: Huntington's disease (HD)-associated chorea and tardive dyskinesia (TD) are hyperkinetic movement disorders that can have deleterious effects on patients' quality of life (QoL). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of HD-associated chorea and TD. It is structurally similar to tetrabenazine, an FDA-approved compound for treatment of chorea that is widely used off-label for treatment of TD, but has deuterium modifications that improve its pharmacokinetic profile.: Herein, the authors cover the key clinical trials with deutetrabenazine in patients with HD-associated chorea (First-HD and ARC-HD) and in patients with TD (ARM-TD, AIM-TD, and RIM-TD).: Deutetrabenazine demonstrates consistent efficacy across patient types regardless of underlying psychiatric illness, or through use of dopamine-receptor antagonists (DRAs), which are the primary cause of TD. The safety profile of deutetrabenazine in clinical trials is similar to that of placebo. Long-term extension studies in both HD-associated chorea and TD show consistent efficacy and safety. Deutetrabenazine will likely be an integral part of the treatment strategy for HD-associated chorea and TD. Meanwhile, its potential to treat other hyperkinetic movement disorders is still under investigation.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1080/14656566.2019.1674281 | DOI Listing |
Nat Commun
January 2025
Center for Biomolecular and Cellular Structure, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
Toxic protein aggregates are associated with various neurodegenerative diseases, including Huntington's disease (HD). Since no current treatment delays the progression of HD, we develop a mechanistic approach to prevent mutant huntingtin (mHttex1) aggregation. Here, we engineer the ATP-independent cytosolic chaperone PEX19, which targets peroxisomal membrane proteins to peroxisomes, to remove mHttex1 aggregates.
View Article and Find Full Text PDFExpert Rev Neurother
September 2024
Neurology and Neurosurgery, Movement Disorders Neuromodulation & Brain Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Introduction: Tardive dyskinesia (TD) and Huntington's disease (HD)-associated chorea are persistent and disabling hyperkinetic disorders that can be treated with vesicular monoamine transporter type 2 (VMAT2) inhibitors, including the recently approved once-daily (QD) formulation of deutetrabenazine (DTBZ ER). While its efficacy and safety profile have not been directly investigated, currently available data confirms bioequivalence and similar bioavailability to the twice-daily formulation (DTBZ BID).
Areas Covered: The authors briefly review the pivotal trials establishing efficacy of DTBZ for TD and HD-associated chorea, the pharmacokinetic data for bioequivalence between QD and BID dosing of DTBZ, as well as dose proportionality evidence, titration recommendations, and safety profile for DTBZ ER.
Neurotoxicology
May 2024
Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, M.S. 441 002, India. Electronic address:
Huntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties.
View Article and Find Full Text PDFLife Sci
February 2024
Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Aims: Endoplasmic reticulum stress (ERS) with aberrant mitochondrial-ER contact (MERC), mitophagy, and apoptosis are interconnected determinants in neurodegenerative diseases. Previously, we proved the potential of Morin hydrate (MH), a potent antioxidant flavonoid, to mitigate Huntington's disease (HD)-3-nitropropionic acid (3-NP) model by modulating glutamate/calpain/Kidins220/BDNF trajectory. Extending our work, we aimed to evaluate its impact on combating the ERS/MERC, mitophagy, and apoptosis.
View Article and Find Full Text PDFClin Genet
April 2024
ALS Centre, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
Recently, pathogenic expansions (range 40-64 CAG repeats) in the HTT gene have been found in patients diagnosed with pure frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). We report a mother with Huntington's disease (HD) associated with motor neuron disease (MND) signs and her daughter suffering from ALS with subtle signs of HD, both carrying a pathogenic allele of the HTT gene (i.e.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!