Abstract
Spinocerebellar ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Although the first disease-causing gene was identified nearly 30 years ago, there is no known cure to date, and only a few options exist for symptomatic treatment, with modest effects. The recently developed tools in molecular biology, such as CRISPR/Cas9 and antisense oligonucleotides, can directly act on the disease mechanisms at the genomic or RNA level in disease models. In a nutshell, we are finally just one step away from clinical trials with therapies targeting the underlying genetic cause. However, we still face the challenges for rare neurodegenerative diseases: difficulty in obtaining a large cohort size for sufficient statistical power and the need for biomarkers and clinical outcome assessments (COA) with adequate sensitivity to reflect progression or treatment responses. To overcome these obstacles, ataxia experts form research networks for clinical trial readiness. In this review, we retrace our steps of the collaborative efforts among ataxia researchers in the United States over the years to study and treat these relentless disorders and the future directions of such research networks.
Highlights
Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders involving the cerebellum with an autosomal-dominant pattern of inheritance
SCAs are monogenetic disorders with a high disease penetrance and defined clinical presentations with the core feature of cerebellar ataxia; SCAs can serve as disease models for novel disease-specific therapeutic approaches, such as gene therapies or antisense oligonucleotides (ASOs)
The major research challenges for orphan diseases are patient recruitment, development of reliable and responsive disease-specific clinical outcome assessment (COA) measures, collection of biosamples for biomarker discovery, uniform acquisition of brain imaging data, and the understanding of natural history. Addressing these challenges through collaborative research by a network of investigators specializing in such diseases is a powerful approach to establish clinical trial readiness
Summary
Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders involving the cerebellum with an autosomal-dominant pattern of inheritance. The major research challenges for orphan diseases are patient recruitment, development of reliable and responsive disease-specific clinical outcome assessment (COA) measures, collection of biosamples for biomarker discovery, uniform acquisition of brain imaging data, and the understanding of natural history. Addressing these challenges through collaborative research by a network of investigators specializing in such diseases is a powerful approach to establish clinical trial readiness. Spinocerebellar Ataxia Network in USA research networks and industries, several clinical trials for SCAs have been launched. These milestones for SCA research bring hope to SCA patients and their family members
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