Cerebellar DBS in SCA1 and SCA3 Study

People with spinocerebellar ataxia (SCA) face progressively disabling symptoms such as poor balance, frequent falls, and a loss of muscle control. Currently, there are no approved treatments for these symptoms.

Developing medications to treat SCA is incredibly difficult because the brain's movement center-the cerebellum-has complex, damaged wiring that varies between patients. However, all signals from this complex brain region flow through a single exit point called the deep cerebellar nuclei (DCN). This makes the DCN (specifically, the dentate nucleus or DN) a perfect target for brain stimulation. Over the past five years, animal studies have shown that using a device to stimulate this area (called deep brain stimulation, or DBS) can significantly improve movement control. Recently, a small study showed promising early results in humans, particularly in two patients with SCA type 3.

To translate these findings into a standard treatment that has the potential to improve patients' lives, the investigators must first determine whether this is feasible and safe. The investigators will also need to see if this treatment works for different types of SCA, since cerebellar damage varies from person to person. Therefore, the aim of this study is to test and safety, feasibility, and early effectiveness of DBS on both sides of the brain in 12 people with SCA types 1 and 3. During the study, the investigators will use temporary external wires and a brain-recording device to listen to the brain's signals. By matching these signals with standard brain wave tests (EEGs), the investigators will hopefully understand exactly how this stimulation fixes the brain's movement network.

Inclusion criteria

• Subject is aged >= 18 years and =< 60 years.
• Subject has moderate ataxia severity, as demonstrated by a Scale for Ataxia Rating and Assessment (SARA) score >= 11.
• Subject has genetic confirmation of pathological repeat expansions in ATXN1 (for SCA1, repeat size >= 40) and ATXN3 (for SCA3, repeat size >= 56).
• Subject has been on a stable and optimized standard of care (SoC) regimen for at least 3 months prior to Screening (including physical therapy) and continues to exhibit signs of cerebellar ataxia.
• Subject has a minimum 6th grade reading level, as determined by the Rapid Estimate of Adult Literacy in Medicine (REALM) scale.
• Subject is able and willing to give informed consent and attend all study visits.
• Subject is available for all follow-up visits during the length of the study.

Exclusion criteria

• Subject is unable to provide informed consent.
• Subject has presence of overt tremor, dystonia, and/or parkinsonism, which are atypical features and could be suggestive of prominent extra-cerebellar circuit involvement that may not respond well to cerebellar DBS.
• Subject is wheelchair dependent and may be too progressed to complete gait assessments.
• Subject is unable to stop anticoagulation or platelet anti-aggregation therapy for study procedures.
• Subject has a Montreal Cognitive Assessment (MoCA) score =< 24.
• Subject has a diagnosis of epilepsy.
• Subject has a major active psychiatric illness that may interfere with the study, such as psychiatric disorders or severe personality disorders.
• Subject has an untreated or inadequately treated major depressive episode.
• Subject is pregnant, lactating, or planning to become pregnant during the study.
• For women of childbearing potential, subject is unable or unwilling to use accepted contraception methods.
• Subject is unable to communicate with investigators or staff.
• Subject has contraindications to DN DBS, including significant small vessel ischemic disease, vertebrobasilar vascular disease, and/or any other structural abnormalities of the cerebellum, cerebellar peduncles, and brain stem that would preclude safe placement of the DBS leads.
• Subject has contraindications to magnetic resonance (MR) imaging, e.g., weight incompatible with scanner, implanted metallic devices or electrical devices (pacemaker, defibrillator, spinal cord stimulator), or intolerance to MRI contrast agents.
• Subject is enrolled in another device, biologic or pharmaceutical study within 30 days of consent in the current study (i.e., patients cannot be enrolled if participation in another study was not completed at least 30 days prior to consent).
• Subject has evidence of behavior(s) consistent with alcohol or substance abuse/dependence within the preceding 6 months, as outlined by the DSM-V criteria.
• Subject has a condition that, in the opinion of the investigator, would significantly increase the risk for interference with study compliance, safety, or outcome.
• Subject is at risk for suicide, defined by a total score >= 3 on the Columbia Suicide Severity Rating Scale (C-SSRS).
• Patients who are not able to read, speak and/or understand English.