Posted on 05/17/2002 3:52:39 PM PDT by scouse
Drug saps Alzheimer's
Optimism for chemical that destabilizes harmful protein build-ups.
HELEN PEARSON
Clinical studies will start within weeks on a new drug that may erode the protein clumps behind Alzheimer's disease and type II diabetes.
In these diseases, proteins that are usually soluble fold abnormally into tightly packed deposits called amyloid that wreck internal organs. In mice, the prototype drug shrank these protein accretions within weeks, scientists have revealed. Preliminary tests on patients look promising.
"I can't describe how excited I was," says Mark Pepys of University College Medical School in London, who has been working on the idea for the past 25 years. "We've invented a new molecule - and it does what we want."
Leslie Iversen, who studies Alzheimer's at King's College London is also enthusiastic. Clearing away the plaques that clog patients' brains is thought to be key to reversing the nerve damage that causes dementia.
But Iversen suspects the drug will need some modification before it hits the shelf: "It's not a cure," he warns.
Blocker blocking
Pepys' drug targets a protein called serum amyloid P component or SAP. SAP coats amyloid deposits protecting them from being destroyed and removed by the body. "Normal scavenging mechanisms can't get rid of them," explains Iversen.
The team screened 100,000 chemicals for one that stops SAP sticking to amyloid. They developed a molecule that ties two SAP proteins together, which has the added bonus of speeding SAP breakdown in the liver1.
As the drug lowers SAP levels in the blood it strips away any SAP clinging to amyloid deposits. So while the drug cannot penetrate the brain, it can draw out the SAP lodged there and potentially destabilize Alzheimer's plaques.
The team gave the drug to 19 sufferers of systemic amyloidosis for up to nine and a half months. This rare and ultimately lethal condition is caused by widespread protein deposits affecting tissues such as skin and heart.
To watch SAP move around the body, they injected a radioactively labelled version of the protein which they followed with a whole-body radiation scanner.
Within ten minutes, SAP moved towards the liver. The drug cleared it from the blood after 24 hours. It is too early to say whether these gravely ill patients have improved, but Pepys' unpublished results suggest that amyloid build-ups are eroded.
Building on success
Vaccination against the amyloid protein - one of the most promising Alzheimer's treatment strategies being pursued - received a setback recently when clinical trials were halted because patients developed brain inflammation. Other drugs are being developed that prevent proteins massing into plaques.
But Pepys' molecule could tackle a wide range of diseases. Amyloid accumulates in the pancreas of people with type II, or adult onset, diabetes. People receiving kidney dialysis also suffer from build-up of proteins that dialysis machines cannot filter out.
In theory, the molecule might also alleviate prion diseases, including the human form of mad cow disease, variant Creutzfeldt-Jakob disease (vCJD), which is also caused by misfolded proteins. But amyloid deposits do not always form in these spongiform encephalopathies, so Pepys is cautious about whether the drug is appropriate to treat CJD.
What do you want to bet that the new molecule is a combination of nicotine and alchohol?
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