Saturday, January 12, 2013

Clinical Trials Update (including CPHPC)

This post will give a little update on the CPHPC trial being done at the National Amyloidosis Centre (NAC) in London, and I'll also discuss a trial being done in the US that is relevant for fibrinogen amyloidosis.

But first, if you'd like to meet me or Mom in person, all you have to do is come to the Chicago area in October. We'll be there for the familial amyloidosis meeting October 25 - 27. Details can be found here: I think there were around 175 attendees at the 2011 meeting, and the 2013 meeting already has about 100 people planning on attending.

Back to the clinical trials. This past October, Nicola Lloyd (formerly of South Africa) informed me that she made it to London and has begun the CPHPC treatments, which consist of three daily injections. Hopefully she can report some good results to us within a year. In her email she included some information provided by the NAC about CPHPC and how it functions, some of which I have copied below. Be sure to read the final paragraph, in bold. (Warning: British spelling ahead):

Amyloidosis is due to the accumulation of abnormal protein fibres (amyloid fibrils) in vital organs and various tissues throughout the body. SAP (serum amyloid P component) is a normal blood protein of unknown function that binds to amyloid fibrils, and helps to stabilise them, contributing to progression of the disease. It has been shown that SAP helps to prevent the breakdown of amyloid fibrils, and mice that do not have SAP are relatively resistant to developing amyloidosis in the first place. No ill effects have been attributed to the life long lack of SAP in these mice.
CPHPC is a drug that is given daily by subcutaneous injection 2 or 3 times a day. It is absorbed into the bloodstream where it binds selectively to pairs of SAP molecules, which are then recognised by the liver to be abnormal and are removed from the blood. CPHPC treatment thus depletes the blood of SAP protein and, in turn, SAP that has accumulated in the amyloidotic organs gradually diminishes. The hope is that removal of SAP from amyloid will result in the body clearing away amyloid more quickly and efficiently, although this has not yet been proven in man.
In hereditary renal amyloidosis, which is inexorably progressive, the amount of healthy protein being lost into the urine fell in four out of five patients receiving CPHPC, and kidney function was prolonged compared to a historical group of such patients.

So there we have a not-too-technical description of what CPHPC does in conjuction with SAP. The initial study of CPHPC in 31 human patients can be found here. Since there were fibrinogen amyloidosis patients included in that study, it is listed on the resources page of this blog under March of 2010. (Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis)


The CPHPC trial is a great opportunity for people living over there in Jolly Olde England, but are there any drug trials available over here in the good ol' US of A? As a matter of fact, there is one. Boston University is currently recruiting participants for a trial on doxycycline. Doxy who? "Doxy cycling," but change the "g" to an "e". Here is a link to the information about the trial:

Here is a link to a short abstract about doxycycline presented at the American Society of Hematology annual meeting in December of 2012:

And here is my attempt at a non-technical one-paragraph summary of what this is all about:

AL amyloidosis (primary) is often treated by having patients undergo a stem cell transplant. (The other main treatment option is chemotherapy.) Patients are given antibiotics after a stem cell transplant, with penicillin being the number one choice. But patients who are allergic to penicillin are typically given doxycycline instead. The Mayo Clinic reviewed the records of 455 patients who received stem cell transplants between 1996 and 2011, and found that those who received doxycline tended to survive longer than those who received penicillin. Couple that information with some other data indicating that doxycycline can disrupt the formation of amyloid fibrils, and now that's something worth studying further.

The description of the doxycycline clinical trial on the web site doesn't specifically mention fibrinogen amyloidosis, but it does mention ATTR. So I wrote to the contact person listed and asked if a person who was diagnosed with fibrinogen amyloidosis, confirmed by kidney biopsy, but still in the early stages of the disease would qualify. Dr. Berk at Boston wrote me back and said yes. He also said he would not recommend the drug to someone who had tested positive for the genetic mutation but did not yet have any symptoms.

As far as I know this is the first clinical trial in the US with something for fibrinogen amyloidosis patients. Up until now the only treatment options were organ transplants (liver, kidney, or both). Unfortunately Mom's kidneys have progressed to the point where she is not eligible for the trial. I am currently asymptomatic so I am not eligible either. (Maybe there will be a preventive medication for fibrinogen amyloidosis someday.)

The existence of these clinical trials does underscore the importance of genetic testing and early detection. It would be a shame for someone to be diagnosed so late in the progression of the disease that the window of opportunity for participating in a clinical trial is closed. So if you're having trouble convincing family members of the importance of genetic testing and regularly having their creatinine and proteinuria checked, let them know that there may be treatment options other than organ transplants, but that window can close up quickly.


  1. Thanks for the info. Have their been anymore clinical studies involving CPHPC since the 2010 study? My wife has Al cardiac amyloidosis and is presently in remission>

    Pete Wirth

    1. Pete, the 2010 study is the only published one involving CPHPC I am aware of, but there are patients (like Nicola) participating now in another study of CPHPC effectiveness being done by the National Amyloidosis Centre in London. It's not really a clinical trial, per se, because it's not a double-blind study.

      I couldn't find anything about this current study with a quick search of the NAC web site (, so anyone interested would probably need to contact the NAC to find out more. Unfortunately I don't think we'll be seeing CPHPC in the US any time soon unless a major pharmaceutical company gets involved.

    2. David - Thanks for the reply. I wonder how we get this more traction in the states? is a good web site for posting scientific studies. They have a health section. We need to get the research community on amyloidosis to get their material to a wider audience.