Maple Syrup Urine Disease (MSUD)
The greatest difficulty in overcoming maple syrup urine disease (MSUD) is crafting effective interventions to restore metabolism of branched-chain amino acids without incurring irreversible neurological damage in neonatal-onset cases during metabolic crises. Drawing from our extensive experience in developing MSUD therapies, Protheragen is strategically positioned to offer tailored solutions to expedite your progress from MSUD therapy development to commercial transition.
Introduction to Maple Syrup Urine Disease (MSUD)
Maple syrup urine disease (MSUD) is a disorder of branched-chain amino acids (BCAA) metabolism whose key features include life-threatening and exhibiting an autosomal recessive inheritance pattern. The underlying defect is in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, whose activity is disrupted. If left untreated, the toxic build-up of leucine, isoleucine, valine, and their α-keto acid derivatives leads to profound neurological damage and metabolic decompensation.
Fig.1 Muscle-directed AAV gene therapy rescues the maple syrup urine disease (MSUD) phenotype in a mouse model. (Jenny A. Greig, et al., 2021)
Pathogenesis of Maple Syrup Urine Disease (MSUD)
Mutations in the BCKDHA, BCKDHB, or DBT genes cause the MSUD (Maple syrup urine disease) due to the lack of BCKDH (branched-chain α-ketoacid dehydrogenase) complex activity. This leads to toxic accumulation of branched-chain amino acids (leucine, isoleucine, valine) and their corresponding ketoacid derivatives. This accumulation disrupts energy metabolism in the brain, causes neurotoxic edema, inflicts oxidative stress, and if not treated, leads to severe untreated neurological damage.
Therapeutic Development for Maple Syrup Urine Disease (MSUD)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Phenylbutyrate | Nitrogen scavenger that reduces branched-chain amino acid (BCAA) levels via alternative excretion pathways | Urea cycle | Phase II/III |
| Thiamine | Cofactor for residual BCKDH complex activity in thiamine-responsive MSUD variants | BCKDH complex | Approved |
| N-acetylcysteine | Antioxidant that replenishes glutathione and mitigates oxidative stress during metabolic crises | Reactive oxygen species (ROS) in neurons | Early research |
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
To improve the management of the maple syrup urine disease (MSUD), Protheragen provides diagnostic and therapeutic development services, supporting some of our innovative deep expertise and modern technologies. We are focused on the MSUD molecular mechanisms and on the innovative therapies aimed at the high unmet medical needs. Our experts succeed in the development of highly accurate disease models which enables the preclinical evaluation of the safety and efficacy of potential therapeutics.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- BCKDHA or BCKDHB Knockout (KO) Models: Complete deletion of Bckdha or Bckdhb genes, mimicking human MSUD types 1A & 1B.
- DBT Knockout (KO) Model: Loss of dihydrolipoamide branched-chain transacylase (DBT), causing MSUD type 2.
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Jenny A. Greig, Matthew Jennis, et al. Muscle-directed AAV gene therapy rescues the maple syrup urine disease phenotype in a mouse model [J]. Molecular Genetics and Metabolism, 2021, 34: 139-146.