The research published today in Neuron is on the success of gamma secretase modulator (GSM) drugs in Alzheimer’s disease mice from Steve Wagner and Rudy Tanzi.
Tanzi writes that the GSMs “could be used like statins are used today to prevent heart disease. If there was pre-symptomatic evidence that amyloid levels were too high in a patient’s brain, a GSM might be taken to lower relevant peptide levels and reduce AD risk. You don’t want to knock out these peptides. They have a purpose. You just want to dial them back to safe levels.”
Wagner says “We’ve shown that a compound can modulate enzyme activity without completely shutting down the enzyme. We think we’ve opened up a new area of drug discovery for pharmaceutical companies and universities. We hope they will pursue some of these compounds to see if they can be used in people.”
Cure Alzheimer’s Fund is supporting the development of novel GSM's, independent of those presented in the paper.
The Cell paper published last week describes the normal role of the beta amyloid precursor protein (APP) and strongly supports the Prana Biotechnology drug (PBT2) approach that was first developed in Rudy Tanzi’s lab. Tanzi is a Prana co-founder and is co-author on the paper.
Sam Gandy, M.D Ph.D, Mount Sinai School of Medicine, New York, described this report, as “providing a major advance in deciphering the underlying causes of Alzheimer’s disease while at the same time pointing us toward a new and exciting strategy for treating or preventing the disease with a drug such as PBT2, which affects brain metals”.
The evidence published in Cell shows that the source of beta-amyloid, APP, plays a hitherto unknown critical role in exporting iron out of neurons. If APP fails to carry out this role, iron builds up in the neurons contributing to oxidative stress, neurofibrillary tangle formation and ultimately neuronal cell death.