frenkel exercises, which was developed by heinrich frenkel in the mid nineteenth century; these exercises were drawn from contemporary physical medicine and rehabilitation techniques, called medical gymnastics, and from everyday activities, like standing up from a chair, to find exercises which are closely related to the pathology of ataxia and rely on slow practice and on the individuals perseverance to relearn key motor skills, replacing lost proprioception with visual feedback. there are exercises for lower limbs, like extending the legs, and upper limbs, like placing pegs in boards, and depending on the severity of the ataxia can be performed laying down, sitting, or standing up. all exercises often start with simple movements and become progressively more difficult to emulate real world movements affected by the disorder. common recommendations for persons with dysphagia, or swallowing problems, include pureeing food, replacing difficult to eat foods in the diet, or changing posture during eating. 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.: 82–86 typically these are percutaneous endoscopic gastrostomy jejunal tubes (peg-js), however these do not necessarily lead to a decreased incidence of aspiration, as clogs may result in gastroesphageal reflux which can be aspirated. direct peg-js seem to cause less frequent reflux and have lower incidence of aspiration pneumonia compared to the standard peg-j procedure. numerous strategies for treating dysphagia have been investigated including physical exercises like modified valsalva maneuvers, pharmaceutical treatments focused on treating spasticity, and compensatory practices including adjusting posture and longer chewing. these strategies, like the treatment of many symptoms hereditary ataxias, have small scale evidence for their usefulness but are not yet established by large studies. as with all hereditary diseases, concerns about the impact on family members, especially children, are often very important. individuals diagnosed with sca 1 may seek genetic counseling to aid in family planning, developing coping skills, and planning for the future. persons with sca 1 may consider in vitro fertilization with preimplantation testing to prevent passing the disease on to their children. prognosis penetrance for sca1 is 100% for most alleles, so almost all individuals who have at least one copy of the mutated gene will eventually develop symptoms. at least one case has been reported where penetrance may have been incomplete in a woman with 44 glutamine repeats with histidine interruptions whose father had exhibited symptoms, but herself had not shown symptoms at the age of 66. individuals with a low number of repeats, around 39 to 55, typically live past reproductive age and can pass on the disease to their children, while high repeats may express juvenile onset and fatality. epidemiology the national institute of health reports that sca1 has a prevalence of approximately 1 or 2 per 100,000 however a review of literature has shown that these estimates vary significantly from study to study and can be less than 1 per 100,000 or as high as 6 per 100,000. among all types of sca, sca1 is among the most common and the portion accounted for by sca1 varies between geographic regions, with percentages as high as 40% of all sca diagnoses in populations in russia and south africa being sca1. in the united states sca1 accounts for 6% of sca diagnoses. overall, sca1 accounts for 6-27% of all cases dominant ataxias.: 6 because of its late onset, often appearing after reproductive age, sca1 exerts low selection intensity, ranking about 0.19 on the crow's index, but intensity may vary with time within a population or family, as anticipation increases the number of cag repeats. one implication of this is that sca1 is unlikely to disappear from a population by natural selection alone. prevalence of each type of sca varies with geographic region and ethnicity, possibly because of founder effects and historic migration patterns. high prevalence regions include central poland, where 68% of autosomal dominant cerebellar disorders are sca1; communities in tamil nadu, where up to 7.2% of the population has sca1 in some small villages; the tohoku region on the northern portion of honshu island, with 24.8% of cases being sca1; and among yakut populations in eastern siberia, with a prevalence 46 per 100,000 in rural populations. history ataxia as a symptom was first described by french neurologist duchenne de boulogne in a subject with tabes dorsalis. 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. marie described a number of cases of hereditary, adult onset disease he thought to be clinically distinct from friedreich's ataxia, spastic paraplegia, and other known types of ataxia, calling the syndrome hereditary cerebellar ataxia, though it became known marie's ataxia. while the hereditary patterns were clearly distinct, there was on-going debate well into the 1940s over whether marie's ataxia was really distinct from freidreich's ataxia and strümpell's paraplegia and if these category's themselves represented a single disease or many. this was because of the heterogenous nature of hereditary ataxias, the similarity of symptoms, and the lack of understood biochemical mechanisms. further frustration with the ambiguity of terms introduced by marie and friedreich resulted in the creation of other systems to classify ataxias. gordon morgan holmes and godwin greenfield each developed systems of categorizing ataxias, giving rise to categories called olivopontocerebellar atrophy and spinocerebellar degradation, though little consensus between the systems was achieved, and many terms are used interchangeably. in the depression era united states, the schut family in minnesota was one family known to carry a hereditary ataxia. several members of the family actively participated in research and the family consented to post mortem examinations of the brains of several deceased relatives. the disease in the schut family was found to have an autosomal dominant inheritance pattern, and afflicted the spinocerebellar tract. 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.: 90–91 schut developed ataxia like many of his relatives. in 1957, when schut's ataxia progressed to a point where he was unable to continue work in regular medical practice, he founded the national ataxia foundation with lab space donated by glenwood hills hospital in minneapolis.: 131 john schut's nephew, lawerence schut, also became an ataxia researcher and contributed to localizing a spinocerebellar ataxia gene to the human leukocyte antigen complex in chromosome 6. the success in linking one of these class of diseases to a locus showed that the classification systems in use were unable to distinguish between diseases with many different causes. many ataxic disorders which were historically identified as marie's ataxia, olivopontocerebellar atrophy or other names were now reclassified as types of spinocerebellar ataxia, each type numbered in order as a new locus was found. in 1993, the gene and a mutation causing spinocerebellar ataxia type 1 was identified. it was the first genetic defect found known to cause an ataxic disorder. research directions treatment and mitigation of neurodegenerative disorders is of particular interest to researchers, and several potential options for sca1 are under investigation. as the pathology of sca1 is complex, there are several possible approaches to treatment, which include clearance of expanded ataxin 1 proteins, reducing the toxicity of expanded ataxin 1 proteins, suppressing production of ataxin 1, multiple gene therapies, and replacing lost brain cells. because many scas, including sca1, are polyglutamine diseases and operate by similar mechanisms to huntington's disease many promising treatments for huntington's disease are being investigated for scas as well. gene downregulation and silencing because spinocerebellar ataxias are often linked to a mutation on a single gene, modifying how the gene is expressed can modify the phenotype. there are several approaches to modifying the expression of mutant proteins, including techniques that completely stop expression, known as gene silencing. in sca1, pathogenesis requires constant expression of the mutant atxn1 gene, and silencing has been shown to halt further progression of the disease, clear nuclear inclusions and aggregates and lead to partial recovery of motor functions in rodent models with conditional expression of the gene. the conditional expression of atxn1 in mice models differs from how the gene would be silenced therapeutically but the results indicate that therapeutic methods of gene silencing may be viable for treatment and management of sca1. the process that turns coded information in dna into proteins requires two steps: transcription, in which dna is used to generate a complementary rna strand by rna polymerase, and translation, in which rna is used to produce a protein by ribosomes. disrupting either step can slow or prevent the expression of a mutant gene. ataxin 1 is involved in a number of signaling pathways and its expression is controlled by signaling pathways. the mapk/erk pathway has been shown to activate ataxin 1 expression, and msk1 also phosphorylates ataxin 1, controlling its localization and degradation. 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. one technique for disrupting translation, antisense oligonucleotide therapy, which uses single strands of rna complementary to the target to prevent the target from binding to a ribosome and trigger the degradation of the target, has already begun clinical trials in other neurodegenerative disorders with many different delivery mechanisms. a similar technique is rna interference or rnai. instead of complementary 'antisense' strands of rna, rnai uses very small double stranded segments of rna called small interfering rna which triggers degradation of the target before it can be translated. 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 and rhesus macaques. 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. studies in both mice models and drosophila models have shown that heat shock proteins 40 and 70 may reduce toxicity of expanded ataxin 1 proteins and slow progression of sca1. 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. programmable nucleases are proteins that can break dna strands near sequences that can be specified by scientists before use. this includes crispr/cas9, which uses a protein found in bacteria and guide strand of rna, and zinc finger nucleases, which use engineered proteins with special recurring dna binding domains to guide an attached nuclease. a study reports that both crispr and zinc fingers nucleases that rely on double strand breaks trigger contractions and expansions with nearly equal frequency, while crispr using a mutant variation of cas9, cas9 d10a or cas9 nickase, which causes only single strand breaks, produced mainly contractions. in mice, mitochondrial impairments contribute to sca1 progression. prominent alterations in purkinje cell mitochondrial proteins coincide with the symptomatic phase of the