Gene Transfer Using Virus Helps Mice With FA

Scientists in Madrid have successfully treated mice with Friedreich’s ataxia (FA) by transferring genes for the frataxin protein into their nervous systems, using a viral transporter.

FA is a progressive disease that causes weakness and incoordination. It results from mutations in the gene for frataxin, a protein needed for energy production in nerve cells.

When Filip Lim and colleagues at Autonoma University of Madrid injected human frataxin genes, encased in modified herpes simplex viruses, into the brainstems of frataxin-deficient mice, they found they had restored the animals’ ability to stay on a rotating rod.

Their functional recovery was “surprisingly complete,” the researchers say in their report, published in the June issue of Molecular Therapy.

They note that humans who are carriers of FA but have no symptoms of the disease only have about 40 percent of the normal level of frataxin, indicating that high-level frataxin restoration probably isn’t necessary.

Delivery of genes to the nervous system is perhaps the most challenging form of gene therapy, but the modified herpes simplex virus appears promising as a vehicle.

The investigators note that it naturally targets nerve cells when it causes an infection; that it’s large enough to carry a lot of therapeutic DNA; and that it doesn’t integrate into any of a cell’s chromosomes, which makes it safer than viruses that do.

“All therapeutic strategies aimed at alleviating neurodegeneration in FA and many other neurological conditions have failed so far,” the authors write, “emphasizing the need to explore other options, such as gene therapy.”

They also say new mice, developed by Mark Pook at Brunel University in the United Kingdom and colleagues, will provide better tools for future studies, because they have genetic mutations exactly like those that cause human FA and have a disease that more closely mimics the human one.