PROJECT SUMMARY:
Friedreich’s Ataxia (FA) is an inherited disorder that results in progressive degeneration of the nervous system and heart. The onset of symptoms of this debilitating condition occur in childhood or adolescence, and include loss of control of muscle movement, muscle wasting, deterioration of hearing, vision and speech, as well as heart disease and diabetes. The cause of this condition is a genetic mutation that leads to a disruption in the normal production of a cellular protein known as frataxin. In FA patients, the low levels of frataxin protein cause iron accumulation in cells leading to cellular toxicity. The cells which are particularly affected in FA include specific nerves within the brain and spinal cord as well as cardiac cells.
In order to develop effective treatments for FA, it would be tremendously useful to have human diseased cells in culture so that we may be able to understand the disease mechanisms and develop suitable drugs to counteract cell degeneration. To achieve this objective, we recently generated a population of stem cells from skin cells taken from Friedreich Ataxia patients, and showed that these stem cells can become nerves in the culture dish. These nerves exhibit the cellular hallmarks of FA disease. The aim of this project is to now characterize the electrical properties of these nerves using a technique known as patch-clamp electrophysiology. This will allow us to examine how cellular stress in FA influences the communication of these nerves. In addition, we will examine whether increasing the level of frataxin protein in diseased nerves will restore their electrical functional properties. These studies are very important for developing cellular models of Friedreich ataxia to aid the progression of drug discoveries and well as cell replacement therapies.
The Brain Foundation is the largest, independent funder of brain and spinal injury research in Australia. We believe research is the pathway to recovery.