Children born with propionic acidemia require life-long treatment and care; without it, this disorder can lead to coma or even death. While there are supportive treatment options, no current therapies address the underlying cause of propionic acidemia. Biotechnology company Moderna is working to overcome that through the development of mRNA-3927, a novel lipid nanoparticle-encapsulated dual mRNA therapy. Delivered intravenously, mRNA-3927 addresses the PCCA and PCCB mutations that lead to propionic acidemia. 

Moderna recently shared interim data from a Phase 1/2 trial at the ASGCT 26th Annual Meeting, which took place from May 16-20, 2023. Within this study, researchers are working to determine how safe and effective mRNA-3927 is, as well as its pharmacokinetic profile, in those with propionic acidemia who are ages 1+. So far, 16 participants have been dosed with mRNA-3927. Of these, 68.75% have continued on to the open-label extension (OLE). 

So far, mRNA-3927 has been relatively well-tolerated with no issues with toxicity. Participants reported fewer (or no) metabolic decompensation events after receiving treatment. Some side effects did occur, with the most common being infusion-related reactions. 

Propionic Acidemia: What You Need to Know

Existing under the greater umbrella of organic acidemia, propionic acidemia is a rare inherited metabolic disorder. This condition is caused by PCCA and PCCB gene mutations, which cause the body to be deficient in propionyl CoA carboxylase. Normally, this enzyme breaks down certain amino acids. As various substances accumulate in the blood to a toxic level, a number of health issues occur. 

Symptoms of propionic acidemia normally appear within the first few days or weeks of a child’s life. These may include:

• Appetite loss
• Vomiting
• Lethargy
• Low muscle tone (hypotonia)
• Poor feeding
• Dehydration
• Failure to thrive
• Seizures 

As a child grows older, their symptoms may also progress to include some of the following:

• Thrombocytopenia (low platelet count) 
• Constipation
• Intellectual disability
• Osteoporosis
• Cardiomyopathy
• Pancreatitis
• Chronic renal failure 
• Anemia (low red blood cell count)
• Leukopenia (low white blood cell/leukocyte count) 

Treatment options include fluid therapy, a low-protein diet to avoid metabolic crisis, biotin or carnitine supplementation, hemodialysis, and (in severe cases) liver transplantation.