A single injection of a promising double gene therapy in a OPMD mouse model

Oculopharyngeal muscular dystrophy (or OPMD) is a relatively rare type of muscular dystrophy that tends to affect and older population. This condition is transmitted in an autosomal dominant manner, and results in the gradual development, from 50 years of age, of the bilateral drooping of the eyelids and difficulty swallowing, and also the appearance of pelvic girdle muscle deficiency. Symptom progression is slow, but often results in marked dysphagia with a high risk of aspiration pneumonia and malnutrition. The presence of nucleotide triplet expansion in the PABPN1 gene is responsible for this disease. This gives rise to the production of polyalanine residues that are toxic to the cells.


In an article published in February 2021, a Franco-American team published promising results for a gene therapy that administers, in a single intramuscular injection, a double sequence that “switches off and replaces” the mutated PABPN1 gene. This product, BB-301, administered to mice models of OPMD, restored muscle weight and strength.

The same team had provided proof of concept for a double gene therapy (one that switches off, the other that replaces) for OPMD in 2017.

In a press release, Benitec Biopharma, the company developing BB-301, announced the conduct of encouraging preclinical studies in anticipation of a clinical trial in humans that could begin in 2022.

BB-301 obtained orphan medicinal product designation in Europe and the United States.


BB-301: a silence and replace AAV-based vector for the treatment of oculopharyngeal muscular dystrophy. Vanessa Strings-Ufombah, Alberto Malerba, Shih-Chu Kao, Sonal Harbaran, Fanny Roth, Ornella Cappellari, Ngoc Lu-Nguyen, Keiko Takahashi, Sophie Mukadam, Georgina Kilfoil, Claudia Kloth, Petrus Roelvink, George Dickson, Capucine Trollet, David Suhy. Mol Ther Nucleic Acids. 2021 Feb 18;24:67-78.


Benitec Biopharma Inc., Press release (2021-02-24): Benitec Biopharma Announces Successful Results from the Interim Analysis of the BB-301 Pilot Dosing Study