Investigational agents for the management of Huntington’s disease

ABSTRACT

Introduction: An inherited, chronic progressive, neurodegenerative disorder is Huntington’s disease, characterized by motor, cognitive, and psychiatric symptoms. Predictive genetic testing allows earlier diagnosis and identification of gene carriers for Huntington’s disease. These individuals are ideal candidates for testing of therapeutic interventions for disease modification.

Areas covered: According to queries in Pubmed, Embase and clinical register databases, research and clinical studies emerge on symptomatic and neuroprotective therapies in Huntington’s disease. This review discusses novel agents for symptomatic therapy and disease modification. They are currently in phase I and II of drug development

Expert opinion: There are promising, safe and well tolerated compounds for amelioration of motor and neuropsychiatric symptoms, but their efficacy still needs to be proven in clinical trials. Deterioration of mutant huntingtin expression, antiapoptotic or cell death inhibition as disease modifying concepts was efficacious in models of Huntington’s disease. However, the risk for clinical trial failures is high not only due to ineffectiveness of the tested agent. Negative study outcomes may also result from design misconceptions, underestimation of the heterogeneity of Huntington’s disease, too short study durations and too small study cohorts.

KEYWORDS:

• Huntington’s disease
• study design
• tetrabenazine
• neuroprotection
• disease modification
• symptomatic treatment

Article highlights

• Predominant chorea-like, abnormal movement patterns in combination with cognitive and psychiatric disturbances influence the life of patients with Huntington’s disease and their carers.

• Outcomes of clinical trials on amelioration of symptoms may also be biased by the heterogeneity of Huntington’s disease and the effects of a patient tailored drug therapy, both of which may interfere with the efficacy of the tested compound.

• Predictive genetic testing allows prodromal diagnosis of Huntington’s disease, which is an ideal precondition for testing of potentially disease course modifying agents.

• Determining the effect of investigational drugs for patients with Huntington’s disease may be more appropriate in familiar surroundings over longer intervals, for instance with objective tools like telemedicine guided movement analysers.

• Therapy of chronic neurodegenerative disorders, such as Huntington’s disease, is an individually to the disease process adapted application of therapies combined with continuous and critical evaluation of the value of these interventions by patients, caregivers and physicians.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.