Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency

Abstract

Autosomal recessive human thymidine kinase 2 (TK2) mutations cause TK2 deficiency, which typically manifests as a progressive and fatal mitochondrial myopathy in infants and children. Treatment with pyrimidine deoxynucleosides deoxycytidine and thymidine ameliorates mitochondrial defects and extends the lifespan of Tk2 knock‐in mouse (Tk2KI) and compassionate use deoxynucleoside therapy in TK2 deficient patients have shown promising indications of efficacy. To augment therapy for Tk2 deficiency, we assessed gene therapy alone and in combination with deoxynucleoside therapy in Tk2KI mice.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 13, 2021
Source ID
10.1002/ana.26185

Entities

People

  • Carlos Lopez‐gomez
  • Eung Jeon Lee
  • Giulio Kleiner
  • Guangping Gao
  • Hasan Orhan Akman
  • Jun Xie
  • Maria J. Sanchez‐quintero
  • Michio Hirano
  • Saba Tadesse

Organizations

  • Columbia University
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • J. Willard and Alice S. Marriott Foundation
  • United States Department of Defense
  • University of Massachusetts

Tags

Fields of Study

  • Biology
  • Medicine

Readers

  • Cardiovascular Physiology
  • Molecular Genetics
  • Molecular and Cellular Biology

Technology Areas

  • Biotechnology