20 December 2017 - - Cambridge, Massachusetts-based messenger RNA therapeutics (mRNA) and vaccines developer Moderna Therapeutics has published preclinical data supporting its first rare liver disease development program, an mRNA therapeutic for methylmalonic acidemia (MMA), the company said.
The data, published online in the journal Cell Reports, demonstrate that intravenous administration of an mRNA therapeutic encoding for human methylmalonyl-CoA mutase, the enzyme most frequently mutated in MMA, enabled liver expression of MUT in MMA mouse models, leading to a significant reduction in methylmalonic acid, a substantial improvement in weight gain, and the complete survival of the full cohort of treated mice versus control group.
Repeat IV dosing did not increase markers of liver toxicity or inflammation.
The study was conducted in partnership with researchers in the Medical Genomics and Metabolic Genetics Branch of the National Human Genome Research Institute at the National Institutes of Health. Both Moderna and NIH researchers conducted research for the study.
MMA, is a rare, autosomal recessive organic acidemia/aciduria, most commonly caused by a deficiency of the enzyme methylmalonic CoA mutase, due to a defective or missing MUT protein. It is primarily a pediatric disease with onset in early infancy and associated with significant mortality and morbidity. Currently, liver and/or kidney transplant is the only effective treatment.
Moderna is developing an mRNA therapeutic, mRNA-3704, which directs cells in the liver to produce and express a functional MUT enzyme, restoring the metabolic pathway and reducing toxic acid build-up.
Privately held Moderna is developing mRNA vaccines and therapeutics as a new class of medicines for infectious diseases, cancer (immuno-oncology), rare liver diseases, cardiovascular and pulmonary diseases, through proprietary development and collaborations with strategic partners.