Clinical Research Directory

Investigating the Genetic and Phenotypic Presentation of Ataxia and Nucleotide Repeat Diseases

The purpose of this study is to create a repository for cerebellar ataxia and nucleotide repeat diseases in order to fully investigate the genetic and phenotypic presentations of both.

Real-World Data Study of Troriluzole-Treated Patients With Spinocerebellar Ataxia (SCA) Compared to a Matched Natural History Control

The purpose of this study is to leverage two sources of real-world data (RWD) to assess the effectiveness of troriluzole after three years of treatment in patients with SCA by comparison to an external control of untreated patients who were followed in a natural history cohort. Real world evidence of effectiveness will be assessed from the RWD sources to examine the treatment effects of toriluzole in SCA out to 3 years. Progression rates of SCA differ by genotype and long-term follow-up is needed to assess for potential efficacy in this rare disease.

Troriluzole in Adult Participants With Spinocerebellar Ataxia

The purpose of this study is to compare the efficacy of Troriluzole (200 mg once daily) versus placebo after 48 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

Use of a New Smartphone Application to Determine Changes in Eyeblink Conditioning From Home Training in Individuals With Spinocerebellar Ataxia

Spinocerebellar ataxias are a group of disorders that cause severe disability and can be fatal. There are currently no known disease-modifying treatments available for use, and there is a critical need to find treatments that slow disease progression and allow affected individuals to live more functional lives. Aerobic training show promise as a treatment for these diseases, but it is unclear if training induces neuroplastic changes within the damaged cerebellum to enhance motor learning, or if improvements are primarily caused by changes in leg strength, fatigue, and endurance. It is crucial to understand how the training impacts the brain, and particularly the cerebellum, in order to determine the most effective training regimen. To examine the impact of aerobic exercise on the brain, this study proposes using eyeblink conditioning, a form of motor learning that is dependent on the cerebellum. This study will utilize BlinkLab, a newly developed smartphone application, that overcomes the typical barriers of testing eyeblink conditioning by allowing in-home assessments without the need for expensive equipment. The investigators hypothesize that: 1) individuals with spinocerebellar ataxia will have impaired eyeblink conditioning, and 2) aerobic exercise, but not balance training, will improve eyeblink conditioning in this population. If these hypotheses are found to be true, it would further support that aerobic exercise is able to enhance motor learning in individuals with cerebellar damage. In Aim 1, investigators will test eyeblink conditioning in individuals with ataxias and follow them over time to see if eyeblink conditioning might be a biomarker for cerebellar ataxia disease progression. The investigators will then use these preliminary results to devise a larger study to further validate eyeblink conditioning as a biomarker for ataxia disease progression. Aim 2 will determine the impact of training on eyeblink conditioning. The investigators expect that aerobic training, but not balance training, will enhance eyeblink conditioning in spinocerebellar ataxia. Finally, Aim 3 will explore the use of eyeblink conditioning as a biomarker of neuroplasticity.

Efficacy of Cerebellar Transcranial Magnetic Stimulation to Treat Hereditary Spinocerebellar Ataxias

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.

Cycling-Based Priming Coordination Training for Enhancing Ataxia Recovery and Brain Plasticity

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.

Open Pilot Trial of BHV-4157

24 adults, between the ages of 18 and 75 years, with cerebellar ataxia will be enrolled in a 12 week trial of BHV-4157 for treatment of ataxia. BHV-4157 is a pro-drug of riluzole (which is currently FDA-approved for ALS, Lou Gehrig's disease). There will be 5 visits to UCLA required--Screening when general and neurological examination, blood and urine testing, ECG, and questionnaires will be administered; Baseline when general and neurological examination and questionnaires will be administered and study drug dispensed; Week 4 and Week 12 when general and neurological examination, blood and urine testing, ECG, and questionnaires will be administered; 2 weeks after finishing study drug when general examination and blood testing will be completed. There is an option for a 36 week extension of the study drug trial.

Stemchymal® for Polyglutamine Spinocerebellar Ataxia

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.

Biomarker Research in Inherited Movement Disorders

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.