Written by Taylor Le | Edited by Josephine Chan
Photo by alexandre saraiva carniato
The progressive degeneration of the nervous system causes neuron function, brain structure, or the spinal cord to become weakened and compromised with time. Ataxia is a family of degenerative diseases that can impair muscle, balance, and speech coordination due to such neuronal damage. A particular type of ataxia that affects 1 in 50,000 individuals is Friedreich’s Ataxia (FA), a progressive and genetic disease that commonly manifests during childhood, with symptom onset beginning as early as 5 years of age. The signal usually received by muscles to generate movement is slowly impaired due to the thinning and degeneration of the spinal cord and peripheral nerve fibers. To an extent, the part of the brain that regulates coordination and muscle control (i.e., the cerebellum) may also be negatively affected by FA [1].
FA is the most common form of hereditary ataxia and is primarily an autosomal recessive disease, meaning both parents must have passed down two copies of a negatively affected FXN gene. Normally, the FXN gene is responsible for creating the Frataxin protein, which helps auxiliary proteins with energy production. It also maintains homeostatic levels (i.e., the ability to maintain an internally stable environment while facing external changes) that are essential for normal function. Two copies of a defective FXN gene disrupt and reduce normal frataxin production, and research has shown that this reduction may be responsible for the degenerative nature of the disease. Due to this, energy production of the spinal cord, peripheral nerve, heart muscle, and brain cells is not as efficient and the accumulation of toxic byproducts in these cells is critically dangerous for long-term function. Another possible side effect of FA is the buildup of mitochondrial iron, which can react with oxygen and result in unstable chemicals that can destroy cells (i.e., free radicals) contributing to oxidative stress [2].
Early symptoms of FA include poor balance, difficulty walking, and slurring and slowness of speech. As the disease progresses, speech becomes jerky and sensation in the arms and legs is slowly lost. Unfortunately, further disease progression may shorten life expectancy and eventually result in death. While there is no currently approved cure or treatment for FA, many therapeutic strategies and research have tried to combat the widespread degeneration including genetic and cell-based therapies, decreasing oxidative stress (i.e., decreasing the amount of high-energy, unstable, and damage-inducing cells in the body), and increasing cellular frataxin to restore optimal levels of energy production [3,4]. An emerging treatment investigated by Lynch et al. (2021) focuses on Omaveloxolone, a drug that has been shown to reduce oxidative stress and inhibit proinflammatory signaling, meaning that signals from the immune system in response to an irritant are inihibited, preventing lasting-damage on vital organs. Based on early clinical trials, Lynch reports that omaveloxolone treatment at multiple time points of the disease may slow the progression of FA by at least two years [5].
All in all, as the most common type of hereditary ataxia, more research should be done into the treatments for this disease. FA is not as well-examined when compared to other neurodegenerative diseases, yet discovering effective treatments that target multiple mechanisms and pathways of such diseases may be a top priority in the coming decades to mitigate and prevent disease progression and to increase life expectancy and quality of life.
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