Posted on 03/04/2017
Key pre-clinical data on oculopharyngeal muscular dystrophy (OPMD) published in Nature Communications
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disorder characterised by eyelid drooping (ptosis), swallowing difficulties (dysphagia), and proximal limb weakness and can be life-threatening. A rare inherited myopathy, OPMD is caused by an abnormal expansion of a GCG triplet repeat in a gene encoding PABPN1 protein. Once abnormal, PABPN1 forms aggregates in nuclei of OPMD patients and currently there is no cure.
New collaborative work initiated by Professor George Dickson and researchers at the School of Biological Sciences, Royal Holloway, University of London, the Institut de Myology (Paris) and an Australian biotechnology company Benitec BioPharma has demonstrated the effectiveness of an innovative gene therapy for OPMD.
The combination of two gene therapy vectors termed AAVs (adenoassociated virus vectors), one allowing the inhibition of mutated PABPN1 by RNA interference, and the other bringing a functional PABPN1, significantly reduced the amount of aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalises the expression of RNA. The efficacy of the combined treatment was also confirmed in cells derived from OPMD patients. These results, whose objectives were to establish a proof of concept, were published on 31 March 2017 in Nature Communications and pave the way towards a gene replacement approach to OPMD treatment.
“This is an important and exciting advance,” said Professor Dickson. “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 health copies. With European Orphan Drug Designation already approved, we look forward now to streamlining the process towards clinical trials.”
Nature Communications, an open access scientific journal is published by the Nature Publishing Group. The research paper can be read in full at this link
Professor George Dickson and his research team received a national award for its world-class research in the development of novel therapies for rare diseases, such as Duchenne Muscular Dystrophy (DMD) in 2014. Find out more about Professor George Dickson and his research at Royal Holloway.
OPMD is a rare inherited myopathy characterised by dysphagia (difficulty in swallowing), the loss of muscle strength, and weakness in multiple parts of the body. Patients typically suffer from severe dysphagia, ptosis (eye lid drooping), tongue atrophy, proximal lower limb weakness, dysphonia (altered and weak voice), limitation in looking upward, as well as facial muscle and proximal upper limb weakness. Progressing throughout that patient’s life, OPMD is not typically diagnosed until the individuals reach their 50’s or 60’s. As the dysphagia becomes more severe, patients become malnourished, lose significant weight, become dehydrated and suffer from repeated incidents of aspiration pneumonia. These last two are often the cause of death. No cure is currently available for OPMD. The cricopharyngeal myotomy is the only treatment available to improve swallowing in these patients, but because the root cause of the genetic disease has not been addressed, the pharyngeal musculature still undergoes progressive degradation leading to the aforementioned complications.