Friedreich Ataxia (FA)

Rare, inherited, progressive disease resulting from mitochondrial dysfunction

What is Friedreich Ataxia?

Friedreich ataxia (FA) is a rare, physically debilitating, life-shortening, neuromuscular disorder that mainly affects the central nervous system and the heart.¹ It is the most common hereditary ataxia (abnormal, uncoordinated movements) and is usually caused by a single genetic defect in the frataxin (FXN) gene that leads to reduced production of frataxin, a mitochondrial protein that is important for cellular metabolism and energy production.^1,2 Decreased frataxin levels are associated with mitochondrial iron accumulation and increased oxidative stress, which can lead to cell death through ferroptosis.^3,4,5

Symptoms include progressive loss of coordination and muscle strength leading to poor balance and coordination, difficulty speaking, swallowing, and breathing, curvature of the spine, serious heart conditions, diabetes, and hearing and vision impairment.^6,7 The severity of symptoms and speed of progression varies between people and some symptoms may not be evident in all. Friedreich ataxia is usually diagnosed in childhood or adolescence.^2,8

How Common is Friedreich Ataxia?

Approximately 25,000 people have Friedreich ataxia globally. Men and women are equally affected.

How is PTC Working to Treat Friedreich Ataxia?

PTC is developing vatiquinone, a potential treatment for Friedreich ataxia based on our Ferroptosis & Inflammation platform. Vatiquinone is a small molecule, first-in-class selective inhibitor of 15-Lipoxygenase (15-LO), an enzyme that is a key regulator of the energetic and oxidative stress pathways that are disrupted in Friedreich ataxia. Inhibition of 15-LO helps to alleviate the consequences of mitochondrial dysfunction and oxidative stress, ultimately preventing ferroptosis and aiding neuronal survival.^9,10,11 Vatiquinone has been evaluated in a number of clinical studies and has demonstrated an impact on mortality risk and a number of neurological and neuromuscular disease symptoms.

References

[1] Lynch DR, Farmer JM, Balcer LJ, et al. Arch Neurol 2002;59(5):743–747.

[2] Campuzano V, Montermini L, Lutz Y, et al. Hum Mol Genet 1997;11(6):1771–1780.

[3] Campuzano V, et al. Hum Mol Genet. 1997;6:1771–1780.

[4] Cook A, Giunti P. Br Med Bull. 2017;124:19–30.

[5] Pandolfo M, Hausmann L. J Neurochem. 2013;126:142–146.

[6] Bürk K. Cerebellum Ataxias 2017;4:4.

[7] Cook A, Giunti P. Br Med Bull 2017;124(1):19–30.

[8] Delatycki MB, Williamson R, Forrest SM. J Med Genet 2000;37(1):1–8.

[9] Hinman A, et al. PLoS one. 2018;13:e0201369.

[10] PTC Therapeutics. EPI-743 Pre-Clinical Data Deck.

[11] Shrader WD, et al. Bioorg Med Chem Lett. 2011;21:3693–3698.

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