Treatment and management issues in ataxic diseases

A homozygous mutation ofVWA3Bcauses cerebellar ataxia with intellectual disability

“…Considering the clinical features and neuroimaging findings, cerebellar ataxia in the family is due to neurodegeneration or late-onset neurodevelopmental abnormality. These clinical features might be indistinguishable from those in cerebellar ataxia associated with chronic vitamin B 12 and E deficiencies, and low thyroid levels due to autoimmune thyroiditis 34. Potential differential diagnoses for late onset recessive ataxias include Friedreich's ataxia,23 ataxia telangiectasia,35 autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS),36 SYNE1- ARCA type 1 (ARCA1),37 and ataxia with ataxia-oculomotor apraxia type 1 (AOA1)38 and type 2 (AOA2) 39.…”

A 40‐year‐old woman with difficulty going down stairs in high‐heeled shoes

“…24 Therapeutic approaches using RNA interferencebased gene silencing are currently under investigation in SCA7 patient-derived fibroblasts. 30 Better understanding of the phenomenology of SCA7 will help translate genetic and molecular insights into meaningful treatments. 27 With further understanding of the pathobiology of SCA7, perhaps by using patient fibroblast-derived neural stem cells and yeast models of the molecular cascade to enable high-throughput screening of candidate compounds, 28,29 it may be possible to develop interventions to prevent or arrest the gene signaling that leads to misfolded proteins that damage and destroy neurons.…”

“…In the interim, clinicians are exhausting the available symptom-based therapies in an attempt to treat SCA7's many manifestations. 30 Better understanding of the phenomenology of SCA7 will help translate genetic and molecular insights into meaningful treatments. In this family, we determined that ERG is a useful biomarker of the transition to the symptomatic stage.…”

Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation

“…Currently, no therapy is known for SCA6, except for the use of Acetazolamide, a brain carbonic anhydrase inhibitor, that has been successfully used for EA2 but is possibly effective only in the episodic phase of SCA6 (Jen et al, 1998 ); however, Yabe et al ( 2001 ) suggested that this drug can also temporarily reduce the severity of symptoms during the progression of the disease. Other therapies are in the experimental phase or their use is still controversial (Perlman, 2012 ) such as the NMDA antagonist (Ogawa et al, 2003 ; Ogawa, 2004 ) and branched-chain amino acids (BCAA), which improve neurotransmission among cerebellar neurons by stimulating intracellular glutamate metabolism (Mori et al, 2002 ). The latter treatment, used for other polyglutamine disorders, is likely to act on the effects of CAG repeat toxicity, in a later phase of the disease.…”