Stratifying SCA3 patients towards individualized treatment

- Genotype and characterize genetic variances within SCA3 patients in order to
a) stratify patients for known modifying factors, and
b) identify novel important variances

Spinocerebellar Ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) is caused by a CAG repeat expansion within the ATXN3 gene. The ATXN3 gene contains non­synonymous single nucleotide polymorphisms (SNP) within its coding region which cause amino acid changes or even a premature stop in the encoded ataxin-3 protein. The ATXN3 gene is further subjected to alternative splicing and ataxin-3 isoforms affect not only major aspects of ataxin-3 function but also main disease mecha­nisms and SCA3 pathogenesis. Moreover, genetic modifiers are known to influence the disease onset and progression in SCA3 patients and, importantly, may impact both gene therapy and target-specific treatment approaches. Therefore, genetics modifiers and the haplotype status of SCA3 patients (both of the normal and the expanded allele) need to be considered when planning, conducting and evaluating clinical trials.

Cohorts used SCA3
Funding available? Available for proof of principle, to be sought for larger project
Trial readiness category 2: setting the stage for trial readiness (general cohorts, outcome measures or treatment approach identification)

Contact person:
Thorsten Schmidt
Institute of Medical Genetics & Applied Genomics, University of Tübingen, Tübingen, Germany
Center for Rare Diseases (ZSE Tübingen), Tübingen, Germany

Further project partners:
Mario R. Cornejo-Olivas
Instituto Nacional de Ciencias Neurológicas, Lima, Peru
Marcondes C. França Jr
Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
Carlos R. Gordon
Tel Aviv University, Tel Aviv, Israel
Laura Bannach Jardim
Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
Maria Luiza Saraiva Pereira
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil