Methylmalonic Acidemia (MMA)
Methylmalonic acidemia (MMA) is a life-threatening metabolic disorder characterized by toxic accumulation of methylmalonic acid. Leveraging our pioneering efforts in MMA research, Protheragen is at the forefront of developing cutting-edge therapies to enhance the effective management of MMA. As your trusted partner in MMA drug development research, we provide unparalleled support to meet your research needs.
Introduction to Methylmalonic Acidemia (MMA)
Methylmalonic acidemia (MMA) represents a group of inherited autosomal recessive disorders characterized by defective metabolism of methylmalonyl-CoA, leading to toxic accumulation of methylmalonic acid (MMA) and related metabolites. The incidence of MMA is estimated to be 1 in 50,000 to 100,000 live births, with a wide range of clinical manifestations, including isolated MMA, vitamin B12-responsive MMA, and combined MMA with homocystinuria.
Fig.1 The metabolic pathway of methylmalonic acidemia (MMA). (Hakimzadeh Z, et al., 2024)
Pathogenesis of Methylmalonic Acidemia (MMA)
Methylmalonic acidemia (MMA) arises from genetic defects disrupting the mitochondrial methylmalonyl-CoA mutase (MCM) enzyme or cobalamin (B12) metabolism, leading to toxic accumulation of methylmalonic acid and propionyl-CoA derivatives. This metabolic blockade impairs energy production (TCA cycle dysfunction), induces oxidative stress, and causes multi-organ damage, particularly in the brain, kidneys, and liver, through mechanisms like hyperammonemia, mitochondrial toxicity, and protein hyperacylation.
Fig.2 The absence of the enzyme MMUT leads to accumulation of organic acids and mitochondrial abnormalities. (Keller S A, Luciani A., 2022)
Therapeutic Development for Methylmalonic Acidemia (MMA)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| SEL-302 | AAV-mediated gene therapy delivering functional MUT gene to hepatocytes | MUT gene | NCT05778877 | Phase I/II |
| mRNA-3705 | Lipid nanoparticle-encapsulated mRNA encoding human methylmalonyl-CoA mutase (MCM) | MCM enzyme replacement in hepatocytes | NCT04899310 | Phase I/II |
| Carglumic Acid | Synthetic analog of N-acetylglutamate that activates carbamoyl phosphate synthetase 1 | N-acetylglutamate synthase | NCT05040178 | Approved |
| N-carbamylglutamate | Activates carbamoyl phosphate synthetase 1 to reduce ammonia levels | Urea cycle | NCT01597440 | Phase II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
As a leader in rare neurometabolic disease research, Protheragen offers comprehensive preclinical services to advance methylmalonic acidemia (MMA) therapeutics from discovery to validation. Our specialized platforms integrate genetic analysis and disease-specific modeling to replicate disease pathology with high fidelity. Using advanced blood-brain barrier (BBB) models, we optimize central nervous system (CNS) drug delivery while evaluating neuroprotection and off-target effects.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- MMUT Knockout Model
- MMACHC Knockout Model
- Mmaa Knockout Model
- Mut Conditional Knockout Model
- High Propionate Diet-Induced Model
- Other Models
To advance the commercialization of novel therapies for methylmalonic acidemia (MMA), Protheragen provides comprehensive preclinical research services, covering pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Hakimzadeh Z, Gilani A, Yousefichaijan P, et al. Acute fatal ventricular arrhythmia induced by severe hyperkalemia in a toddler with decompensated methylmalonic acidemia[J]. Journal of Medical Case Reports, 2024, 18(1): 73.
- Keller S A, Luciani A. Mitochondrial distress in methylmalonic acidemia: novel pathogenic insights and therapeutic perspectives[J]. Cells, 2022, 11(19): 3179.