Current concepts in the treatment of hereditary ataxias

Abstract

Hereditary ataxias (HA) represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

Neurorehabilitation therapy in spinocerebellar ataxia type 2: A 24‐week, rater‐blinded, randomized, controlled trial

“…Although SCA2–as with other SCAs–has been studied extensively, it is still considered an “orphaned treatment” disease, where a cure has not been found . Nevertheless, a promising gene therapy based on antisense oligonucleotide approach was significantly efficient in mouse models, and symptomatic therapeutical options are already available for humans …”

‘Staying strong on the inside and outside’ to keep walking and moving around: Perspectives from Aboriginal people with Machado Joseph Disease and their families from the Groote Eylandt Archipelago, Australia

“…Participants described how the family is continually living with the impact of MJD over the generations, similar to the experience of those with other hereditary neurodegenerative diseases [ 28 ]. Yet, rehabilitation services for this population have typically focused on the individual, rather than families, and commence after onset of symptoms [ 29 – 31 ] when adjusting to life with the disease may be the only alternative [ 28 , 32 , 33 ]. The experience of MJD described in this study aligns closely with the biopsychosocial Family System Genetic Illness (FSGI) model [ 34 ], which recognises the ongoing impact on individuals and families along the life cycle and phases of genetic disease [ 35 , 36 ].…”

Postural Tremor and Ataxia Progression in Spinocerebellar Ataxias

“…However, these types of tremor were uncommon among SCAs, except for ataxia with vitamin E deficiency, which is often associated with head tremor. 55 Finally, we only focused on the repeat expansion in selected ataxia genes in the genetic modifier analyses. Variants in other ataxia genes, along with expansions of the FMR1 gene, might also play a role, which requires further exploration.…”