Rare Disease Highlight: Spinocerebellar Ataxia

Spinocerebellar ataxia (SCA) is a group of autosomal dominant, progressive neurodegenerative disorders, mainly affecting the cerebellum and/or brain stem (Sullivan et al., 2019).Ataxia is also known as impaired coordination due to damage to the brain, nerves, or muscles. Since SCA is inherited in an autosomal dominant pattern, one parent can pass the mutation to the child, with symptoms observable as early as birth (NAF, 2015). Generally, patients with SCA present with 3 core features (Sullivan et al., 2019):

  1. Ataxic gait – difficulty walking in a straight line, incoordination, veering side-to-side, widened stance for better base support, and inconsistent arm motion.
  2.  Nystagmus/visual problems – involuntary rhythmic eye motions.
  3. Dysarthria – weakened muscles causing slurred speech.

Specific subtypes of SCA can also manifest other symptoms in the trunk and/or limbs (Sullivan et al., 2019):

  1. Extrapyramidal and pyramidal signs – involuntary movements (such as tremors and muscle contractions) and abnormal reactions to external stimuli upon neurological examination, respectively.
  2. Ophthalmoplegia – paralysis of muscles controlling eye movements.
  3. Cognitive impairments, including intellectual disability or dementia.

In the most common subtypes of SCA, a CAG (cytosine, adenine, and guanine) trinucleotide repeat in a specific gene causes an expansion in certain proteins (Pilotto et al., 2018). Nucleotides are the basic units composing deoxyribonucleic acid (DNA). Therefore, a trinucleotide repeat refers to the presence of three nucleotides consecutively repeated within a specific region of the DNA. As a result, these proteins misfold and accumulate in neuronal cells within the cerebellum or spinal cord. The affected neurons progressively become dysfunctional and begin to degrade, manifesting as ataxia (Pilotto et al., 2018). The cause of other SCA subtypes are based on specific genetic variations (Sullivan et al., 2019).

SCA is a physically debilitating disease, leaving patients unable to execute activities of daily living without assistance. As the disease progresses in severity, patients can lose neurological function, potentially leading to intellectual disability, slurred speech, or death from complete brainstem failure. Survival can range from 8 years after symptom onset to a normal lifespan (O’Sullivan et al., 2004). In the most common SCA subtypes, patients are expected to survive for a few decades following initial onset of symptoms (O’Sullivan et al., 2004; Tezenas du Montcel et al., 2014). However, severe cases of subtypes SCA2, SCA3, SCA7, SCA16, and SCA17 have the shortest survival (O’Sullivan et al., 2004). Overall patient prognosis is determined by the length of CAG repeat expansion (Pilotto et al., 2018).

Currently, there is no cure for SCA, so supportive care for symptomatic relief is the goal of treatment. To manage ataxia, patients participate in physical therapy to preserve muscle strength and tone. In addition, patients might receive special mobility-assisting devices, such as a walkers, canes, or wheelchairs. For symptoms such as tremors, muscle stiffness, muscle spasms, and sleep disorders, medications are prescribed as needed (GARD, 2022). SCA patients are recommended to have consistent, long term follow-up with their healthcare professionals to monitor and prevent complications in the heart, lungs, spine, bones, and/or muscles (NORD et al., 2022). Thus, despite available standard of care for symptom management, an unmet medical need for a novel therapy exists for SCA patients.


GARD. (2022, 2017). Spinocerebellar Ataxia. Retrieved 4/25/2022 from https://rarediseases.info.nih.gov/diseases/10748/spinocerebellar-ataxia.

NAF. (2015). Classification of Ataxia. National Ataxia Foundation. Retrieved from https://www.ataxia.org/wp-content/uploads/2019/04/Ataxia-Classification.pdf

NORD, & Bird. (2022, 2017). Autosomal Dominant Hereditary Ataxia. Rare Disease Database. Retrieved 4/25/2022 from https://rarediseases.org/rare-diseases/autosomal-dominant-hereditary-ataxia/.

O’Sullivan, Michelson, Bennett, & Bird. (2004). Spinocerebellar Ataxia: Making an Informed Choice About Genetic Testing. Medical Genetics and Neurology. Retrieved from https://www.ataxia.org/wp-content/uploads/2017/07/SCA-Making_an_Informed_Choice_About_Genetic_Testing.pdf

Pilotto, & Saxena. (2018). Epidemiology of inherited cerebellar ataxias and challenges in clinical research. Clinical and Translational Neuroscience, 2(2), 2514183X18785258. doi:10.1177/2514183×18785258

Sullivan, Yau, O’Connor, & Houlden. (2019). Spinocerebellar ataxia: an update. Journal of neurology, 266(2), 533-544. doi:10.1007/s00415-018-9076-4

Tezenas du Montcel, Durr, Rakowicz, Nanetti, Charles, Sulek, Mariotti, Rola, Schols, Bauer, Dufaure-Garé, Jacobi, Forlani, Schmitz-Hübsch, Filla, Timmann, van de Warrenburg, Marelli, Kang, Giunti, Cook, Baliko, Bela, Boesch, Szymanski, Berciano, Infante, Buerk, Masciullo, Di Fabio, Depondt, Ratka, Stevanin, Klockgether, Brice, & Golmard. (2014). Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6. Journal of Medical Genetics, 51(7), 479-486. doi:10.1136/jmedgenet-2013-102200

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with a unmet medical needs. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

Comments are closed.