mRNA Vaccine Technology Treats Rare Disease Patients

Massachusetts-based Moderna, Inc., announced today the first patient has been dosed in the Phase 1/2 study evaluating the safety and tolerability of mRNA-3705, its investigational mRNA therapeutic for methylmalonic acidemia (MMA), administered via intravenous infusion in patients with isolated MMA due to MUT deficiency.

Methylmalonic acidemia is a rare, life-threatening, inherited metabolic disorder that is most commonly (approximately 60% of cases) caused by a deficiency in the mitochondrial enzyme methylmalonic-CoA mutase (MUT), says the U.S. NIH.

This deficiency can lead to metabolic crises due to a toxic buildup of acids in the body and progresses into multi-organ disease.

As a result, MMA is associated with significant mortality and morbidity, and there are no approved therapies. Standard of care includes dietary and palliative measures.

Currently, liver or combined liver and kidney transplant is the only effective treatment.

mRNA-3705 is designed to instruct the body to restore the missing or dysfunctional proteins that cause MMA and consists of mRNA encoding human MUT, the mitochondrial enzyme commonly deficient in MMA, encapsulated within Moderna’s proprietary lipid nanoparticle (LNP).

mRNA-3705 has been granted Orphan Drug and Rare Pediatric Disease designation by the U.S. FDA.

“We are delighted to have been able to treat the first patient in the world with this new medicine here in Birmingham,” stated Saikat Santra, M.D., Pediatric Inherited Metabolic Medicine Consultant, Clinical Inherited Metabolic Disorders at Birmingham Women’s and Children’s NHS Foundation Trust, in a press statement issued on August 16, 2021.

“We sincerely hope that it brings this brave patient, and many more like them, a brighter future free of the restrictions of this terrible disease.”

In addition to MMA, Moderna is working to advance mRNA therapeutics that restore the activity of missing enzymes responsible for other rare diseases, such as propionic acidemia (PA), glycogen storage disease type 1a (GSD1a), and phenylketonuria (PKU). 

Located in Cambridge, MA, Moderna has active clinic programs in five different therapeutic areas: infectious disease, oncology, cardiovascular, rare disease, and autoimmune disease.