Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Boehringer Ingelheim
Approved for: Hypertension
Telmisartan is an angiotensin II receptor antagonist marketed around the world to treat elevated blood pressure and reduce the possibility of cardiovascular risk associated with chronic hypertension. Telmisartan is an alternative medication for people who are unable to take angiotensin-converting enzyme (ACE) inhibitors. In March 2014, a generic version became available in the U.S.
Angiotensin receptor blockers (ARBs) have been linked to reduced risk of AD. They act on the renin-angiotensin system, which regulates blood pressure in the body and the brain. Angiotensin II receptors also mediate inflammation, blood-brain barrier maintenance, and neuron survival. Genetic, epidemiologic and biological evidence implicates changes in the brain renin-angiotensin system in Alzheimer’s disease (reviewed in Kehoe 2018). ARB use is associated with a reduced incidence of cognitive impairment, dementia, and AD (e.g., Wharton et al., 2015; Barthold et al., 2020; also see Walker et al., 2020).
In people with mild cognitive impairment, use of ARBs, but not other antihypertensives, is linked to lower brain amyloid load and CSF tau (Hajjar et al., 2012; Hajjar et al., 2015).
Telmisartan has been proposed to slow AD pathogenesis by controlling cerebral blood flow, protecting the cerebral microvasculature, and reducing plaque formation in the brain (e.g., Baden et al., 2008; Mogi et al., 2008; Kurata et al., 2014).
Two clinical trials are evaluating telmisartan in Alzheimer's disease, both sponsored by academic medical centers, not the drug maker.
In spring 2014, a Phase 2 open-label drug repurposing study sponsored by the Alzheimer's Drug Discovery Foundation started up at three locations in Ontario, Canada. It enrolls 150 people with a clinical diagnosis of mild to moderate AD supported by an MRI scan consistent with that diagnosis. Participants take a one-year course of 40 or 80 mg of telmisartan or, as a comparator, 2, 4, or 8 mg per day of the angiotensin converting enzyme inhibitor ACEI and the antihypertensive drug perindopril. The primary outcome, besides safety, is ventricular enlargement as measured by MRI, to assess whether telmisartan slowed brain atrophy. Secondary outcomes are hippocampal, gray/white matter volume, and cognitive and functional measures. This trial is set to run until March 2022.
A Phase 1 study, sponsored by Emory University, started in April 2015 to enroll an estimated 66 middle-aged African Americans who are at risk of Alzheimer's disease due to having both hypertension and a parent with Alzheimer's (Wharton et al., 2018). The study will compare an eight-month course of either 20 mg or 40 mg telmisartan once daily to placebo for change in CSF angiotensin metabolites. Secondary outcomes include plasma biomarkers of the renin-angiotensin system, CSF markers of Aβ and tau, as well as various cognitive tests and structural and perfusion MRI. This trial will run until June 2020.
For details, see clinicaltrials.gov.
Last Updated: 23 Oct 2020
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