The FXN gene provides instructions for creating frataxin, a protein found throughout the body. Higher concentrations are present in organs like the heart, spinal cord, liver, pancreas, and skeletal muscles. Frataxin plays a role in maintaining the normal function of cells, especially in processes related to energy production.
The Biological Role of Frataxin
Frataxin is primarily located within the mitochondria, the cell’s “powerhouses.” Here, frataxin regulates iron levels. This regulation is particularly important for the assembly of iron-sulfur clusters. These clusters are like tiny “spark plugs” for many proteins, enabling them to carry out their functions, including those involved in cellular energy production.
Frataxin helps in the process of transferring sulfur to scaffold proteins, which is a step in building these iron-sulfur clusters. While its precise mechanism is still being studied, evidence suggests frataxin is involved in ensuring that iron is properly utilized and not allowed to accumulate in a way that could cause cellular damage.
Connection to Friedreich’s Ataxia
When the FXN gene contains mutations, it leads to a significant reduction in the amount of frataxin protein produced in cells. The most common mutation involves an abnormal expansion of a GAA trinucleotide repeat segment within the gene, typically repeated 66 to over 1,000 times, compared to fewer than 12 repeats in most individuals. This shortage of frataxin is the underlying cause of Friedreich’s Ataxia, a progressive neurodegenerative disorder.
People with Friedreich’s Ataxia experience a range of symptoms, including progressive difficulty with coordination and balance. Other characteristics can include slurred speech, muscle weakness, loss of sensation in the limbs, and an irregular curvature of the spine (scoliosis). The disorder can also affect the heart, causing a condition called hypertrophic cardiomyopathy. Symptoms usually begin between ages 5 and 15.
Current Research and Treatments
Current approaches to Friedreich’s Ataxia include managing symptoms through therapies like physical therapy to maintain muscle function. Medications may be used to address specific complications, such as heart conditions or diabetes. These supportive treatments aim to improve the quality of life for affected individuals.
Scientific research focuses on directly addressing the frataxin deficiency. Gene therapy strategies are being developed to deliver a healthy version of the FXN gene into cells, aiming to restore frataxin production. Drug development is exploring compounds designed to increase the body’s own production of frataxin protein or stabilize existing frataxin. These emerging therapies offer hope for slowing or potentially reversing the disease progression.