Therapeutics

Telmisartan

Overview

Name: Telmisartan
Synonyms: Micardis
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

Background

Telmisartan is an angiotensin II receptor antagonist marketed around the world to treat elevated blood pressure and reduce the risk 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 United States. 

Angiotensin receptor antagonists 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, and have 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., 2008Mogi et al., 2008Kurata et al. 2014).

Findings

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 240 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 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 August 2018. 

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. 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 March 2018.

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References

Paper Citations

  1. . Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium. Biochem Biophys Res Commun. 2008 Aug 22;373(2):253-7. PubMed.
  2. . Telmisartan prevented cognitive decline partly due to PPAR-gamma activation. Biochem Biophys Res Commun. 2008 Oct 24;375(3):446-9. PubMed.
  3. . Telmisartan reduces progressive accumulation of cellular amyloid beta and phosphorylated tau with inflammatory responses in aged spontaneously hypertensive stroke resistant rat. J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):2580-90. Epub 2014 Sep 16 PubMed.

Further Reading

Papers

  1. . Angiotensin Mediated Oxidative Stress and Neuroprotective Potential of Antioxidants and AT1 Receptor Blockers. Mini Rev Med Chem. 2016 Oct 24; PubMed.
  2. . Differential effects of angiotensin II receptor blockers on Aβ generation. Neurosci Lett. 2014 May 1;567:51-6. Epub 2014 Mar 27 PubMed.
  3. . Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies. PLoS One. 2016;11(5):e0155823. Epub 2016 May 17 PubMed.
  4. . Systolic blood pressure variation and mean heart rate is associated with cognitive dysfunction in patients with high cardiovascular risk. Hypertension. 2015 Mar;65(3):651-61. Epub 2015 Jan 12 PubMed.
  5. . [Effects of telmisartan on the level of Aβ1-42, interleukin-1β, tumor necrosis factor α and cognition in hypertensive patients with Alzheimer's disease]. Zhonghua Yi Xue Za Zhi. 2012 Oct 23;92(39):2743-6. PubMed.
  6. . Ameliorative effects of telmisartan on the inflammatory response and impaired spatial memory in a rat model of Alzheimer's disease incorporating additional cerebrovascular disease factors. Biol Pharm Bull. 2012;35(12):2141-7. PubMed.