George Fink, director of The Mental Health Research Institute of Victoria (Australia), announced today that a drug developed at the Institute shows promise as a therapy for Alzheimer’s disease.
The drug, PBT2, induces a rapid and dramatic reduction in amyloid A-beta in a mouse model; the mice exhibit improved cognitive performance in as little as four days after treatment begins. Trials in human patients are slated to begin very soon: in Sweden within a month or two, and in Australia in early 2007.
The mainstream-media articles on this story don’t say much about the mechanism of PBT2, but I gleaned this from the MHRI web site:
In collaboration with Prana Biotechnology, Kevin Barnham and Joe
Ciccotosto are focusing on the metal binding sites on the Aß amyloid,
as these provide a defined molecular target for a class of compounds
called MPACs (metal-protein attenuating compounds). These drugs
are now being tested in early stage clinical trials by Craig Ritchie,
Ashley Bush and collaborators, and encouraging results have been
From this and a little poking around about MPACs, I surmise that the mechanism involves making amyloid A-beta a more suitable target for native metalloproteases.
I had never heard of Prana Biotechnology, which has a delightfully kooky reference to preserving the “life force” of Alzheimer’s sufferers on their corporate web page. They’ve apparently been in the anti-Alzheimer’s business for a while; at least, long enough to have developed and tested another compound, PBT1 (clioquinol), as well.
In conjunction with exciting news about the use of passive immunization (administration of antibodies, rather than raising them inside the patient by administering an antigen) against amyloid, also announced at the 10th International Conference on Alzheimer’s Disease in Madrid, this news indicates that the next decade will see a revolution in the way that Alzheimer’s disease is treated clinically. Rather than merely forestalling the symptoms of cognitive decline, the new generation of drugs will attack the root cause of the disease. Furthermore, anti-amyloid therapies have the potential to be used preventively, rather than after symptoms have already manifested.