Methylmalonic acidemia (MMA) is a rare disease affecting the metabolic system. 60% of all cases are due to a deficiency in MUT, a mitochondrial enzyme, which causes acids to buildup in the body.
Sadly, there has yet to be an approved treatment for this disease. The standard of care aims to relieve pain. A special diet may also be prescribed. Additionally, patients may require a liver transplant or kidney transplant.
However, Moderna has just announced that they have enrolled the first patient in a new Phase 1/2 study investigating a potential therapeutic option for this condition.
Phase 1/2 Study
This study will evaluate both the safety and the tolerability of four different dosages of mRNA-3704, an experimental treatment.
mRNA-3704 has already received Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation by the FDA. It has also been given Orphan Drug Designation by the EMA.
It includes mRNA encoding of MUT and it is encapsulated with a lipid nanoparticle created by Modern. This therapy is administered intravenously. The hope is that it will help the body to restore the MUT enzyme that many MMA patients are missing. This therapeutic formulation is also being investigated in Moderna’s chikungunya program and Phase 1 trial results have been positive so far for this indication.
Preclinical data with mouse models has shown that the therapy allows expression of MUT within the liver. The mice treated with the therapy had improved weight gain and survival. Another notable finding was that when the dosing was increased, liver toxicity and inflammation did not increase for the mice.
The human trial will enroll patients who are at least one year old. All patients will complete an observational period, treatment period, as well as a follow-up period.
The first patient is currently in the observational period. After this period is complete, they will begin treatment with the therapy to help establish an acceptable dose. It will be exciting to see the outcome of this new trial!
You can read more about this new investigation here.