Human cerebellar deep brain stimulation and recordings in spinocerebellar ataxias - individuals with spinocerebellar ataxia (SCA) suffer from incapacitating symptoms, including imbalance, frequent…

The National Institute of Neurological Disorders and Stroke (NINDS) awarded Columbia University's Health Sciences Division a $1,225,804 Cooperative Agreement on September 9, 2025, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). The award supports a Phase 1 clinical study investigating bilateral cerebellar deep brain stimulation (DBS) targeting the deep cerebellar nuclei (DCN) as a potential therapeutic intervention for individuals with spinocerebellar ataxia types 1 and 3 (SCA1 and SCA3). The research builds on promising preclinical findings and preliminary evidence from international case studies demonstrating that cerebellar DBS may alleviate motor deficits associated with cerebellar ataxia. The study will assess safety and preliminary efficacy of this neuromodulation approach while utilizing temporary lead externalization and neural recording capabilities to advance understanding of human DCN physiology, ultimately informing the design of subsequent larger-scale clinical trials.

Columbia University's research performance is supported by a sub-award to Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, which was sub-granted on December 11, 2025. Cleveland Clinic's contribution encompasses comprehensive Phase 1 clinical trial support including regulatory preparation, FDA Investigational Device Exemption milestone management, enrollment procedures, informed consent monitoring, participant candidacy evaluation, DBS device programming, behavioral assessments, neuroimaging and lead localization, statistical analysis, database development, ethics oversight, and interpretation of cerebellar DBS and deep cerebellar nuclei recording data. The cooperative structure leverages both institutions' clinical and research expertise to execute this rigorous translational neuroscience investigation, with performance scheduled for completion by August 31, 2026.

Human cerebellar deep brain stimulation and recordings in spinocerebellar ataxias - individuals with spinocerebellar ataxia (SCA) suffer from incapacitating symptoms, including imbalance, frequent falls, and loss of movement control. No therapies currently exist to treat cerebellar ataxia symptoms in SCA patients because the intricate cerebellar circuit dysfunction across different SCA types poses a significant challenge for pharmacological therapeutic development. Despite the complexity of the cerebellar circuit, IT is uniquely organized, with all the circuit computation ultimately going through a single output- the deep cerebellar nuclei (DCN), representing a pivotal target for neuromodulation. Over the past 5 years, studies in animal models showed promising results that cerebellar deep brain stimulation (DBS) targeting DCN could alleviate ataxia-like motor deficits, paving the way for the initiation of clinical trials in patients. Importantly, a preliminary case series conducted in brazil supported the early efficacy of cerebellar DCN DBS in improving cerebellar ataxia symptoms in human patients, especially two individuals with SCA3. However, in order to realize the ultimate goal of utilizing cerebellar DBS as a clinical treatment to improve lives of SCA patients, IT is imperative to conduct a rigorous phase 1 clinical trial in the united states, which will inform the design of subsequent, larger trials. In addition, we will need to know if cerebellar DBS can be effective across different SCA types with different cerebellar circuit involvement to determine the patient selection criteria in the future. To this end, we propose to initiate a phase 1 study of bilateral cerebellar DBS for individuals with SCA1 and SCA3 to assess its safety and preliminary efficacy (aim 1). Moreover, we will use temporary lead externalization and a DBS system that is capable of recording neural activity to gain an understanding of human DCN physiology. Those data will be synchronized to cerebello-cortical electroencephalogram to gain insights into network effects of cerebellar DBS (aim 2). The knowledge of human neural activity linked to cerebellar ataxia severity and the circuit responses to cerebellar DBS holds the promise to refine DBS parameters based on neural activity in the future. Our research will offer valuable insights for making decisions regarding the further development of cerebellar DBS for SCA patients and will advance the knowledge of human cerebellar physiology.