• By Susan Murphy

Mayo researchers reveal gene therapy path for treating children with rare, fatal genetic disease

April 7, 2021
3d medical illustration of chromosomes representing gene therapy

A gene therapy strategy developed by Mayo Clinic researchers could offer a potential treatment for a rare and fatal genetic disease that often sickens babies in their first days of life. The disease, propionic acidemia, occurs in 1 in 100,000 live births in the U.S. There is no cure.

"As soon as the babies start eating, they quickly get sick," says Michael Barry, Ph.D., a gene therapy expert within Mayo Clinic's Division of Infectious Diseases. "They can start vomiting, become lethargic and have seizures. They have metabolic acidosis (electrolyte disorder) and particularly hyperammonemia (excess of ammonia in the blood), which is very dangerous. And if they are not treated, they can die."

Dr. Barry and his team with Mayo Clinic's Center for Individualized Medicine have developed a technique to replace the defective genes that cause the disease. Dr. Barry will present his gene therapy strategy at the upcoming Undiagnosed Disease Network International and Mayo Clinic Science Session April 9–11. 

Propionic acidemia is caused by an inherited mutation in the PCCA or PCCB genes, which provide instructions for making the enzyme propionyl-CoA carboxylase. This critical enzyme, which is used by many cells in the body, plays a role in breaking down amino acids, as well as certain lipids, or fats, and cholesterol. A deficiency in this enzyme leads to a buildup of toxic chemicals.

In most cases, patients are given a special protein-restricted diet that can limit life-threatening episodes, but this is difficult and does not cure the disease. Current treatment options are limited and do not provide the quality of life or long-lasting benefits that patients and their families are seeking. In some cases, a liver transplant is a potential treatment, but this has its own risks.

"Our approach is to give these patients a good copy of the gene to counteract the disease as best we can," explains Dr. Barry, who has devoted 15 years to studying propionic acidemia. "This restores the ability of cells in the body to process these food components and reduce the production of toxic chemicals."

Read the rest of the article on the Center for Individualized Medicine blog.

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