Synonyms: Rasagiline mesylate, Azilect, TVP-1012
Chemical Name: 1H-Inden-1-amine-2,3-dihydro-N-2-propynyl-(1R)-methanesulfonate
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis
U.S. FDA Status: Alzheimer's Disease (Phase 2), Parkinson's Disease (Approved), Amyotrophic Lateral Sclerosis (Inactive)
Rasagiline is a selective monoamine oxidase B (MAOB) inhibitor widely used to treat symptoms of Parkinson’s disease. It works by blocking the breakdown of dopamine, thus increasing dopaminergic function in the brain. Rasagiline was approved for marketing in Europe in 2005 and in the United States in 2006.
MAOB activity was reported to be increased in Alzheimer’s disease brain, mainly in reactive astrocytes near amyloid plaques (Saura et al., 1994; Gulyás et al., 2011). Monoamine oxidase contributes to the generation of reactive oxygen species, leading to a suggestion that inhibiting this enzyme might delay progression of AD by reducing oxidative stress in the brain (Weinreb et al., 2010). Rasagiline has been reported to exhibit anti-apoptotic, neuroprotective activity, and to promote the non-amyloidogenic processing of APP (Youdim and Weinstock, 2001).
From 2004 to 2007, Teva Pharmaceuticals Industries and Eisai collaborated on a Phase 2, placebo-controlled trial of rasagiline versus placebo in people with mild to moderate AD who were taking Aricept. The multicenter trial enrolled 376 participants who were treated for one year with 1 or 2 mg rasagiline daily or placebo, and 10 mg Aricept. The primary endpoint was cognition. The companies ended their collaboration in July 2006, and no results or further information about the trial are available.
In May 2015, Cleveland Clinic researchers began a small, Phase 2 proof-of-concept study to gauge whether rasagiline might improve regional brain metabolism measured by FDG-PET in people with AD. The trial enrolled 50 volunteers clinically diagnosed with mild to moderate AD and FDG-PET findings consistent with AD; no Aβ- or tau-based markers were used to confirm their diagnoses. Participants received rasagiline titrated to 1 mg daily or placebo for 24 weeks, plus four weeks of follow-up. The primary endpoint was change in FDG-PET over 24 weeks. Results were presented at the 2019 CTAD conference, and published after peer review (Dec 2019 conference news; Matthews et al., 2021). Forty-three people completed the trial. It met its primary endpoint, with glucose metabolism declining less in frontal, anterior cingulate, and striatal regions in the treated group compared with placebo. On exploratory clinical measures, the treated group significantly improved on the Quality of Life-AD (QOL-AD) test, and showed trends to better performance on six of seven other cognitive tests. Tau PET was also performed; higher tangle load at baseline correlated with more cognitive decline in the placebo group, and a larger effect of rasagiline in the treatment group.
In a trial of 170 people with Parkinson’s disease and mild cognitive impairment, 24 weeks of 1 mg rasagiline daily did not improve cognitive function (Weintraub et al., 2016). Rasagiline was also evaluated in ALS (Ludolph et al., 2018), schizophrenia (Buchanan et al., 2015), multiple-system atrophy (Poewe et al., 2015), PSP (Nuebling et al., 2016), serotonin syndrome, and retinal detachment.
A different MAOB inhibitor, sembragiline, also posted negative results in an Alzheimer's disease trial (Jul 2015 news).
Rasagiline improved blood flow in a separate small study of 11 people with AD treated for a median of 1.7 years with 1 mg per day, along with donepezil. Compared to untreated age- and sex-matched controls, the treated group had increased perfusion, as measured by SPECT, in the cingulate gyrus and right inferior gyrus regions of the cortex. The study did not measure cognition (Song et al., 2020).
For details on rasagiline trials in Alzheimer's, see clinicaltrials.gov.
Last Updated: 10 May 2021
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