Current treatment pipelines involve the use of pharmacological molecules to target affected downstream pathways, as well as genetic therapies to decrease toxic polyQ gene products. The path to effective therapies for SCAs is hampered by their heterogeneity; specific therapeutic approaches may be required for each genotype.
SCAs are heterogeneous, 47 SCA subtypes have been identified, and the number of genes implicated in SCAs is continually increasing. Each subtype is named SCA followed by a number; the numbers are progressive and represent the chronological order in which the disease locus or causative gene of the subtype was identified. The research work is still in progress to find out more information. Out of the autosomal dominant ataxias, SCA3 is the most common worldwide, followed by SCA1, 2, 6, and 7.
Spinocerebellar Ataxia (SCA) treatment landscape is currently devoid of any approved therapies. The clinical care of patients with SCA focuses on managing the symptoms through physiotherapy, occupational therapy, and speech therapy.
Intense research has greatly expanded understanding of the pathobiology of many SCAs, revealing that they occur via interrelated mechanisms (including proteotoxicity, RNA toxicity, and ion channel dysfunction), and has led to the identification of new targets for treatment development.
In past decades, several pharmacological treatments were tested in clinical trials for their efficacy toward ataxia. Some encouraging results were reported in a few randomized, double-blind, placebo-controlled studies, with drugs, including riluzole, valproic acid, varenicline, and lithium carbonate, but no definite evidence of benefit was established.
Riluzole, a drug licensed for the treatment of ALS, was reconsidered for the treatment of patients with ataxia owing to its ability to inhibit presynaptic glutamate release and to activate calcium-activated potassium channels. The anticonvulsant valproic acid has been proposed as a pharmacological treatment in SCA3/MJD for its neuroprotective properties as a pan-histone deacetylase inhibitor.
There exists a large number of FDA-approved drugs which have been tested in randomized, double-blind, placebo-controlled trials in individuals with SCA but none has resulted in approval for treatment of SCAs by the FDA or the EMA.
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