Huntington's disease: Current and future therapeutic prospects

Abstract

Huntington's disease is a progressive neurodegenerative disorder for which therapies are woefully inadequate and do not prevent inevitable progression. Currently approved therapies are primarily aimed at treating chorea, but do not address the more clinically meaningful motor, behavioral, and cognitive features of the disease. However, there are a number of promising new therapies that are currently being studied in the laboratory, and in the clinic. This article will review the wide variety of therapies currently being tested, the advances in clinical trials and end points, and the many potentially relevant new targets. © 2018 International Parkinson and Movement Disorder Society.

Alterations in synaptic function and plasticity in Huntington disease

“…Early results indicate that pridopidine shows a trend towards improving motor abnormalities in clinical trials (Kieburtz et al, 2018), supporting the hypothesis that dopamine stabilisation can improve the movement disorder of HD.…”

Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species

“…Huntington's disease is a genetic neurodegenerative disorder characterized by the selective degeneration of neurons. This degeneration results in progressive disabilities, including motor dysfunction and both cognitive and psychiatric de iciencies [104][105][106]. HD is associated with polyglutamine-expansion; thus, the disease primarily impacts the cerebral cortex and striatum [107,108].…”

New tricks for an old dog: A repurposing approach of apomorphine

“…Dysfunction of central dopaminergic pathways are also described, with biphasic changes (Cepeda et al, 2014;Schwab et al, 2015): in early stages, dopamine neurotransmission is enhanced, leading to hyperkinetic movements, whereas late stages are more characterized by dopaminergic deficits (Cepeda et al, 2014). As quality of life is profoundly affected, management involves a combination of pharmacological and non-pharmacological interventions (Vitale et al, 2007;McColgan & Tabrizi, 2018;Kieburtz et al, 2018). Promising preclinical approaches targeting excitotoxicity, mitochondrial dysfunction or inflammation have failed to show efficacy in clinical trials (Kieburtz et al, 2018) and, to date, no therapy can meaningfully control nor prevent HD devastating evolution (McColgan & Tabrizi, 2018;Kieburtz et al, 2018).…”

“…As quality of life is profoundly affected, management involves a combination of pharmacological and non-pharmacological interventions (Vitale et al, 2007;McColgan & Tabrizi, 2018;Kieburtz et al, 2018). Promising preclinical approaches targeting excitotoxicity, mitochondrial dysfunction or inflammation have failed to show efficacy in clinical trials (Kieburtz et al, 2018) and, to date, no therapy can meaningfully control nor prevent HD devastating evolution (McColgan & Tabrizi, 2018;Kieburtz et al, 2018). Gene-directed therapies appears to be one of the most promising approach currently investigated (Cepeda et al, 2014;Kieburtz et al, 2018).…”