Current and emerging treatment modalities for spinocerebellar ataxias

ABSTRACT

Introduction

Spinocerebellar ataxias (SCA) are a group of rare neurodegenerative diseases that dramatically affect the lives of affected individuals and their families. Despite having a clear understanding of SCA’s etiology, there are no current symptomatic or neuroprotective treatments approved by the FDA.

Areas covered

Research efforts have greatly expanded the possibilities for potential treatments, including both pharmacological and non-pharmacological interventions. Great attention is also being given to novel therapeutics based in gene therapy, neurostimulation, and molecular targeting. This review article will address the current advances in the treatment of SCA and what potential interventions are on the horizon.

Expert Opinion

SCA is a highly complex and multifaceted disease family with the majority of research emphasizing symptomatic pharmacologic therapies. As pre-clinical trials for SCA and clinical trials for other neurodegenerative conditions illuminate the efficacy of disease modifying therapies such as AAV-mediated gene therapy and ASOs, the potential for addressing SCA at the pre-symptomatic stage is increasingly promising.

KEYWORDS:

• Spinocerebellar ataxia
• treatment
• neurodegenerative diseases
• gene therapy
• neurostimulation

Article highlights

• Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited, progressive disorders marked by cerebellar degeneration

• Currently, there are no symptomatic or neuroprotective treatments approved by the United States (US) Food and Drug Administration (FDA) for SCAs

• Research efforts have focused on symptomatic and pharmacologic treatments for SCA, with the majority of clinical trials involving oral pharmaceutical agents

• Emerging disease modifying therapies are being developed, such as AAV-mediated gene therapy and ASOs to address SCA at its source

• Biomarker identification can facilitate therapy development and thus must continue to take high priority in SCA research

Declaration of interests

SH Kuo received research funding from National Institutes of Health and National Ataxia Foundation. SH Kuo also serves as a consultant for Praxis, Neurocrine, uniQure, and Sage Therapeutics. TA Zesiewicz has received personal compensation for serving on the advisory boards of Boston Scientific; Reata Pharmaceuticals, Inc; and Steminent Biotherapeutics. TA Zesiewicz has received personal compensation as senior editor for Neurodegenerative Disease Management and as a consultant for Steminent Biotherapeutics. Dr Zesiewicz has received royalty payments as co-inventor of varenicline for treating imbalance (patent number 9,463,190) and nonataxic imbalance (patent number 9,782,404). TA Zesiewicz has received research/grant support as principal investigator/investigator for studies from AbbVie Inc; Biogen; Biohaven Pharmaceutics; Boston Scientific; Bukwang Pharmaceuticals Co, Ltd; Cala Health, Inc; Cavion; Friedreich’s Ataxia Research Alliance; Houston Methodist Research Institute; National Institutes of Health (READISCA U01); Retrotope Inc; and Takeda Development Center Americas, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.