Xanamem is an investigative therapy for Alzheimer’s disease that Actinogen Medical is developing. The treatment, previously known as UE2343, was originally developed by Corticrine, a subsidiary venture of the University of Edinburgh. Actinogen acquired Corticrine in 2014.

How Xanamem works

Xanamem is designed to reduce levels of the steroid hormone cortisol in the brain. It does this by blocking an enzyme called 11-beta‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which converts inactive cortisone to cortisol, the active hormone.

Cortisol is produced by the adrenal glands and is involved in a variety of functions such as metabolism and blood pressure. Cortisol levels fluctuate throughout the day and increase in response to stress.

A growing number of studies suggests a link between increased cortisol levels and Alzheimer’s disease.

For example, in a study of participants in the Baltimore longitudinal study of aging (BLSA), researchers found that increased cortisol levels in urine were associated with an increased risk of developing Alzheimer’s.

The Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) tracked 416 older adults with normal cognitive function for six years, looking at their blood cortisol levels, cognitive ability, and levels of beta-amyloid, a protein that forms plaques in the brains of Alzheimer’s patients. Study participants with accumulations of beta-amyloid in their brains had a greater cognitive decline if their cortisol levels were elevated, the researchers reported.

In mice with Alzheimer’s, treatment of the animals with a chemical that acts similarly to Xanamem, by inhibiting the 11β‐HSD1 enzyme prevented cognitive decline.

Xanamem in clinical trials

The University of Edinburgh completed a Phase 1 trial of UE2343 (NCT01770886) in 2013. The trial enrolled 48 healthy volunteers who took UE2343 in capsule form or a placebo. Researchers assessed the safety of UE2343 and how it is processed in the body.

Actinogen sponsored a second Phase 1 trial (NCT02616445) in 2015. Forty healthy volunteers were administered increasing doses of UE2343 or placebo. Researchers monitored the safety and tolerability of the treatment, as well as how it’s processed in the body. Blood and urine levels of cortisol were also measured.

Actinogen is currently recruiting patients with mild Alzheimer’s disease for a Phase 2 clinical trial (NCT02727699) to evaluate the safety, tolerability, and effectiveness of Xanamem. The trial, which the company is calling XanADu will enroll approximately 174 people at 20 sites in the U.S., Australia, and the U.K. 

Participants will take a capsule once a day containing 10 mg of Xanemem or a placebo for 12 weeks. Scoring on cognitive tests will be measured.

Other information

Actinogen said in a news release that it expects an independent safety board to release an interim report in May 2018 on the first 50 patients in its Phase 2 trial. The company expects to complete enrolling participants by the end of 2018 and to report results of the trial in the first half of 2019.

***

Alzheimer’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.