Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Current Therapeutic Advances in Patients and Experimental Models of Huntington's Disease

Author(s): Ana C. Brett, Tatiana R. Rosenstock and A. Cristina Rego

Affiliation: Center for Neuroscience and Cell Biology and Faculty of Medicine, Rua Larga, University of Coimbra (polo I), 3004-504 Coimbra, Portugal.

Keywords: Huntington disease, mutant huntingtin, neuroprotective therapy, symptomatic treatment.

Abstract:

Huntington’s disease (HD) clinical manifestations begin insidiously and are progressively incapacitating. Symptomatic therapies, in particular dopamine blockers and neuroleptics, are presently the only treatment for HD. Identification of neuropathological mechanisms that underlie the selective striatal and cortical neurodegeneration has allowed for the development of novel neuroprotective therapies that may improve HD patients’ quality of life and enhance their survival. In this review we describe the symptomatic and neuroprotective therapies in HD that are currently in a preclinical or clinical stage. Neuroprotective therapies can act at several stages of HD, namely through: i) transcription modulation, ii) regulation of neurotrophic factors levels, iii) inhibition of metabolic dysfunction through metabolic enhancers, iv) apoptosis inhibition, v) autophagy regulation, vi) transglutaminase inhibition, and/or vii) modulation of neurotransmitter receptors. Moreover, emerging therapies in HD, including gene therapy using siRNA and shRNA to silence CAG repeats or deep brain stimulation, have shown promising results. Although most of the therapies are at a pre-clinical stage, phase II-III clinical trials have been performed for each pathophysiological mechanism of the disease. Thus, efforts should continue to ensure that effective therapies are studied and tested to help mitigate HD.

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Article Details

VOLUME: 15
ISSUE: 3
Page: [313 - 334]
Pages: 22
DOI: 10.2174/1389450114666131124140704