Gene therapy for inherited metabolic disorders in companion animals.

Scientists first described inborn errors of metabolism, also termed inherited disorders of metabolism, early in the 20th century and since then have determined the biochemical and genetic bases of a great number of these disorders both in humans and in an increasing number of companion animals. The availability of metabolic screening tests has advanced the biochemical and genetic characterization in affected breeds of companion animals of inherited metabolic disorders involving amino acid, carbohydrate, fatty acid, and metal metabolism. Advances in gene therapy have led to the development of new treatments for inherited disorders of metabolism, and animal models have played a critical role in this research. For example, glycogen storage disease type Ia in dogs was highly responsive to adeno-associated viral vectormediated gene therapy, which prolonged survival and for more than a year prevented hypoglycemia during fasting. Gene therapy for other glycogen storage diseases and metabolic disorders will also be feasible. The establishment of a breeding colony and the ability to sustain affected animals are critical steps toward evaluating the safety and efficacy of gene therapy with clinically relevant endpoints. The further development of gene therapy for inherited disorders of metabolism could lead to curative therapy for affected humans and animals alike.

Duke Scholars

Author Dwight D. Koeberl Pediatrics, Medical Genetics

Author Yuan-Tsong Chen Pediatrics, Medical Genetics