deutetrabenazine for the treatment of chorea associated with Huntington’s disease

Gupta, Harshit; Perkins, Wil; Stark, Cain W.; Kikkeri, Sathya; Kakazu, Juyeon; Kaye, Adam M.; Kaye, Alan D.

doi:10.52965/001c.36040

Cited by 6 publications

(3 citation statements)

References 33 publications

(61 reference statements)

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“…In 2015, Teva Pharmaceuticals acquired the rights from Auspex Pharmaceuticals, and deutetrabenazine was approved by the FDA for the treatment of both chorea in 2017 (ref. 79 ) and tardive dyskinesia the following year 6 . Conversely, trials evaluating both fixed 80 and flexible 81 doses of this heavy drug for the treatment of Tourette syndrome did not meet the primary end point.…”

Section: Deuterium Switches Approved So Farmentioning

confidence: 99%

Deuterium in drug discovery: progress, opportunities and challenges

Martino

Maxwell

Pirali

2023

Nat Rev Drug Discov

125

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Substitution of a hydrogen atom with its heavy isotope deuterium entails the addition of one neutron to a molecule. Despite being a subtle change, this structural modification, known as deuteration, may improve the pharmacokinetic and/or toxicity profile of drugs, potentially translating into improvements in efficacy and safety compared with the non-deuterated counterparts. Initially, efforts to exploit this potential primarily led to the development of deuterated analogues of marketed drugs through a ‘deuterium switch’ approach, such as deutetrabenazine, which became the first deuterated drug to receive FDA approval in 2017. In the past few years, the focus has shifted to applying deuteration in novel drug discovery, and the FDA approved the pioneering de novo deuterated drug deucravacitinib in 2022. In this Review, we highlight key milestones in the field of deuteration in drug discovery and development, emphasizing recent and instructive medicinal chemistry programmes and discussing the opportunities and hurdles for drug developers, as well as the questions that remain to be addressed.

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Section: Deuterium Switches Approved So Farmentioning

confidence: 99%

Deuterium in drug discovery: progress, opportunities and challenges

Martino

Maxwell

Pirali

2023

Nat Rev Drug Discov

125

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“…Ref. [148] (2021) provides examples of approved and unapproved drugs repurposed for the treatment of chorea in HD: tetrabenazine (Xenazine ® ) [149] and Austedo (deutetrabenazine), which is a compound with VMAT2 inhibitor activity [150]. Not yet approved substances include cysteamine bitartrate and lithium citrate tetrahydrate.…”

Section: Drug Repurposing For Hd Treatmentmentioning

confidence: 99%

Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing

Makeeva,

Dyrkheeva,

Lavrik

et al. 2023

IJMS

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The spectrum of neurodegenerative diseases known today is quite extensive. The complexities of their research and treatment lie not only in their diversity. Even many years of struggle and narrowly focused research on common pathologies such as Alzheimer’s, Parkinson’s, and other brain diseases have not brought cures for these illnesses. What can be said about orphan diseases? In particular, Huntington’s disease (HD), despite affecting a smaller part of the human population, still attracts many researchers. This disorder is known to result from a mutation in the HTT gene, but having this information still does not simplify the task of drug development and studying the mechanisms of disease progression. Nonetheless, the data accumulated over the years and their analysis provide a good basis for further research. Here, we review studies devoted to understanding the mechanisms of HD. We analyze genes and molecular pathways involved in HD pathogenesis to describe the action of repurposed drugs and try to find new therapeutic targets.

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“…Additionally, VMAT2 inhibitors are used to treat dyskinesias caused by neuroleptic drugs or other diseases [ 55 ]. For example, tetrabenazine is utilized in the treatment of tardive dyskinesia, a movement disorder that can be caused by prolonged use of antipsychotic medications, and chorea associated with neurodegenerative diseases such as Huntington's disease [ 56 , 57 ]. VMAT2 is also used to identify the functionality of catecholaminergic TH positive neurons.…”

Section: Introductionmentioning

confidence: 99%