Acetyl Tub


The patient-focused research at the Merritt Center spans from clinical characterization of affected individuals to histological analyses of muscle and the nervous system, molecular genetics investigations, and studies of cellular and animal models.

Merritt Center investigators have identified novel diseases and the molecular causes of dozens of rare neuromuscular disease including:

  • carnitine palmitoyl transferase 2 (CPT2) deficiency (DiMauro disease) 
  • phosphoglycerate mutase (PGM) deficiency 
  • phosphoglycerate kinase (PGK) deficiency  
  • adult polyglucosan body disease (APBD) 
  • mitochondrial DNA (mtDNA) single deletions as causes of chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome 
  • mtDNA depletion syndrome 
  • mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome  
  • TYMP pathogenic variants responsible for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) 
  • SCO2 defects causing cardioencephalomyopathy with cytochrome c oxidase (COX) deficiency  
  • LAMP2 pathogenic defects in Danon disease 
  • The first mutations responsible for coenzyme Q10 biosynthesis (COQ2 and PDSS2 pathogenic variants) 
  • Scapuloperoneal myopathy due to FHL1 defects 
  • RMND1 pathogenic variants as a cause of mitochondrial protein synthesis defect 
  • ribonucleotide reductase deficiency due to RRM1 defects 
  • A recurrent USMG5 pathogenic variant causing of Leigh Syndrome

Defects of mitochondrial DNA maintenance

The Merritt Center identified the first defect of nucleoside/nucleotide metabolism responsible for maintenance of mitochondrial DNA and continues to identify and investigate disorders in this pathway using cellular and animal models. Our deoxynucleoside therapy for thymidine kinase 2 deficiency (TK2d) was developed in a mouse model and is currently under investigation in a phase 2 clinical trial.

Coenzyme Q10 deficiency

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial respiratory chain responsible for producing most of the ATP energy required to drive cellular functions. Our research studies are investigating the causes and treatment of CoQ10 deficiency.

Adult polyglucosan body disease (APBD)

A rare genetic disease, APBD is most frequently observed among people of Ashkenazi Jewish ancestry and presents with urinary voiding problems, spasticity, and peripheral neuropathy. The Merritt Center has been investigating mouse models and testing therapies in patients.

Dysfunction of the Mitochondria-associated endoplasmic reticulum membranes (MAM)

A lipid raft-like subdomain of cells, MAM plays a central role in lipid metabolism. Merritt Center investigators have identified defects of MAM lipid processing that are pivotal to the pathogenesis of neurodegenerative processes including Alzheimer disease.

Digital Biology for rare neuromuscular and mitochondrial diseases

Investigators at the Merritt Center are developing artificial intelligence (AI)/machine learning (ML) techniques to power new discovery platforms to drive the identification of novel disease genes as well as therapeutic options, e.g. by virtue of high-throughput, microscopy-based profiling of patient cells.

Clinical Trials

The Merritt Center has led investigator-initiated treatment trials as well as participated in industry-sponsored clinical trials for disorders of glycogen metabolism and mitochondrial diseases.

North American Mitochondrial Disease Consortium (NAMDC)

Merritt Center investigators initiated and lead NAMDC, a network of 16 academic sites with mitochondrial disease expertise, focused on diagnosing and characterizing mitochondrial diseases, clinical trial readiness, biobanking of blood samples from mitochondrial disease research subjects, and education of the next-generation of mitochondrial disease translational investigators.

Research Affiliates

The Merritt Center collaborates with investigators and research programs across Columbia as well as across the United States and abroad to enhance our efforts to understand and treat rare neuromuscular and mitochondrial diseases.