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Drug targets the ties that bind in protein diseases

Updated:
Researchers have developed a drug intended to attack the clumps of proteins found in patients suffering from diseases such as Alzheimer's and adult-onset diabetes.

The international team hopes that experiments now under way will show that the drug, CPHPC, shrinks the clumps in people suffering from a rare disease called amyloidosis. The drug has already been shown to do so in laboratory mice.

Fewer than 1,000 people die of amyloidosis each year in the United States. But future clinical trials will focus on Alzheimer's, which afflicts about 4 million Americans.

In amyloidosis, abnormal proteins collect throughout the body, causing clumps that can wreak havoc with the normal function of many organs.

The clumps, called amyloid fibrils or plaque, are also a hallmark of such diseases as adult-onset diabetes and Alzheimer's. In Alzheimer's patients, these plaques clog the brain and are believed to cause the neurological damage that robs people of their memories.

It is the drug's potential application against Alzheimer's that has Mark Pepys and his study co-authors the most excited.

One expert, however, expressed skepticism that the drug would be effective against Alzheimer's.

CPHPC acts by targeting a protein called serum amyloid P component, or SAP, that binds the amyloid clumps together and makes them resistant to breakdown by the body.

Pepys and his colleagues showed that CPHPC, a nontoxic drug patented by Swiss pharmaceutical company F. Hoffmann-La Roche, lowered SAP levels in the blood of 19 patients suffering from amyloidosis. The results were published in Thursday's issue of the journal Nature.

``It completely, rapidly, dramatically, miraculously cleared the blood of the target protein,'' said Pepys, a professor of medicine at the Royal Free and University College Medical School in London. Tests also showed CPHPC drew down levels of SAP in the clumps.

Pepys cautioned that the team has yet to cure anybody of anything. But he said that if trials show CPHPC can shrink amyloid clumps, it could help fight the debilitating effects of Alzheimer's.

Sangram Sisodia, a professor of neuroscience at the University of Chicago, said it appears the drug would be efficient in tackling amyloidosis. But it is not clear whether it would work against Alzheimer's, he said.

Sisodia noted that experiments in mice have shown that amyloid clumps can form without SAP.
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