When gene therapy company Asklepios BioPharmaceutical, Inc. (“AskBio”) and biotechnology company Selecta Biosciences (“Selecta”) joined forces to combat genetic disorders, each company brought its best technology and insights. AskBio assisted with the creation of an AAV gene therapy program, while Selecta used its proprietary ImmTOR platform to address immunogenicity in relation to gene therapy. Now, the companies have announced that their gene therapy candidate MMA-101, designed for patients with methylmalonic acidemia (MMA), received Orphan Drug designation in the United States.

MMA-101

Overall, MMA-101 is designed specifically for patients with mutated MUT genes. This specific gene mutation is responsible for nearly 60% of MMA diagnoses. Normally, the MUT gene instructs the body to create methylmalonyl CoA mutase, a type of enzyme. In conjunction with vitamin B12, this enzyme breaks down cholesterol, lipids, and amino acids. But MUT mutations prevent these from being broken down; the resulting accumulation causes damage and toxicity.

In October 2020, this gene therapy received Rare Pediatric Disease designation. Both this designation, and the recently acquired Orphan Drug designation, are designed to incentivize drug developers to create new therapies for patients with rare diseases. Typically, rare diseases are defined as those affecting under 200,000 American citizens. While Orphan Drug designation is granted to investigational therapies for rare diseases, Rare Pediatric Disease designation is saved for those affecting mostly pediatric patients (18 years old or younger). Orphan Drug designation also comes with benefits such as seven years of market exclusivity, tax credits, fee waivers, and increased communication. Moving forward, AskBio and Selecta hope to hold a Phase 1 clinical trial for MMA-101 and ImmTOR in 2021.

Methylmalonic Acidemia (MMA)

Because methylmalonic acidemia is inherited in an autosomal recessive manner, patients must inherit one mutated gene from each parent. While a majority of MMA cases result from MUT gene mutations, the condition can also result from MMAA, MCEE, MMADHC, and MMAB mutations.

MMA is a subtype of organic acidemia. In short, patients with these conditions are unable to process specific fats and proteins. The mutations cause enzymatic defects which affect methionine, valine, isoleucine, and threonine. As a result, the body tissue and blood experience high acid levels. Typically, patients with MMA will show symptoms within a few months of birth. These symptoms include:

• Low blood sugar
• Anemia (low red blood cell count)
• Neutropenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Nausea and vomiting
• Seizures
• Fatigue and drowsiness
• Developmental and intellectual delays
• Difficulty breathing
• Dehydration
• Liver enlargement
• Acidosis