ACSF3-based Diagnostics and Therapeutics for Combined Malonic and Methylmalonic Aciduria (CMAMMA) and Other Metabolic Disorders

Combined malonic and methylmalonic aciduria (CMAMMA) is a metabolic disorder in which malonic acid and methylmalonic acid, key intermediates in fatty acid metabolism, accumulate in the blood and urine. This disorder is often undetected until symptoms manifest, which can include developmental delays and a failure to thrive in children, and psychiatric and neurological disorders in adults. Once thought to be a very rare disease, CMAMMA is now thought to be one of the most common forms of methylmalonic acidemia and, perhaps, one of the most common inborn errors of metabolism, with a predicted incidence of one in 30,000.

Investigators at the National Human Genome Research Institute have identified the genetic cause of CMAMMA, an enzyme encoded by the ACSF3 (Acyl-CoA Synthetase Family Member 3) gene. This enzyme is located in the mitochondrion and appears to be a methylmalonyl-CoA and malonyl-CoA synthetase, which catalyzes the first step of intra-mitochondrial fatty acid synthesis. As such, this discovery may not only be critical for the development of diagnostic tools and treatments for CMAMMA, but also holds promise for the treatment of other related metabolic disorders.

Potential Commercial Applications: Competitive Advantages:
  • Diagnosis of CMAMMA or other metabolic diseases
  • Therapies for CMAMMA or other metabolic diseases, such as lipoic acid administration, gene therapy or enzyme replacement therapy
  • Mutation of ACSF3 has been shown to be the genetic cause of CMAMMA and there are no existing methods to diagnose this disorder.
  • Therapies based on ACSF3 may be applicable to a variety of metabolic disorders.

Charles Venditti (NHGRI)
Leslie Biesecker (NHGRI)
Jennifer Sloan (NHGRI)
Jennifer Johnston (NHGRI)
Eirini Manoli (NHGRI)
Randy Chandler (NHGRI)

Intellectual Property:
US Application No. 61/504,030
PCT Application No. PCT/US12/44926

Licensing Contact:
Vince Contreras , Ph.D.
NIH Office of Technology Transfer
Phone: 301-435-4711

OTT Reference No: E-209-2011/0

Updated: Aug-30-2013