Cerebellar Ataxias, Spastic Paraplegias
Conditions
Keywords
Cerebellar ataxias, Spastic paraplegias, Mutations spectrum, Linkage studies, Genetic counselling
Brief summary
Cerebellar ataxias (CA) and spastic paraplegias (SP) are genetically and clinically very heterogeneous. More than 40 loci are already known but the number of phenotypes is even greater suggesting further genetic heterogeneity. These progressive disorders are often severe and fatal, due to the absence of specific therapy. The SPATAX network combines the experience of European clinicians and scientists working on these groups of diseases. Over the past year, they have assembled the largest collection of families and achieved a number of tasks (initiation of a clinical and genetic database, distribution of DNA to participating laboratories, mapping of three new loci, and refinement of several loci). In addition to clinicians from Europe and Mediterranean countries, who play a major role in collecting families according to evaluation tools developed and validated by the SPATAX members, the group includes major European laboratories devoted to the elucidation of the molecular basis of these disorders. Each laboratory will centralize all families with a subtype of autosomal recessive (AR) CA (n=116) or SP (n=207) in order to efficiently map and identify the responsible gene(s). Genome-wide scans are already underway in 61 families. Given the expertise of the participants, the researchers expect to map and identify several genes during the course of this project. The spectrum of mutations and phenotype/genotype correlations will be analysed thanks to this unique series of patients with various phenotypes. The knowledge gained will be immediately applicable to patients in terms of improved positive diagnosis, follow-up and appropriate genetic counselling. In the long term, models for genetic entity will be developed in order to understand the pathophysiology and to identify new targets for treatment. The series of patients assembled and the precise knowledge of natural history will facilitate the implantation of therapeutic trials based on rational approaches.
Interventions
None listed
Sponsors
Institut des Maladies Rares
National Research Agency, France
Paris Brain Institute (ICM)
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
FAMILY_BASED
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Progressive ataxia or paraplegia
Exclusion criteria
* Lack of signed informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize clinically the different forms of these diseases | Year 1 to Year 7 | Validation of a new quantitative tool with more sensitive grading scale of cerebellar syndrome, spasticity and their consequences. In one single device, three tests were assessed for hand coordination ( tapping test , peg board test and click test ), one test for dysarthria and a final test to quantify walking disorders due to spasticity (distance covered in 5 seconds). |
| Elucidate the molecular bases of these diseases | through study duration (through study duration (up to 14 years) ) | To elucidate the molecular bases of these diseases (identify the loci/genes involved as well as those that modulate their expression) in order to enable the development of molecular diagnostics, the study of disease mechanisms, the identification of biomarkers and, subsequently, to propose new treatments. |
| Establish the natural history of spino-cerebellar degeneration | Year 1 to Year 7 | Investigators intended to follow the clinical status of this cohort of patients for 7 years, by assessing the progression of the pathology each year with a neurological exam |
Countries
Algeria, Belgium, Denmark, France, Israel, Italy, Lebanon, Morocco, Netherlands, Norway, Portugal, Saudi Arabia, Serbia, Tunisia, United Kingdom
Outcome results
None listed