Active clinical trials for "Spinocerebellar Degenerations"

This is a piloting study using continuous motor training provided via whole body-controlled video games (exergames) to establish proof-of-concept evidence that such training leads to motor and neural changes in pre-manifest subjects with spinocerebellar ataxias (SCA).

The objectives of this study are: To validate the inter-rater and intra-rater reliability of a new scale for the assessment of ataxia and neurologic dysfunction (STAND) To assess common constructs and correlation between STAND subscale items.

Congenital ataxias (CA) are rare, non progressive diseases, characterized by psychomotor retardation, hypotonia followed by ataxia. The presence of the "molar tooth" on MRI allowed to define Joubert syndrome, a peculiar form of CA. Apart from this group, CA are mostly associated with cerebellar atrophy or hypoplasia without molar tooth on MRI. CA are a clinically as well as genetically heterogeneous group of diseases. Early-onset ataxias are progressive but may be difficult to distinguish from CA in the first years of the disease. To date, few genes responsible for CA have been identified: ABC7 (X-linked CA associated with sideroblastic anemia), SLC9A6 (X-linked CA associated with severe mental retardation, autism and epilepsy), GPR56 (CA associated with polymicrogyria), ATCAY (pure CA in Cayman isolate); the involvement of the ATCAY and ABC7 genes has never been assessed in a large cohort of CA patients. Primary objective: To assess the frequency of mutations of the ATCAY and ABC7 genes in patients affected with non Joubert congenital or early-onset ataxia. Secondary objective: To identify new loci and/or genes responsible for CA To further describe the clinical phenotype of the CA and to assess the frequency of the various clinical types (pure CA/CA associated with spasticity/ syndromic CA, congenital/early-onset CA, sporadic/familial CA). To describe the clinical phenotype of CA related to mutations in one of analysed genes.

OBJECTIVES: I. Clinically evaluate members from families with a dominantly inherited ataxia and collect blood, skin and muscle samples for detailed molecular studies. II. Perform detailed clinical evaluations on patients with recessively inherited ataxias.

The autosomal dominant spinocerebellar degenerations are a highly heterogeneous, clinically and genetically, group of rare diseases and of severe evolution. So far, the responsible genes for less than 50% of the cases are known and because of their rarity, there are no phenotype-genotype correlations and well-defined disease history. The aims of the project are to develop and validate quantitative tools of the cerebellar syndrome and of the spasticity, to establish links between the phenotype and the result of the molecular analysis, to identify new loci/genes responsible for these disorders, and to establish the natural history of the disease according to the genotype. To this end, a prospective and multicentric study is proposed for recruiting and evaluating, clinically, a cohort of 225 patients; 150 of them are already followed-up in the centers involved. A DNA collection will be set up in order to search for the implication of new loci and genes. A clinico-genetic database will be set up combining data from successive clinical evaluations and those of genotyping. This strategy will allow access to genetic counselling and molecular diagnosis (positive, presymptomatic or prenatal diagnoses), based on a rational strategy from phenotype-genotype correlations and the information concerning the relative frequency of the genes. The detailed description, with the help of new evaluation tools and of the follow-up of the natural history of the disease according to the genotype, constitutes a crucial step in the design of therapeutical trials in these orphan disorders. Furthermore, the regular follow-up by specialized centers will allow better care of the patients.

The study will consist of a prospective observation of subjects in a natural history design. The investigators will monitor changes of clinical scales, quality of life, messenger ribonucleic acid (mRNA) of candidate genes (CCL11, TNFSF14, FCGR3B, CLC, and SLA) (and their peptide products, when possible), and eotaxin and S100B serum levels, in order to determine which of them is (are) the most sensitive. Participants will be stratified in three groups: ataxic carriers, pre-ataxic carriers and non-carriers (controls).

The study will consist of a prospective observation of subjects in a natural history design. Disease progression will be monitored through clinical scales and video-oculography. Participants will be stratified in three groups: ataxic carriers, pre-ataxic carriers and non-carriers (controls). The following clinical scales will be applied in all subjects at baseline and at months 12 and 24: SARA, SCAFI, CCFS, NESSCA, INAS and ICARS. Oculomotor function will be registered using video-oculography (EyeSeeCam, InterAcoustics) at the same time points. Progression rates, effect sizes and responsiveness to change will be established for all parameters and results will be compared between candidate biomarkers.

The general purpose of this observational study is to examine biomarkers associated with the pathology of neurodegenerative diseases to potentially develop novel therapeutic approaches.

This is an expanded access program to provide troriuzole for treatment of spinocerebellar ataxia.

This research investigates how cognitive-affective aspects evolve during the course of SCA3/MJD. Due to COVID-19 pandemics, this study protocol was adapted for online-only consultations. Evaluations happening after March 2020 have been done by videocall with patients, and no neurological evaluation was thus performed on these patients. A scale on Activities of Daily Living was added to the online protocol to replace SARA, SCAFI and CCFS scales.