October 2010 - CPHPC update

While we wait for my genetic testing results (again), I thought I'd go off on a slight tangent, back up just a bit, and mention something called CPHPC. What is CPHPC, you ask? Well, CPHPC is R-1-[6-[R-2-Carboxy-Pyrrolidin-1-yl]-6-oxo-Hexanoyl] Pyrrolidine-2-Carboxylic acid. I don't know why they felt a need to shorten all that to "CPHPC," but I guess I'll go along with it.

Ok, so what does CPHPC have to do with amyloidosis? Here is the grossly oversimplified answer to that question: CPHPC may enable the human body to eliminate amyloid deposits. Yes, you read that right. CPHPC may enable the human body to eliminate amyloid deposits. But before you jump up and down declaring CPHPC to be the wonder drug that cures amyloidosis, be aware that this drug has a loooooooong history, and as of the end of 2010 had only been used on laboratory mice, not humans. [Edit: There was a study on the effects of CPHPC in 31 human patients between 2001 and 2006. Here is the link to that article: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.08036.x/full] It was developed in the UK, and I remember hearing one of the US doctors say that the amyloidosis medical community has been hearing about CPHPC for so long that they're sort of tired of hearing about it, and they'd rather not hear about it again unless there are some results from use in humans.

I'm bringing up CPHPC now because in November of 2010 someone on the amyloidosis Listserv (not the Yahoo support group) mentioned an October 2010 article about CPHPC that appeared in Financial Times. It gives a good, concise summary of the history of CPHPC. Here's the link to the article: http://www.ft.com/intl/cms/s/2/eb4f6f88-e169-11df-90b7-00144feabdc0.html#axzz2CFGywJS9

And here is the text of the article. Note the link to Alzheimer's, and support from a major pharmaceutical company:

After 35 years spent studying the protein amyloid, Mark Pepys, professor of medicine at University College London, is finding persistence pays off.

For 35 years, Pepys has been studying amyloid, an insoluble protein that can cause serious disease when excessive amounts build up in the body.

And now, a paper published last week in the top journal Nature showed that a drug that he designed in the 1990s, called CPHPC, works well in combination with a newly designed antibody to clear amyloid deposits in laboratory mice.

A trial in patients will follow soon. If that succeeds too, the immediate clinical benefits will go to sufferers of an incurable disease called systemic amyloidosis, which causes organ failure in tens of thousands of people worldwide.

Amyloidosis, which affects about one person in 1,000, results from the build-up of abnormal fibres in the body. In the case of Alzheimer’s, amyloid deposits contribute to the destruction of the brain.

The original breakthrough came in the 1980s when Pepys realised that a normal blood protein called serum amyloid P component or SAP was the key to tackling amyloidosis.

SAP is always present in amyloid deposits as well as in the blood, and it contributes to the formation and persistence of amyloid.

In collaboration with Roche, the Swiss drug company, he developed CPHPC, a drug that targets SAP and removes it from the blood. This treatment stopped further accumulation of amyloid but did not lead to clearance of existing deposits, perhaps because it did not remove all the SAP from the amyloid.

Roche then pulled out of the collaboration but Pepys wasn’t discouraged. Nor was the Medical Research Council, which has funded his work from the start.

He had the idea of combining CPHPC with an antibody to target the residual SAP – and he persuaded another pharmaceutical giant, GlaxoSmithKline, to work on its development.

“Our findings open up promising prospects for successful intervention in patients,” said Professor Pepys.

=====

An obvious question to ask, given the title of this blog, is whether or not CPHPC is expected to work on reducing all types of amyloid deposits, or just those found in cases of AL (primary) amyloidosis. My understanding from one of the doctors at one of the support group meetings is that CPHPC is expected to work on all types. He gave a technical explanation on why that was the case, and I believe it has something to do with the fact that the serum amyloid P (SAP) is always present and binds to the amyloid deposits. Since the SAP is being targeted and cleared out of the body, it takes along whatever it is attached to. That's totally from memory, so I could be all wrong.

There are a lot of articles about CPHPC out there, so if you want to find out more just search for these terms: CPHPC, Pepys, SAP, amyloidosis. You'll likely find some articles published later than 2010 to be interesting. CPHPC might even get mentioned again in this blog.  ;-)

Ok, where were we? Oh yeah, waiting on my genetic testing results from Boston.

[Edited December 24, 2012]