Profile of pridopidine and its potential in the treatment of Huntington disease: the evidence to date

Huntington disease (HD) is a chronic, genetic, neurodegenerative disease for which there is no cure. The main symptoms of HD are abnormal involuntary movements (chorea and dystonia), impaired voluntary movements (ie, incoordination and gait balance), progressive cognitive decline, and psychiatric di...

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Bibliographic Details
Published in:Drug design, development and therapy development and therapy, 2015-01, Vol.9, p.5827-5833
Main Authors: Squitieri, Ferdinando, de Yebenes, Justo Garcia
Format: Article
Language:English
Subjects:
Animals
Balance
Brain
Brain-derived neurotrophic factor
Cellular manufacture
Chorea
Clinical trials
Cognitive ability
Disease
Dopamine
Dopamine - metabolism
Dopamine Agents - pharmacology
Dopamine Agents - therapeutic use
Dosage and administration
Drug therapy
Dystonia
Gait
Gene expression
Genetic aspects
Growth factors
Health aspects
Humans
Huntingtin
Huntingtin Protein
Huntington Disease - drug therapy
Huntington Disease - genetics
Huntington Disease - physiopathology
Huntington's disease
Ligands
Medical research
Medical treatment
Metabolism
Mutation
Nerve Tissue Proteins - genetics
Neurodegenerative diseases
Neurological diseases
Neuroprotection
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
Pharmacology
Piperidine
Piperidines - pharmacology
Piperidines - therapeutic use
Polyglutamine
Proteins
Psychiatry
Receptors
Signs and symptoms
Stabilizers (agents)
Transcription
Trinucleotide repeats
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Description
Summary:Huntington disease (HD) is a chronic, genetic, neurodegenerative disease for which there is no cure. The main symptoms of HD are abnormal involuntary movements (chorea and dystonia), impaired voluntary movements (ie, incoordination and gait balance), progressive cognitive decline, and psychiatric disturbances. HD is caused by a CAG-repeat expanded mutation in the HTT gene, which encodes the huntingtin protein. The inherited mutation results in the production of an elongated polyQ mutant huntingtin protein (mHtt). The cellular functions of the Htt protein are not yet fully understood, but the functions of its mutant variant are thought to include alteration of gene transcription and energy production, and dysregulation of neurotransmitter metabolism, receptors, and growth factors. The phenylpiperidines pridopidine (4-[3-methanesulfonyl-phenyl]-1-propyl-piperidine; formerly known as ACR16) and OSU6162 ([S]-[-]-3-[3-methane [sulfonyl-phenyl]-1-propyl-piperidine) are members of a new class of pharmacologic agents known as "dopamine stabilizers". Recent clinical trials have highlighted the potential of pridopidine for symptomatic treatment of patients with HD. More recently, the analysis of HD models (ie, in vitro and in mice) highlighted previously unknown effects of pridopidine (increase in brain-derived neurotrophic factor, reduction in mHtt levels, and σ-1 receptor binding and modulation). These additional functions of pridopidine suggest it might be a neuroprotective and disease-modifying drug. Data from ongoing clinical trials of pridopidine will help define its place in the treatment of HD. This commentary examines the available preclinical and clinical evidence regarding the use of pridopidine in HD.
ISSN:1177-8881
1177-8881
DOI:10.2147/DDDT.S65738