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A drug licensed for lymphoma and used to treat several forms of cancer may also be an effective anti-Alzheimer's agent, new research has revealed.
Bexarotene, marketed as Targretin, is licensed for the treatment of a disease called cutaneous T cell lymphoma, although it has also been used subsequently to suppress the growth of a number of other cancers including breast and lung malignancies. But owing to the way the agent works, by activating a signalling molecule called a retinoid X receptor (RXR) which is present on DNA and controls gene expression, animal experiments have now demonstrated that it can also dissolve the amyloid plaques that cause Alzheimer's and reverse some of the cognitive deficits associated with the disease.
Writing in Science, Case Western Reserve University researcher Gary Landreth and his team administered the agent to mice genetically programmed to develop the rodent equivalent of Alzheimer's. Treated juvenile animals showed a near immediate 25% drop in the levels of dissolved beta-amyloid proteins in the fluid bathing their brain cells. After 14 days of therapy, the number of amyloid deposits was down by 75% compared with controls. In older animals a 50% reduction in plaque number was achieved.
These structural changes were mirrored by functional improvements too, with treated mice recovering memory and cognitive abilities including being able to recall fearful stimuli, find their way around better and respond appropriately to smells.
The team think that bexarotene works by increasing the level of a substance called ApoE in the brain. This can dismantle the amyloid aggregates that are the neurological hallmark of the disease. Previous experiments in human subjects have shown that reducing the burden of these deposits can reduce the disease symptoms, suggesting that the agent might be able to achieve similar impacts in human subjects.