Research finds potential for Alzheimer’s therapy

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cavalierdaily.com

by Amanda Gellet, Senior Writer

Clinical trial results, published in The Journal of Neuroscienceby Eli Lilly & Co., suggest a promising new therapy for Alzheimer’s disease.

The BACE1 inhibitor drug called LY2811376 prevents beta-secretase 1 from producing amyloid-beta, a protein fragment commonly associated with Alzheimer’s.

Researchers considered BACE1 inhibition to be a potential therapy for more than a decade, but Eli Lilly & Co.’s findings marked the first successful pharmaceutical reduction of amyloid-beta levels in humans.

In Alzheimer’s patients, amyloid-beta collects in the brain and becomes pathogenic. This excess leads to extreme memory loss, severe problems with daily activities and eventually death, said Matt Seward, a University Ph.D. student who studies Alzheimer’s disease.

During Phase I, Eli Lilly & Co. found LY2811376 lowered the levels of amyloid-beta in blood plasma and cerebrospinal fluid — the fluid surrounding the brain. The inhibitor proved more successful than other current drugs at lowering amyloid-beta levels in healthy volunteers.

This drug does not reverse the damage already caused to the brains of Alzheimer patients. Since the brain is not able to regenerate itself, Seward said a drug must be found which alters amyloid-beta levels in seemingly healthy individuals to successfully delay or prevent disease progression. The success of LY2811376 in Phase I studies suggests this drug could offer a viable solution.

Testing on pre-clinical animals demonstrated the potential side effects of long-term exposure to LY2811376, including the collection of granules in the eyes and some parts of the brain. The retina cells of the animals’ eyes became enlarged because of the number of granules which had collected in the cells. Moreover, there was evidence of degeneration in the eye. Phase I participants did not experience significant side effects.

Alzheimer’s disease accounts for 60 to 80 percent of all dementia and is the sixth-leading cause of death in the United States, according to the Alzheimer’s Association.

The number of Alzheimer’s-related deaths rose 66 percent between 2000 and 2008, reflecting the aging of the United States’ baby-boomer generation. This number is expected to continue to increase as the population becomes even older. Experts predict that by 2050 Alzheimer’s care will cost Medicare and Medicaid $800 billion annually, surpassing the country’s current military budget.

Of the top-10 causes of death in the United States, Alzheimer’s is the only disease without a treatment which prevents, cures or slows its progression.

Current therapies for Alzheimer’s only treat the symptoms of the disease. A drug such as LY2811376, which is directed at the disease itself, may represent a huge leap forward for Alzheimer’s treatment, Seward said.

Eli Lilly & Co.’s research also helped the medical community understand the principles directing the disease, he added.

“The success of LY2811376 is that it shows proof of principle,” Seward said