Treatment and Management of Autosomal Recessive Cerebellar Ataxias: Current Advances and Future Perspectives

The autosomal recessive cerebellar ataxias (ARCAs) compose a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by prominent cerebellar ataxia, dysmetria, dysarthria, and nystagmus that are inherited in an autosomal recessive fashion. The diagnosis of ARCAs is challenging because of their low prevalence, poor medical recognition, and heterogeneous clinical presentation with many overlapping features between entities. There currently exist no disease-modifying therapies for most ARCAs, and treatment is mainly symptomatic, aimed at prolonging independence and maintaining the quality of life. As knowledge of the common pathogenic pathways underlying several ARCAs grows, so do these pathways to target with new drugs. Chelation or enzyme replacement therapies are available for some specific ataxias caused by amenable metabolic alterations. A large number of drug trials are ongoing and aim to identify new therapeutic approaches to expand the options in our repertoire. Improved protocols of motor rehabilitation and noninvasive cerebellar stimulation have been shown to delay disease progression and maintain quality of life. Furthermore, recent progress in gene and molecular targeting therapies is rapidly expanding and holds promise for repairing defective genes. Neurotransplantation of grafted stem cells, which is still at the experimental preclinical stage, has opened new therapeutic strategies aimed at delaying cell degeneration and facilitating compensatory functions. This article is an overview of the current management and treatment strategies with an emphasis on promising perspectives for patients with ARCAs.

Automated summary

Autosomal recessive cerebellar ataxias (ARCAs) are a group of neurodegenerative diseases characterized by cerebellar ataxia, dysmetria, dysarthria, and nystagmus that are inherited in an autosomal recessive fashion. The diagnosis of ARCAs is challenging due to low prevalence and overlapping clinical features. Treatment is mainly symptomatic, but new therapeutic approaches are being explored. Improved motor rehabilitation protocols and noninvasive cerebellar stimulation can delay disease progression, and gene and molecular targeting therapies show promise for repairing defective genes. This article provides an overview of current management and treatment strategies for ARCAs, with an emphasis on promising perspectives.