Epsilon? wrote:The interesting thing to me is the reversal of plaques. This could be measurable on PET scan in humans....we would need a drug for humans that was both highly active and safe... If you could prescreen with PET, treat and repeat the PET you could establish an effect without enrolling thousands of subjects. If candidate drugs did not show an effect you could avoid long term large group testing. It is unclear if any of this will pan out.
Hi again, Epsilon?,
An effect of reversal of beta amyloid on PET scans or CSF in humans has already been established, at least on a short-term basis in several BACE-1 inhibitors. Here's a brief summary of the early results of two drugs which showed reductions in beta amyloid of from 63%-90%: JNJ 54861911 (Janssen division of Johnson& Johnson) and CNP520 (Novartis & others in partnership) http://www.alzheimersanddementia.com/article/S1552-5260(16)30653-7/pdf
Unfortunately, showing that these drugs dramatically reduce amyloid in the brain is only the "proof of concept" phase. Now they have to show that the drugs also affect one or more of several events or biomarker outcomes approved by the FDA recently as markers for a successful Alzheimer's drug. And they have to show evidence that these drugs would be safe at doses that would be effective if taken for possibly decades prior to the risk of onset of mild cognitive impairment. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf
Phase 2/3 Trials for both safety and efficacy are now underway and enrolling people (with slightly different risk parameters) in the Generations 1 and 2 studies and the EARLY study. Both are being done in both the U.S. and other countries.
Here's a link to the EARLY study with study locations noted: https://globaltrialfinder.janssen.com/trial/54861911ALZ2003
Here's a link to the Generations Study with locations noted: https://www.generationprogram.com/#Main
In spite of Merck's drug trial being ended, it appears that there is still considerable interest in the BACE-1 hypothesis.