This non-Mendelian inheritance is similar to that observed in Huntington's disease and is believed to be caused by differences in various mechanisms in gamete production between the sexes that result in increased mosaicism in the male germline.

[19] Resonant Recognition Modeling of the ataxin 1 protein has shown possible binding sites for growth factor independent transcription repressor 1 (Gfi-1).

The predictions of this computational model reveal an interaction that could play a role in SCA1 pathology, because the Gfi-1 protein is known to cause selective degradation of Purkinje cells.

It was historically believed to be caused by aggregation and deposition of the affected protein similar to other polyglutamine expansion diseases,[20] however rodent model studies have shown significantly later formation of nuclear inclusions of mutant proteins in cerebellum and spinal cord neurons than in cortical and hippocampal neurons, which typically show only mild degeneration in SCA1 persons, suggesting a more complicated mechanism.

However mice lacking both copies of ataxin 1 do not develop progressive neurological symptoms or show signs of atrophy, suggesting that toxicity of the mutated protein, not loss of function, is the main mechanism for SCA1 pathology.

[24] Mutant ataxin-1 also known to alter the neural circuitry of the developing cerebellum, which may lead to later vulnerability of Purkinje cells and suggests the existence of non-cell autonomous toxicity.

[27] Similarly, removal of the AXH domain from ataxin 1 prevents aberrant interactions with growth factor independent transcription repressor 1 that leads to GFI1 degradation in the proteasome.

This includes loss of dendritic aborization, or branching, early in disease progression and eventual atrophy of brain tissues in later stages.

[21] SCA1 causes moderate degradation of a variety of tissues, including both hemispheres of the cerebellum, the cerebellar vermis, the pons, and the brain stem.

[32] Central nervous system tissues, unlike that of bone, muscle, or skin, lacks mechanisms for endogenously generating and differentiating new cells and for restoring long distance patterns and connections as they are lost, so as degeneration progresses the losses are permanent.

Under physiological conditions, BG mediates the uptake of synaptic glutamate via the excitatory amino acid transporter (EAAT1, also known as GLAST and encoded by Slc1A3 gene), preventing excitotoxicity.

Excessive release of the S100β protein by Bergman glial cells affects synaptic transmission in Purkinje neurons, disrupting short-term plasticity.

[39] Genetic testing is the only definitive way to differentiate between spinocerebellar ataxia types because of the similarity between clinical characteristics of these diseases and the large variance between cases.

[43] Presymptomatic, prenatal, and preimplantation testing are typically requested through a genetic counsellor and require existing family history and documentation of informed consent of the consultand.

PAGE and CE both use timed cycles of electricity to draw pieces of DNA through a porous polymer, separating analytes by a combination of ionic mobility, size and mass.

[45] For repeat lengths within the range where interruptions are relevant, assays like CE and PAGE will not determine if the strain is pathogenic and additional testing will be required.

A cerebellar exam may include saying phrases with many consonants to detect scanning speech, detecting horizontal gaze nystagmus by following a finger with the eyes, performing rapid alternating movements like rotating a hand from palm to back repeatedly, testing the Holmes rebound phenomenon, and testing patellar reflex for hypotonia or hypertonia.

In this test, SCA1 typically has normal reflex latency, and does not consistently show a deficit in VOR function, distinguishing it from SCA3 and Friedreich's ataxia.

These studies suggest that multidomain physical therapy, more focused coordinative training, and exergaming routines all produced improvements in SARA scores equivalent to at least one year of normal progression, 2.2 points or more on average, over the course of several weeks.

[55] Overall, physical therapy for individuals with ataxia has modest evidence supporting its efficaciousness, but current practice uses custom treatments without a standard decision making procedure between clinics, which limits the ability to reproducibly assess the quality of routines in literature.

When swallowing problems become severe enough that aspiration pneumonias are frequent or dietary changes fail to prevent weight loss, a feeding tube may be considered.

[62] Prevalence of each type of SCA varies with geographic region and ethnicity, possibly because of founder effects and historic migration patterns.

[70] By the late 19th and early 20th centuries, extensive research into the characterization, cause, and diagnostics of hereditary cerebellar ataxias was underway with the work of several prominent neurologists, including Jean-Martin Charcot, Pierre Marie, Nikolaus Friedreich, Adolph Strümpell, and others.

In 1945, John Schut received free medical school education for his service with the United States Army during the second world war and began his own efforts researching hereditary ataxia.

Inhibitors of key proteins in this pathway may be used in combination therapy to potentially decrease expression and lower steady state concentrations of ataxin 1.

Studies using RNAi agents delivered by adeno associated viruses (AAV) has been shown to halt progression of disease and lead to some recovery of function with treatment applied to only the deep cerebellar nuclei in mice[83] and rhesus macaques.

SCA1 has also shown to be difficult to target reliably with single-nucleotide polymorphisms limiting the number of ways RNAi and antisense therapy techniques can be designed to treat SCA1.

[87] Similarly, the drug baclofen, which is used to help reduce spasticity in persons with multiple sclerosis and related diseases, operates as an agonist of γ-aminobutyric acid type B receptors (GABABR).

[16] While there is currently no known method for exclusively promoting polyglutamine contractions in vivo, techniques using programmable nucleases have shown some promise in causing these changes in vitro.

These techniques are of interest to researchers as a possible treatment for neurodegenerative diseases, but currently are of limited success in animal models, and in in-vitro cell culture studies.