Alzheimer's drug may be tested on humans in 2 years

By Roger Highfield Scientists have devised a new drug to fight the most common form of dementia that could be tested on patients within two years. There are around three quarters of a million people in the UK with dementia and Alzheimer's is becoming increasingly common as the population ages. However, there are no effective treatments. Now a new way to fight the devastating disorder has emerged from devising a novel way to prevent what some scientists believe is the underlying cause, the build up of protein deposits in the brain, and in precisely the place where this damage occurs. The new drug was found to be effective when tested on fruit flies and mice that have been genetically engineered to develop the disease, showing that it could halve the harmful deposits in a few hours. Tests on humans are planned in around two years, after more testing on animals. Today, in the journal Science, the team of academics at the Max Plank Institute, Dresden, led by the company Jado Technologies, describes how the new approach has emerged from the discovery of a way to target an enzyme that is central to the build up of deposits in the brain of a protein called beta amyloid. The drug targets the membrane of brain cells, focusing on compartments in the membrane, called "rafts", that play a central role in many cellular processes. Although this drug is not the first to target the enzyme, called beta secretase, it is the first to do so in the right place, in the "intracellular membrane compartment" where the enzyme triggers the protein deposit build-ups. The team has devised a way to anchor the drug to the membrane to stop the harmful deposits. "Our data provide proof-of-principle of a new approach for directing small molecule inhibitors to disease causing raft targets in cellular membranes. In this instance, by directing inhibition to the sub-compartment where the enzyme is active, the approach has potential to be used in the design of more effective beta-secretase inhibitors for the treatment of Alzheimer's disease," noted Prof Kai Simons, Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, and co-founder of Jado. In tests on animals, the drug reduced beta-amyloid formation in the brain by 50 per cent over four hours, when targeted this way. However, when not targetted at the membrane the drug was ineffective. The key was using another molecule, called sterol, as the "anchor" for the enzyme inhibitor. Dr Lawrence Rajendran, first author, believes that this way of anchoring drugs to the cell membrane is a "proof-of-principle" for an approach that could be crucial for treating many other diseases too, such as Ebola and Aids. "It is like hitchhiking into the cell: We use cellular strategies to deliver the inhibitors to the exact site where they are needed - and maybe, one day, to combat Alzheimer's disease." "Routine animal studies have to be performed before we go to clinical trials," he says. "We expect that this might take about two years." "This seminal paper is the culmination of many years pioneering research by this team in the emerging field of raft intervention therapeutics. At Jado we have taken this approach to the next level and are building a pipeline of compounds targeting rafts for the treatment of allergic disorders and infectious diseases," says Charl van Zyl, CEO. Alzheimer's affects one in 20 of those over 65, causing loss of memory, personality changes and, eventually, death.