Puccio Study FA

A recent breakthrough in Friedreich’s ataxia (FA) research gives hope that gene therapy can prove be an effective treatment for the disease. A team led by Hélène Puccio, Ph.D., has demonstrated that gene therapy can be used to reverse heart damage caused by FA and correct mitochondrial metabolism. Dr. Puccio works as the head of a research team at the Institute of Genetics and Molecular and Cellular Biology located at the University of Strasbourg, France, as well as research director at the Insititute de Santé et de la Recherche Médicale (INSERM.) She and her team have concentrated their research on the pathophysiological mechanisms involved in recessive ataxias, like FA, in order to develop new animal and cell models.

Friedreich’s ataxia is rare, but one of the more common recessive ataxias – found in 1 in every 50,000 births. It is caused by a mutation in the frataxin (FXN) gene, which in turn causes a decrease in the amount of frataxin produced. The lack of frataxin disrupts the mitochondria that are responsible for the cell’s energy production, and, unfortunately, heart tissue is particularly vulnerable.

While FA causes progressive neurodegeneration that starts as impaired balance and coordination, it also impairs heart function and can contribute to diabetes. Most patients require a wheelchair after about 10-20 years of disease progression, but complications with the heart lead to death in more than half of individuals, and often before the age of 35.

Dr. Puccio’s team used a harmless viral vector to insert a normal copy of the problematic gene in the heart cells of FA mouse models. Since these mice show the same heart symptoms as human patients suffering from the disease the results are especially promising. The virus used was an adeno-associated virus (AAV) since it is known to effectively and efficiently target heart cells and express therapeutic diseases. This virus was modified to render it harmless and only capable of inserting the normal FXN gene copy into the cells.

One single intravenous injection was not only able to prevent the development of heart disease in the mice, but it quickly and completely reversed the heart damage in advanced cases. Within three weeks the mice appeared to have completely restored heart and mitochondrial function and their heart tissue appeared similar to healthy mice.

Since this is the first time that gene therapy has produced such a fast and complete remission of heart disease in an animal model work is rapidly being done to begin clinical studies. There is also hope that this technique can be used to prevent or even correct damage to the spinal cord and cerebellum.