Current Therapeutic Advances in Patients and Experimental Models of Huntington's Disease
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.
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.
Keywords: Huntington disease, mutant huntingtin, neuroprotective therapy, symptomatic treatment.
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