Both of these techniques are difficult to apply to polyglutamine diseases because targeting the polyglutamine tract may cause normal genes to be downregulated as well. 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. Reducing toxicity and increasing cell survival
Because of the numerous interactions ataxin-1 has with other proteins, techniques for reducing toxicity of the mutant ataxin-1 protein often change the expression of related proteins. For example, ataxin-1-like has many common domains with ataxin-1 and overexpression of ataxin-1-like compete with ataxin-1 and prevent its integration into other complexes, reducing toxicity. This effect was replicated in mice models using AAVs, and shown to be about as effective as RNAi techniques at slowing the progression of symptoms. 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). This pathway crosstalks with the mGluR1 pathway, which interacts with the ataxin 1 protein and proteins responsible for localization and degradation of ataxin 1, suggesting that baclofen may be a viable treatment for SCA 1 treatment.Molecular chaperones are introduced proteins that may have interactions with the mutant protein that reduce toxicity by various mechanisms.
CE is advantageous over PAGE in that molecular weight measurements like mass spectrometry can be used with analytes, whereas PAGE requires the use of Southern blot to allow comparison to a sequencing ladder. 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. Clinical
No formal diagnostic criteria exist for most SCAs, and genetic testing is the only certain diagnostic method, but clinical examination of signs and symptoms may be vital to distinguishing SCAs from non-genetic ataxias, and from other types of genetic ataxias. Clinical examination can also help distinguish between SCA types to some extent, so genetic tests for certain types can be prioritized over others. Diagnosis of SCAs often begins with the detection of symptoms that suggest a cerebellar disorder, like progressive ataxia or dysarthria, or with recognition of similar symptoms to a case identified in the individuals family history, especially in first or second degree relatives. Many laboratory studies can be used to further narrow the potential cause of ataxia; imaging of brain and spinal cord and various electrophysiology exams may be useful for identifying disease phenotypes and blood and urine studies may rule out acquired causes. : 4 When evaluating ataxic disorders and their treatments, there are numerous tests that a neurologist may perform. Tests may be evaluated individually or follow a scale for evaluating the ataxia.