Chorea

Researchers are conducting a first-in-human, multi-center clinical trial to study the effects of SRP-1005 in people with Huntington's disease (HD). The trial is designed to evaluate the safety and impact of SRP-1005, a drug given by subcutaneous injection, compared to a placebo. The study includes adult participants aged 21 to 70 years who have a genetically confirmed diagnosis of HD and are at specific disease stages. Participants will be randomly assigned to one of four groups receiving different doses of SRP-1005 or a placebo. The study is double-blind, meaning neither the participants nor the researchers know who receives the drug or placebo. The treatment period includes dose escalation and monitoring to assess the drug's presence in plasma, urine, and cerebrospinal fluid over several weeks. During the study, participants will be monitored for side effects and adverse events from baseline through 24 weeks. Researchers will collect blood, urine, and cerebrospinal fluid samples to measure drug levels and safety. Participants must agree to use effective contraception if applicable, and the study excludes those with certain infections, other neurological illnesses, or conditions that prevent safe lumbar puncture or MRI. The total participation lasts at least 24 weeks with ongoing safety assessments.

Researchers are developing a multicenter registry to collect and share data on pediatric patients who have undergone deep brain stimulation (DBS) for movement disorders such as dystonia, epilepsy, Tourette syndrome, and mood disorders. The study aims to improve understanding of DBS safety and effectiveness in children, as current data are limited and individual centers often have too few cases for strong research. This registry will support large-scale analyses and help refine DBS as a treatment option for hyperkinetic movement disorders in the pediatric population. The study involves gathering both retrospective and prospective clinical data from multiple pediatric centers. The registry will collect information on surgical techniques, patient outcomes, implant sites, and long-term effects of DBS. This collaborative data-sharing approach enables comprehensive evaluation of which patients benefit most from DBS and how it impacts their quality of life over time. Participants include children aged 0 to 18 years who have already received or are scheduled to receive DBS for neurological movement disorders. Data will be collected over five years to monitor safety, efficacy, and quality of life outcomes. The study does not involve treatment administration but focuses on gathering and analyzing clinical information. Parental or legal guardian consent is required for prospective participation.

Researchers are monitoring people with advanced idiopathic Parkinson's Disease who have moderate to severe motor symptoms that do not respond well to medication. This study is an international, observational registry following patients who have undergone a unilateral pallidotomy using the Exablate Neuro device. The goal is to collect long-term information about this treatment after its approval. The treatment involves a focused ultrasound procedure called unilateral pallidotomy performed with the Exablate Model 4000 system. This registry will observe patients who have already received this procedure as part of their standard care. No additional treatment is given as part of the study. Patients will be followed with visits at 3, 6, and 12 months after the procedure, and then annually for up to 5 years. During the follow-up visits, researchers will collect information including any side effects, medication use, motor function scores, dyskinesia severity, quality of life, work productivity, and overall impressions from both doctors and patients. Safety and effectiveness will be assessed mainly by tracking responder outcomes over five years. Participants will be closely monitored throughout the study period, which may last up to five years from the time of the procedure.

Researchers are conducting a phase II randomized placebo-controlled trial to study oral N-Acetylcysteine (NAC) in individuals who carry the Huntington disease gene but do not yet show clear motor symptoms. The study aims to assess clinical and brain imaging outcomes over a three-year period, focusing on slowing disease progression in this premanifest stage. Participants will be randomly assigned to take either 1 gram of NAC capsules or matching placebo capsules twice daily by mouth. The study is quadruple-masked, meaning that participants, caregivers, investigators, and outcome assessors do not know which treatment is assigned. The treatment period lasts up to three years, with ongoing monitoring throughout. During the study, participants will undergo regular brain MRI scans to measure caudate atrophy rate and be evaluated for motor changes indicating disease progression. Various cognitive and behavioral tests, such as the UHDRS motor subscale, Stroop Word test, and Montreal Cognitive Assessment, will be performed at intervals over the three years. Safety will be monitored through laboratory tests, ECGs, and tracking of adverse events. Participants must comply with study procedures including blood draws and MRI scans for the full duration up to the study end in May 2027.

Researchers are evaluating the safety, tolerability, and initial effects of SPK-10001 gene therapy in adults with Huntington's Disease. This randomized Phase 1/2 study aims to assess these aspects through a controlled, dose-escalation approach involving a one-time infusion into specific brain regions. The study focuses on participants aged 25 to 65 years who have confirmed genetic and clinical signs of Huntington's Disease. Participants will receive either the SPK-10001 gene therapy or a placebo surgery control in a randomized, quadruple-masked design. The gene therapy is administered as a single bilateral intraparenchymal infusion into the caudate and putamen. The study includes dose escalation and monitoring over several years to evaluate safety and early signs of efficacy. During the study, participants will be monitored for treatment-emergent adverse events for up to approximately five years. They will undergo assessments including the Unified Huntington's Disease Rating Scale Total Functional Capacity score and motor symptom progression measured by digital motor scores and composite scales at multiple time points up to 24 months. The study involves detailed safety and efficacy evaluations, with follow-up visits scheduled for long-term observation.

Researchers are investigating epilepsy-dyskinesia syndromes, which are rare genetic diseases causing both movement disorders and epilepsy in children. This multinational retrospective survey, supported by the International Parkinson and Movement Disorder Society, aims to collect detailed clinical and molecular data to better understand these conditions. The study focuses on identifying patterns in disease features, progression, and genetic links to improve knowledge and support precision medicine. The study collects previously recorded data from multiple countries, harmonizing information on clinical features, disease progression, age of onset, genetic variants, and coexisting neurological conditions. By standardizing this data, the survey addresses challenges in rare disease research like small, dispersed patient groups and inconsistent protocols. The goal is to build a shared clinical database and analyze how movement and seizure disorders relate at both clinical and molecular levels. Participants are children aged 0 to 18 years with diagnosed movement disorders linked to specific genetic variants. The study reviews existing medical records and genetic information without new treatments or interventions. Researchers will assess the disease spectrum, how movement disorders affect quality of life, and the effectiveness of symptomatic treatments over one year. The study encourages international collaboration to advance understanding and improve care for these rare conditions.

Researchers are studying spinocerebellar ataxia types 1 and 3 (SCA1 and SCA3) and Huntington's disease (HD), which are serious genetic neurodegenerative disorders without current treatments to slow their progression. This first-in-human trial evaluates a new drug called VO659, designed to target harmful gene mutations by binding to specific RNA sequences. The study aims to assess the safety, tolerability, and how the drug moves through and affects the body when given via spinal injections.

Researchers are evaluating ALN-HTT02, a drug given into the spinal fluid, in adults aged 25 to 70 years with stage 2 or early stage 3 Huntington's disease. The study aims to assess the safety, tolerability, how the drug moves through and affects the body (pharmacokinetics and pharmacodynamics), with a focus on single or repeat doses. This is a phase 1 randomized, double-blind, placebo-controlled trial sponsored by Alnylam Pharmaceuticals. Participants are randomly assigned to receive either a single dose of ALN-HTT02 or a placebo during the double-blind phase. Those who received the drug in this phase will not get another dose in the open-label phase, while those who received placebo can receive a single dose of ALN-HTT02 during the open-label phase. Afterward, all participants have the option to receive repeat doses in an open-label extension lasting up to 36 months. Throughout the study, participants will be monitored for adverse events for up to 12 months in each phase and up to 36 months during the extension. Researchers will measure mutant huntingtin protein levels in cerebrospinal fluid, and concentrations of ALN-HTT02 in plasma, cerebrospinal fluid, and urine at specified intervals. Safety, tolerability, and drug effects will be closely tracked over the course of the trial.

Researchers are evaluating the safety and tolerability of RG6496, a drug given in single ascending doses, in people who carry the gene expansion for Huntington's Disease. This first-in-human study is divided into two parts: Part 1 tests different dose levels in a randomized, placebo-controlled, double-blind design, followed by Part 2, an open-label extension where all eligible participants receive RG6496. In Part 1, participants receive either a single dose of RG6496 or a matching placebo, with dosing increasing in planned groups. Those who complete Part 1 and meet criteria may enter Part 2, where they receive one open-label dose of RG6496. The drug is administered intrathecally (into the spinal canal) under careful monitoring. Participants will be monitored up to approximately 24 months in Part 1 and up to 38 months in Part 2. Assessments include tracking adverse events, neurological function, cognitive testing with the Montreal Cognitive Assessment (MoCA), and suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS). Blood and cerebrospinal fluid samples will be collected to measure drug levels, immune response, and mutant huntingtin protein concentrations. Safety and tolerability will be closely observed throughout the study.

Researchers are evaluating the safety and tolerability of votoplam in people with early symptomatic Huntington's disease (HD) to see if it slows disease progression compared to a placebo. This study is a phase 3 randomized, double-blind trial sponsored by Novartis Pharmaceuticals. The investigation focuses on whether votoplam can impact disease measures over time in adults aged 21 to 70 who have genetically confirmed HD with specific clinical scores. Participants will be randomly assigned in a 3:2 ratio to receive either votoplam or a placebo, both taken orally. The study includes three periods: a screening period of up to 42 days to determine eligibility, a double-blind treatment period lasting up to 36 months, and a safety follow-up visit about 30 days after the end of treatment or study. Not all participants will complete the full 36 months of treatment. Throughout the study, participants will undergo various assessments including clinical rating scales such as the cUHDRS and UHDRS components, blood tests for mutant huntingtin protein and neurofilament light levels, and monitoring for adverse events. The main outcome measured is the change in the cUHDRS score from baseline to month 36. Safety follow-up will be conducted in person or by phone, ensuring close monitoring of participants during and after treatment.