Recent advances towards gene therapy for propionic acidemia: translation to the clinic

Research output: Contribution to journalReview article

Abstract

Introduction: Propionic acidemia (PA) is a metabolic genetic disease that occurs in 1 in 100,000 live births in United States and up to 1 in 3,000 in certain populations. PA is caused by deficiency in either the α or β subunits of the mitochondrial enzyme propionyl CoA carboxylase (PCC), encoded by the PCCA and PCCB genes. This disease causes metabolic acidosis, ketosis, vomiting, lethargy, cognitive reductions, and death. There is no cure for PA. Areas covered: This review discusses the genetics and biology of PA in humans. The development of mouse models of the disease is discussed. The use of gene therapy as a replacement for elective liver transplantation is proposed. The strategies, challenges, and preclinical results of gene therapy are detailed in the review. Expert opinion: Gene therapy for propionic acidemia in humans is feasible. Regardless of the payload, gene, mRNA, or genome editing approaches will stand or fall based on their ability to hit the right tissue targets. Therapies that target only the liver will be an improvement to elective liver transplantation, but will neglect repairing damage in at-risk tissues like the brain and the heart.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalExpert Review of Precision Medicine and Drug Development
Volume4
Issue number4
DOIs
StatePublished - Jan 1 2019

Fingerprint

Propionic Acidemia
Genetic Therapy
Liver Transplantation
Methylmalonyl-CoA Decarboxylase
Lethargy
Ketosis
Inborn Genetic Diseases
Aptitude
Metabolic Diseases
Expert Testimony
Live Birth
Acidosis
Vomiting
Messenger RNA
Liver
Brain
Enzymes
Population
Genes

Keywords

  • adeno-associated virus vectors
  • adenovirus vectors
  • gene therapy
  • genome editing
  • liver transplantation
  • Propionic acidemia
  • tissue targeting

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Recent advances towards gene therapy for propionic acidemia : translation to the clinic. / Barry, Michael A.

In: Expert Review of Precision Medicine and Drug Development, Vol. 4, No. 4, 01.01.2019, p. 229-237.

Research output: Contribution to journalReview article

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