Possible Alzheimer's Disease Therapy Falters in Lab

Therapy targeting amyloid formation held interest for treating other neurological diseases as well

WEDNESDAY, Jan. 30 (HealthDay News) -- New findings on the behavior of amyloid inhibitors -- considered possible therapeutic candidates for diseases such as Alzheimer's and Huntington's -- cast doubt on their usefulness. The research was published online Jan. 27 in the journal Nature Chemical Biology.

Brian Y. Feng, Ph.D., of the University of California San Francisco (UCSF), and colleagues investigated whether chemical aggregates have the ability to impair the formation of amyloid fiber, since their ability to sequester enzymes might also allow them to keep protein molecules away from each other, thus preventing amyloid polymerization.

The authors of the study explain that the drugs did not function as they expected. Instead of preventing amyloid plaques, the drugs aggregated into clumps that then failed to cross the blood brain barrier. The drugs also failed to show any target specificity.

Once these drugs aggregate into clumps, "they no longer have the right pharmacology, they won't cross the [brain's] membrane barriers, and they inhibit everything -- any protein will bind with them," said senior author Brian Shoichet, Ph.D., professor of pharmaceutical chemistry at UCSF.

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