by Samitha NemirajaiahFriedreich’s ataxia (FA) is a “rare and progressive autosomal recessive neurodegenerative disease” (Pandolfo, 2008). Friedreich’s ataxia disease is named after Nicholaus Friedreich, who is the Professor of Medicine in Heidelberg, Germany. Approximately 4,000 patients in the U.S. and 15,000 people globally are affected by Friedreich’s ataxia. Unfortunately, there is no cure or treatment for Friedreich’s ataxia, resulting in a life expectancy of about 30-50 years of age (Pandolfo, 2008). Friedreich’s ataxia is caused by a defective gene called FXN, which is responsible for frataxin (FXN) protein level in cells’ mitochondria. The lower level of frataxin is caused by GAA repeat expansion mutations inside intron 1 of the Frataxin gene. The lower level of frataxin results in mitochondria oxidative stress causing the disease. Every person has two copies of the FXN gene, and the FXN gene has five genetic parts called exons. With GAA trinucleotide Intron between them, together they form frataxin protein. For normal operation, the repetition of the number of GAA trinucleotide intron between exons determines whether the gene functions normally and enough Frataxin protein is produced. The frataxin gene has five compartments, and the following is a graphical representation of frataxin protein consisting of five different exons (Piguet et al., 2018). In a defective setup, the GAA trinucleotide intron repeats why more than normal, resulting in less production of frataxin protein. In patients with Friedreich’s ataxia, the GAA trinucleotide intron repeats 100-1500 times more compared to normal. The more the repetition lesser the Frataxin protein level in the cell mitochondria, which reduces the engine output, meaning the Frataxin production is reduced, causing Friedreich’s ataxia (Piguet et al., 2018). The symptoms generally start between the age of 5-18 years and consist of unsteady posture, frequent falling, and difficulty in walking. Friedreich’s ataxia causes major heart damage Hypertrophic Cardio Myopathy resulting in early death by heart disease. Friedreich’s ataxia patients have less frataxin (FXN) protein in their mitochondria cells compared to normal human beings (50% of normal level). Current treatments do not directly treat the diseases but treat some of the symptoms caused by the disease. Genetic testing is used to determine FA. Currently, fourteen clinical trials are ongoing to find treatment for Friedreich’s ataxia. Various Mechanism of Action (MOA), through which a treatment specifically targets, are used to increase the level of frataxin protein in cell mitochondria The main pathway is to increase the level of Frataxin protein. The Food and Drug Administration (FDA) has accepted frataxin as a biomarker for Friedreich’s ataxia (FA) disease (“Fara - Research Pipeline,” n.d.). As illustrated in the treatment pipeline (Figure 3), all the clinical trials are still in development, resulting in no current approved treatment for FA. Some of the clinical trials are in Phase 3, and some are in pre-clinical development. While the trials are in different levels of development, the common goal of different treatments is to increase the level of frataxin in the cell. Some treatments do not directly treat the disease but treat some of the symptoms caused by the disease, possibly increasing the quality of life for patients but not curing them. Genetic testing is used to determine Friedreich’s ataxia, and several companies offer genetic testing. Finding a treatment for Friedreich’s ataxia will be of immense help to improve patients’ quality of life and save patients’ lives (“Fara - Research Pipeline,” n.d.). References
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