HOPE FOR JAVIER’S SOLE FOCUS IS TO IDENTIFY & ADVANCE PROJECTS THAT HAVE THE BEST CHANCE AT PROLONGING LIFE EXPECTANCY IN DUCHENNE.
EVERYTHING WE DO MUST HAVE A ‘YES’ IN ANSWER TO “WILL THIS HELP ADD YEARS TO THE LIVES OF BOYS WITH DUCHENNE?”
DUAL AAV MINI-DYSTROPHIN GENE THERAPY IN DYSTROPHIC DOGS
A team, led by Dr. Dongsheng Duan, at the University of Missouri, developed a microgene; a miniature version of the dystrophin gene. In testing, this minimized dystrophin gene protected all the muscles in mice with DMD. Dogs have a body size similar to that of an affected boy, and they develop DMD in a naturally similar manner as humans. Over the next ten+ years, the team developed a strategy to advance from mice to dogs and safely send the micro-dystrophin gene to every muscle in dogs afflicted with the disease. The dogs receiving treatments continued to develop normally.
Hope for Javier provided funding when it was needed most, to bridge a gap, while the researchers were waiting for larger grants from government agencies. The funding we provided shaved years off a project that has the potential to add years to boys’ lives.
Dr. Duan recently received a five-year, $3 million grant from the NIH to continue his research.
You can learn more about this exciting work here: University of Missouri News Bureau
Or in this Oxford Journal publication: Oxford Journal – Human Molecular Genetics
CRISPR/Cas9 Genome Editing
The CRISPR/Cas9 genome-editing platform is a promising technology that corrects the genetic basis of hereditary diseases. The versatility, efficiency and multiplexing capabilities of the CRISPR/Cas9 system enable gene correction strategies.
CRISPR/Cas9-editing aims to eliminate the mutation itself. It is a single therapy that could, in theory, provide a permanent cure.
Dr. Dongsheng Duan and his team at the University of Missouri demonstrated, for the first time, effective gene editing and muscle function enhancement, in adult mice bred with Duchenne. Since the Cas9 gene is derived from bacteria (Staphylococcus aureus), it is expected to cause strong immune responses in mammalian tissues and is likely to result in immune rejection. To truly take advantage of the tremendous potential of the CRISPR/Cas9 technology for DMD gene therapy, we have to overcome the immune response to Cas9. For the project we are funding, the team will design a low immunogenic AAV Cas9 vector to be tested in mice.
You can learn more about the CRISPR gene-editing technology in a NY Times article here: NY Times – CRISPR
HT-100: A Powerful Anti-Inflammatory and Anti-Fibrotic
HT-100 (also known as “Halo”) is an anti-fibrotic medication that we hope will prevent and maybe even reduce fibrosis. When boys do not make dystrophin, a cascade of negative events occurs in their muscles. Fibrosis, or scar tissue, is a key factor in the domino effect. Scientists have known about halofuginone for a long time but this medicine didn’t make it very far in previous clinical trials for other diseases. One reason is that the drug caused severe nausea and vomiting. HT-100 is a new formulation of halofuginone that involves a special coating designed to enable the drug to bypass the stomach.
In June of 2015, Halo showed positive interim clinical data with statistically significant improvements in muscle strength from an ongoing Phase 1b/2a clinical program with HT‐100. Read more about this exciting news here: Akashi HT-100 Clinical Update