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Results from a Initial Clinical Trial of CPHPC to Treat Systemic Amyloidosis

Results were recently published for the first trial of CPHPC as a therapy to clear out age-related deposits of the type of amyloid formed from misfolded transthyretin, normally responsible for transporting the thyroid hormone thyroxine in blood and cerebrospinal fluid. Amyloids are one of the distinguishing features of older tissues, and clearing them will be one of the necessary outcomes produced by any comprehensive suite of rejuvenation therapies developed in the near future.

The accumulation of transthyretin amyloid creates a condition known as senile systemic amyloidosis where it occurs to varying degrees for everyone in later life, and TTR amyloidosis when it arises in young people due to inherited mutations. Senile systemic amyloidosis is known to be responsible for a sizable fraction of deaths in supercentenarians, as the amyloid deposits clog the cardiovascular system to the point of failure. This process is also thought to play an underappreciated role in heart failure in the younger old demographic, however, and is involved in other age-related degenerative conditions such as spinal stenosis.

CPHPC works in an indirect way: it attacks an unfortunate aspect of our biochemistry that prevents existing clearance systems from getting rid of transthyretin amyloid. Serum amyloid P component (SAP) binds to amyloids such as misfolded transthyretin and blocks the normal mechanisms of clearance. Removing SAP led to clearance of amyloid, but the action of CPHPC wasn't good enough on its own. The trial combined CPHPC with an antibody also aimed at removing SAP from the picture, as the two together produced far better results in pre-trial studies.

At present there are few good treatments for amyloidosis, and those that do exist are fairly specific to narrow demographics and circumstances. CPHPC is one of a number of potentially broad and effective treatments somewhere in the development process, however, so we have cause to be fairly optimistic about the near future in this field. Some of these potential treatments have been helped along in their early stages by the SENS Research Foundation; take a look back in the Fight Aging! archives at the development of catabolic antibodies for TTR amyloidosis for example. In the case of CPHPC the trial results been a long time in the making: development of CPHPC as a therapy for systemic amyloidosis started more than a decade ago, and the deal to set up a clinical trial was struck back in 2009. The wheels of medical science move very slowly indeed. Still, the news is good by the sound of it:

Potential new approach to the treatment of systemic amyloidosis

In 2009 GSK and Pentraxin Therapeutics Ltd entered into collaboration to develop the world's first dual drug-antibody treatment for the rare disease systemic amyloidosis. The results of the first in human clinical trial have today been published. The publication shows the results of the first 15 patients treated with a therapeutic partnership of CPHPC (a small chemical molecule) and an anti-SAP antibody.

Amyloid is an abnormal protein material that accumulates in the tissues, damaging their structure and function and causing a rare and usually fatal disease called amyloidosis. Present treatments can stabilise some patients and substantially prolong life but about 20% of patients still die within 6 months of diagnosis. The results of the phase I study showed that the antibody was generally well tolerated and produced rapid clearance of amyloid from various organs. Removal of amyloid from the liver was associated with improved function. Whole body anterior amyloid scans of a patient with systemic amyloidosis show abundant amyloid in the liver before treatment and the almost complete absence of amyloid after a single dose of the new anti-SAP antibody.

Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component

We conducted an open-label, single-dose-escalation, phase 1 trial involving 15 patients with systemic amyloidosis. After first using CPHPC to deplete circulating SAP, we infused a fully humanized monoclonal IgG1 anti-SAP antibody. Patients with clinical evidence of cardiac involvement were not included for safety reasons. Organ function, inflammatory markers, and amyloid load were monitored.

There were no serious adverse events. Infusion reactions occurred in some of the initial recipients of larger doses of antibody; reactions were reduced by slowing the infusion rate for later patients. At 6 weeks, patients who had received a sufficient dose of antibody in relation to their amyloid load had decreased liver stiffness, as measured with the use of transient elastography. These patients also had improvements in liver function in association with a substantial reduction in hepatic amyloid load, as shown by means of SAP scintigraphy and measurement of extracellular volume by magnetic resonance imaging. A reduction in kidney amyloid load and shrinkage of an amyloid-laden lymph node were also observed.

Comments

An actual therapy for amyloids, possibly including the supercentenarian-slaying senile systemic amyloidosis.

If someone reaches the ripe old age of (a mere) 120 with the help of this stuff, pretty much everything on this site is going to get a whole lot more interest due to the whole "It's possible, it's actually possible" effect.

Posted by: Slicer at September 23rd, 2015 8:03 PM

That's neat. Combine this treatment with Seolytica and SC-treamtments.
We may already have serious anti aging therapies for those willing to risk it.

Posted by: arren at September 24th, 2015 12:41 AM

This and yesterday's grown kidney seem like unusually good progress to me.

Posted by: ale at September 24th, 2015 3:35 AM

My husband is suffering from wild type TTR. Are there any trials available?

Posted by: Becky Koffman at December 9th, 2015 7:37 PM

@Becky Koffman: The easiest place to find out is clinicaltrials.gov. E.g.:

https://clinicaltrials.gov/ct2/results?term=transthyretin&Search=Search

Beyond that the best source of information is always the researchers themselves, as they will know what is going on in their field and what is coming up. This is an age of communication and their email addresses are not hard to find if you know names and research institutions; just read the publicity materials and then go and look at the staff web pages.

Posted by: Reason at December 9th, 2015 7:59 PM

so is this already an available therapy and why not if you mention the results were positive?

Posted by: mane at July 17th, 2017 5:06 AM

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