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Newest approach to “Plaque Busters”
By Joel Ross | September 9, 2010
There has been a huge amount of coverage on Alzheimer’s Disease with the NY Times writer, Gina Kolata covering a huge amount of topics which will be address on subsequent posts so stay tuned readers.
Lilly recently had a terrible set back as did the many patients enrolled in their study testing what is known as a “gamma secretase inhibitor”. The treated AD patients fared worse than those given a placebo and those taking their compound had higher rates of skin cancer. A big blow for Lilly indeed and makes all other pharmaceutical companies look even harder for that “magic bullet” to remove toxic plaque or slow or even prevent its production.
New Alzheimer’s approach may sidestep early snags
3:35pm EDT
* Compounds alter but do not block gamma secretase
* Neurogenic Pharmaceuticals hopes to do human trials
By Julie Steenhuysen
CHICAGO, Sept 8 (Reuters) – A new Alzheimer’s compound kept toxic clumps from forming in the brains of mice, without causing side effects seen in similar drugs, U.S. researchers said on Wednesday.
They said the drug changes the way an enzyme called gamma secretase works, without completely blocking it, an approach that so far has failed in human trials.
Instead, the new compound just tinkers with the machinery a bit, said Steven Wagner, a neuroscientist at the University of California, San Diego School of Medicine who led the research published in the journal Neuron.
“We can tweak it,” Wagner said in a telephone interview.
Several companies, including Eli Lilly (LLY.N: Quote, Profile, Research, Stock Buzz), have been developing gamma secretase blockers in hopes of warding off brain-damaging clumps of a protein called beta amyloid, which kill brain cells and wipe out thinking and memory in people with Alzheimer’s disease.
But gamma secretase also plays an important role in everyday cell function.
The trick was to find a way to keep the bad proteins from forming without interfering with other essential brain functions, Wagner said.
The team screened thousands of molecules looking for one that would modify the enzyme in just the right way.
They tested several of these in genetically engineered mice that develop Alzheimer’s-related brain plaques.
One chemical, compound 4, kept brain plaques from forming, but left other brain processes alone.
The results were so promising at reducing levels of the protein that a private San Diego-based company called Neurogenetic Pharmaceuticals Inc has licensed the patent. The company has dubbed it NGP 555.
“It is something they are ultimately going to try to test in humans,” Wagner said.
The hope is to avoid problems seen with similar drugs, such as Lilly’s failed drug semagacestat, which tried to broadly knock down the activity of the enzyme.
Patients enrolled in Eli Lilly’s late-stage study of semagacestat actually had their brain function get worse, and some developed a form of skin cancer.
“Our approach is to target and inhibit only the production of key peptides that may play a pivotal role in the pathogenesis of Alzheimer’s disease,” Wagner said in a statement.
More than 5 million Americans have Alzheimer’s disease — more than 26 million people worldwide.
Current drugs only treat symptoms, but no drug arrests the steady mental decline that robs victims of the ability to think and care for themselves. (Editing by Jerry Norton)
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