next effort might succeed in combining both SaCas9 and two guide-strands in a single viral vector.

Rika Maruyama, PhD (Alberta): In an oral abstract entitled “Systemic Injections of Peptide-Conjugated Morpholinos Improve Cardiac Symptoms of a Dog Model of Duchenne Muscular Dystrophy”, Dr. Maruyama in partnership with Sarepta demonstrated feasibility of next-generation PMO technology to treat Duchenne in a canine model.

Nicolas Wein, PhD (Nationwide): In an abstract entitled “Prolonged Exon 2 Skipping and Robust Dystrophin Expression 1 Year Post Single Neonatal Injection of an AAV9.U7snRNA Vector in the Dup2 Mouse”, Dr. Wein demonstrated that a U7 guide strand packaged in AAV9 could be used to treat rare Duplication 2 mutations in a mouse model of Duchenne. In partnership with the patient community and Dr. Kevin Flannigan, CureDuchenne has been a long-time sponsor of this work which we hope to help translate into a clinical trial at Nationwide Children’s hospital this year.

Perhaps the highlight of the conference took place during the George Stamatoyannopoulos Lecture on Thursday May 11. Dr. Eric Olson, PhD, Chair of Molecular Biology at UT Southwestern, was honored to give a presentation demonstrating how his research on gene editing technologies like CRISPR/Cas9 and Cpf-1 can be used to correct mutations that lead to Duchenne muscular dystrophy. Dr. Olson’s presentation highlighted the importance and therapeutic value of advancing work in gene editing therapies for Duchenne, and showed how a single-guide strand and SpCas9 delivered by AAV9 could potentially be used to treat Duchenne patients with point mutations, deletions, duplications, and pseudo-exons. Dr. Olson reported that the ground-breaking work in his lab has been able to achieve 80-90% restoration of dystrophin production in a mouse model with deletion of exon 50 that without therapeutic intervention makes less than 1% dystrophin.

Dr. Olson is excited to continue translation of his exciting pre-clinical research in Duchenne into a clinical therapy through a biotech company he has collaborated with CureDuchenne to form called Exonics Therapeutics. CureDuchenne is actively looking for partners in the patient community that would like to join in funding support for Exonics, to translate Dr. Olson’s transformational CRISPR/Cas9 research, into a potential therapy to treat Duchenne patients in clinical trials.