Spinocerebellar Ataxia Type 1

The goal of this first-in-human clinical trial is to assess the safety and tolerability of four doses of a new study drug called VO659 in people with genetic disorders called spinocerebellar ataxia type 1, type 3 or Huntington's disease. Another aim is to determine the concentrations of the study drug in the cerebral spinal fluid and blood after single and multiple doses. Study drug will be administered by lumbar intrathecal bolus injections.

Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor coordination, and speech difficulties. There are different kinds of SCAs and this study will focus on types 1, 2, 3, 6, 7, 8, 10, 27B, and RFC1-ataxia (SCA 1, SCA 2, SCA 3, also known as Machado-Joseph disease, SCA 6, SCA 7, SCA 8, SCA 10, SCA27B, and RFC1-ataxia, also known as CANVAS). The diseases are rare, slowly progressive, cause increasingly severe neurological difficulties, and are variable across and within genotypes. The purpose of this research study is to bring together a group of experts in the field of SCA for the purpose of learning more about the disease. The research questions are: 1. How do these diseases progress over time? 2. What are the best ways to measure the progression? 3. Do some genes, other than the gene that is abnormal in these diseases, have any effect on the way the disease behaves? This is a nationwide study and the investigators expect that 1400 patients will participate all over North America. The participants will remain in the study for an indeterminate period of time, for as long as they are willing to participate. Study visits will be done every 12 months. Within the broader CRC-SCA, there is an Imaging Sub-study aiming to identify magnetic resonance imaging (MRI) markers sensitive to the onset and progression of common SCAs. To accomplish this, participants attend annual visits involving a neurological exam, surveys, a blood draw, and an MRI scan. Participants can attend visits at one of three US locations - Minneapolis, MN; Gainesville, FL; or Dallas, TX and two European locations - Paris, France and Bonn, Germany. Eligible participants must either have SCA1, 2, or 3 or have been a participant of the previous READISCA study (NCT03487367). Gene-positive participants must have a SARA score less than 10; however, there is no SARA limit for participants previously enrolled in READISCA. All participants must be 18 years or older. Gene-negative participants should be 25-65 years old.

The purpose of this study is verify the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSC) therapy for patients with Spinocerebellar Ataxia, and in addition, explore the possible mechanisms of UC-MSC therapy in Spinocerebellar Ataxia.

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.