Spinocerebellar Ataxias

The purpose of this expanded access protocol is to provide access to the investigational drug troriluzole in patients with spinocerebellar ataxia (SCA).

Spinocerebellar ataxia (SCA) is a type of autosomal dominant ataxia and there is currently no effective treatment. The goal of this clinical trial is to learn the efficacy of navigated iTBS (Intermittent theta-burst stimulation) targeting the cerebellum to treat hereditary spinocerebellar ataxias in adults and explore the role and neural plasticity mechanisms. It will also learn about the safety of cerebellar transcranial magnetic stimulation. The main questions it aims to answer are: 1. Does navigated iTBS targeting the cerebellum improve the symptoms and clinical scale score of ataxias? 2. Safety evaluation measures included treatment-related dizziness, head and neck pain, tinnitus, hearing loss, and epilepsy. Adverse reactions were reported by both subjects and investigators. Participants will: 1. Navigated iTBS targeting the cerebellum or sham stimulation every day for 7 day, 2. Assessments were made at baseline, within 24 hours after the end of treatment, after 12 weeks, and after 24 weeks of telephone follow-up.

Effective walking and balance require not only lower limb muscle strength but also coordinated movement. For individuals with Spinocerebellar Ataxia (SCA), rehabilitation strategies targeting coordination are essential to improving mobility and reducing the burden on caregivers. However, evidence-based rehabilitation approaches for ataxia remain limited. Recent studies suggest that improvements in motor learning are often accompanied by changes in cortical excitability. Abnormal cortical excitability in SCA patients may hinder rehabilitation efforts, yet priming strategies-such as exercise or specific stimuli-have been shown to enhance motor learning by modulating cortical excitability. Cycling exercise, in particular, has demonstrated the potential to improve coordination and influence cortical plasticity in individuals with SCA, making it a promising priming strategy for coordination training. This clinical trial aims to: 1. Investigate the priming effect and neural mechanisms of acute cycling exercise on coordination training in patients with SCA. 2. Explore the long-term impact of priming cycling training on cortical plasticity and functional mobility in individuals with SCA. This study seeks to provide insights into optimized rehabilitation interventions that could enhance the quality of life and independence for people with SCA.

The purpose of the clinical trial is to study the therapeutic efficacy and safety of Stemchymal® infusions for polyglutamine spinocerebellar ataxia treatment by a randomized, double-blind, placebo-controlled study design. Eligible subjects will receive Stemchymal® through intravenous infusion.

Inherited movement disorders are rare conditions, whose cumulative prevalence are in the order of 5-10/100,000 inhabitants, in most cases progressive and can lead to a significant loss of autonomy after one or more decades of evolution. They include spinocerebellar ataxias and hyperkinetic disorders (dystonias, choreas, tremor, parkinsonism and myoclonus with variable combination of those, or more complex alteration of movements). The existence of the National Reference Centre (CMR) for Rare Diseases (CMR Neurogenetics, devoted to ataxias and spastic paraparesis, dystonia and rare movement disorders and CMR Huntington, devoted to Huntington Disease) has allowed a more integrated vision of these diseases. This is illustrated, in the same family, by the occurrence of different clinical expressions of spinocerebellar ataxias and hyperkinetic disorders that share the same genetic background. Conversely, different causal mutations within the same gene may have very different ages at onset and a wide range of clinical expression, and the spectrum of new phenotypes linked to a single gene is still expanding . Many ataxia and dystonia genes are involved in similar pathways. There are numerous arguments supporting a share pathogenesis including synaptic transmission and neurodevelopment . BIOMOV project aims to : 1. establish the clinical spectrum and natural history of these diseases, 2. understand the role of genetic and familial factors on the phenotype, 3. elucidate the molecular basis of these disorders and evaluate diagnostic strategies involving molecular tools for clinical and genetic management, 4. develop multimodal biomarkers both for physiopathological studies and for accurate measures of disease progression, 5. develop trial ready cohorts of well characterized genetic patients, 6. test new therapies either symptomatic or based on pathophysiological mechanisms.