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CPHPC, new hope for Alzheimer’s disease

Tuesday, April 14, 2009, 17:49 This news item was posted in Pharma category and has 0 Comments so far.

 

UK’s  Pentraxin and GlaxoSmithKline collaborate to develop CPHPC therapy for Alzheimer’s

CPHPC, a compound developed by the British researchers offers some hope for Alzheimer’s disease (dementia).

CPHPC or (R)-1-[6-[(R)-2-Carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC) is a small molecule drug which targets serum amyloid P component (SAP).

CPHPC is found to be effective for treatment of systemic amyloidosis, which is usually associated with Alzheimer’s disease.

The researchers at the University College London found the small molecule drug caused the disappearance of a protein called SAP, thought to be involved in the disease, from the brains of five Alzheimer’s patients who took it for three months.

The results were published in the journal Proceedings of the National Academy of Science.

Britain’s Alzheimer’s Research Trust, which helped fund the research, said the results with the drug, CPHPC, were cause for “cautious optimism,” but it was too soon to know for sure if removing SAP from the brain would provide clinical benefit.

Larger scale clinical studies are now planned.

The CPHPC approach targetting SAP was was devised by Professor Mark Pepys FRS of UCL. Later Prof Pepys developed CPHPC in collaboration with Roche in Basel, Switzerland.

Pentraxin Therapeutics Ltd, a UCL spin-off company, acquired the full rights to CPHPC, this year. Roche has agreed to fully divest its portfolio of patents on CPHPC and its ‘know-how’ on the compound, to allow Pentraxin to proceed with further development of CPHPC alone or in collaboration with other partners. Pentraxin is currently in discussions on partnering certain aspects of the programme and has plans for conducting its own trials with CPHPC in Alzheimer’s disease.

Prof. Pepys comments, “Following the Roche decision to halt the development of CPHPC because of internal reprioritisation, we are delighted to be able to progress the project ourselves. We have very promising clinical results with CPHPC in patients with systemic amyloidosis, and the combination of CPHPC with a specific antibody we have lately developed unprecedentedly clears amyloid deposits in experimental models of the disease.”

Now GlaxoSmithKline (GSK) has joined hands with Pentraxin to develop the world’s first dual drug–antibody treatment for the rare and often fatal condition amyloidosis.

With this new agreement, the research teams from UCL and GSK will work together to convert the mouse antibody into one that can be used in humans in combination with CPHPC. The aim is to find out if the benefits seen in the animal model can be replicated in patients with amyloidosis.

The collaboration brings together UCL’s clinical and science expertise and the development expertise of GSK’s Academic Discovery Performance and Biopharm Units.

“We are delighted to enter into this alliance,” said Mike Owen, Senior Vice-President of Biopharmaceutical Research at GSK. “Our biopharmaceutical and clinical development capabilities and Professor Pepys’s team’s knowledge of the disease provide a synergistic collaboration that will greatly enhance our chances of success.”

Pentraxin initially developed the small molecule drug CPHPC. Although early results were promising, it could not benefit patients in the advanced stages of the disease. “Something more dramatic was needed,” explained Professor Mark Pepys, the head of Pentraxin and the UCL Centre for Amyloidosis & Acute Phase Proteins, which includes the UK National Amyloidosis Centre. “We then combined CPHPC treatment with an antibody that seeks out the amyloid deposits in the organs in mice. This combination triggered a rapid clearance of the deposits.”

Amyloidosis is a disease caused by the build-up of abnormal proteins (amyloids) in body tissues, which leads to organ failure. The heart, kidneys, liver, and almost any other organ can be affected. Around 500 new cases are diagnosed each year in the UK, and – despite the fact that patients receive the best available therapy – the prognosis for patients is poor and new treatments are urgently needed.

Around 700,000 people are living with various forms of dementia throughout the UK and that number is set to double in the next generation.

“New treatments for Alzheimer’s disease are desperately needed, and it’s possible that this small molecule could be a future candidate,” said Trust Chief Executive Rebecca Wood.

Given the world’s ageing population and the lack of an effective treatment, new medicines for Alzheimer’s are seen as a major untapped opportunity for the pharmaceutical industry.

Among the furthest advanced experimental drugs for Azheimer’s is bapineuzumab from Elan and Wyeth — now being acquired by Pfizer — which produced disappointing clinical trial results.

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