Machado Joseph disease: clinical and genetic aspects, and current treatment

作者：Morales Saute Jonas Alex; Jardim Laura Bannach^*

来源：Expert Opinion on Orphan Drugs, 2015, 3(5): 517-535.

DOI：10.1517/21678707.2015.1025747

• ataxin-3
• disease-modifying treatment
• Machado-Joseph disease
• polyglutamine disorders
• pre-implantation diagnosis
• spinocerebellar ataxia type 3
• symptomatic treatment

Introduction: Spinocerebellar ataxia (SCA) type 3/Machado-Joseph disease (SCA3/MJD) is the most common SCA worldwide. SCA3/MJD is an adult onset cerebellar ataxia associated with pyramidal, lower motor neuron and extrapyramidal findings, resulting in heterogeneous phenotypic presentations. SCA3/MJD is caused by a CAG repeat expansion at the ATXN3 gene that codes for ataxin-3. Mutant ataxin-3 trigger multiple, interconnected pathogenic cascades, but many of key disease mechanisms remain unclear.
Areas covered: This review focused on the present knowledge about the genetic characteristics, ancestral origins, selective forces, clinical course and determinants of phenotypic heterogeneity of SCA3/MJD. Disease-modifying and symptomatic therapies were also detailed.
Expert opinion: Although no evidence exists for disease-modifying therapies for SCA3/MJD, symptomatic treatments for some disease signs are available. Genetic counseling is fundamental and should include discussion on options such as prenatal or pre-implantation diagnoses, and adoption, as ways to prevent the disease. Basic and translational science trying to speed the exchange of novel therapies (e.g., gene silencing) to the clinics will be central to the development of effective therapies, together with consortiums to define surrogate disease biomarkers and essential data for planning future clinical trials on SCA3/MJD.

• 出版日期2015-5