A synthetic molecule developed by UT Southwestern research scientist David Corey’s laboratory may soon treat a rare, incurable genetic disease.
Friedreich’s ataxia is a progressive genetic neuromuscular disease that causes chronic fatigue, balance issues, slurred speech and eventually fatal heart problems. The Corey Lab is working on a treatment to bring hope to patients affected by FA.
FA is caused by a DNA mutation that interrupts the creation of frataxin, a protein located in the mitochondria. The sequence for frataxin repeats too many times, which creates unusable protein in place of frataxin. This frataxin deficiency affects the mitochondria and reduces the energy that is available for the cell.
Corey’s laboratory developed a synthetic molecule, called an oligonucleotide, that is designed to fix the root cause of FA. This molecule allows the cell to create frataxin normally.
“The beauty of the oligonucleotide approach is that it has a certain sequence, and that sequence can match up with a specific gene,” Corey said. “We get more RNA, hence more protein, and more frataxin protein has a chance of making patients better.”
Researchers have also investigated the possibility of gene therapy, by which doctors would insert a healthy frataxin gene into a patient’s cell. However, gene therapy is more difficult, while synthetic molecules are already widely tested, according to Corey.
“Those types of compounds are already being administered into the central nervous system of patients, and they’re actually already beginning to show some favorable effects in patients who have other diseases,” he said.
There is no cure or treatment currently available for FA, according to Jen Farmer, executive director of the Friedreich’s Ataxia Research Alliance, a fundraising organization that gave Corey Lab a research grant.
“It really is just sort of managing the symptoms and adjusting and adapting to the physical loss,” Farmer said. “We’re hoping that we have treatments in the near term that can at least slow or maybe stop the progression of this disease.”
Kendall Harvey, an Austin woman with FA and a fundraiser for FARA, said even though she has a milder case, she will probably be using a wheelchair by age 50.
“That’s a hard pill to swallow, but there’s so much research going on and so many advancements being made,” Harvey said. “I’m just doing anything and everything I can to raise awareness and funds for FARA so that the right minds can get the support they need to cure this thing.”
Harvey hopes that a cure will happen soon so it will end the progression of her disease.
However, Corey said although his research and the research of others is promising, the oligonucleotide treatment is far from ready for clinical trials. Corey said they could consider clinical trials within the next five to ten years.
“This is a promising basic research discovery, and the general advancement of the field of oligonucleotides is promising, but nothing is going to happen right now,” he said. “Drug discovery is hard, and we’re at the start of a long road.”
Corey said he hopes his work and the ongoing research for a cure encourages people with FA.
“This is a tough disease for people to live with, I hope that they can look at work like this and have at least a little hope,” he said.