Australian biotechnology company, Benitec Biopharma, recently published pre-clinical results for its oculopharyngeal muscular dystrophy (OPMD) gene therapy programme in the scientific journal, Nature Communications.
This research represents a collaboration between Benitec, Professor George Dickson at Royal Holloway University of London (RHUL) and Dr Capucine Trollet at the Institute of Myology, Paris. Muscular Dystrophy UK was not involved but currently supports Professor Dickson through several gene therapy projects including UNITE-DMD.
OPMD is caused by a mutation in the PABPN1 gene, which causes mutant PABPN1 protein to accumulate and form clumps inside the nuclei of muscle cells. These clumps are thought to disrupt cell functioning, leading to muscle cell death.
Benitec has developed a unique technology called DNA-directed RNA interference (ddRNAi), which can silence (switch off) a particular gene. In this study, the company designed a ddRNAi strategy to silence the mutated PABPN1 gene in a mouse model of OPMD. The ddRNAi was packaged into an adeno-associated virus (AAV), which also contained a new, healthy copy of the PABPN1 gene. The AAV was then injected into the muscles of the mouse models.
The combination of the ddRNAi and the healthy PABPN1 gene effectively ‘silenced and replaced’ the mutant PABPN1 gene. This significantly reduced the amount of mutant PABPN1 clumps in the mouse muscle. It also reduced muscle scarring (fibrosis) and improved muscle strength.
Benitec received Orphan Drug Designation for its OPMD gene therapy programme earlier this year. This is a special status granted by the European Medicines Agency (EMA), which can help to speed up the development of therapies for rare diseases.
Benitec and its collaborators are currently developing a next-generation OPMD gene therapy to take forward into clinical trials. They hope to initiate a phase I/II study in OPMD patients in 2018.
Professor George Dickson, who led the research based at RHUL, said:
This is an important and exciting advance. Our data provide a critical proof that gene therapy may be able to treat this orphan disease, and highlights the unique aspect of Benitec’s technology to achieve silencing of aberrant genes and their replacement with healthy copies. With European Orphan Drug Designation already approved, we look forward now to streamlining the process towards clinical trials. Our successful MDUK research developing AAV-mediated gene therapy for Duchenne muscular dystrophy has provided technological expertise that enabled this program to move ahead with maximum efficiency.
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