Skip to main content
Premium Trial:

Request an Annual Quote

Caprion Collaborating With FNIH to Test Alzheimer's Protein Panel


NEW YORK (GenomeWeb) – Caprion Bioscience is investigating whether a five-protein panel can be useful in early detection and predicting progression in Alzheimer's disease.

The company said this week that it has entered in a collaboration with the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium to measures proteins in its CNS ProteoCarta MRM biomarker panel in longitudinally collected samples from some 200 subjects from the Alzheimer's Disease Neuroimaging initiative.

The project follows a previous collaboration between Caprion and the FNIH in which the company developed a multiple-reaction monitoring mass spec assay measuring 142 proteins in cerebrospinal fluid that has been linked to Alzheimer's disease. Published in a 2015 study in the journal Proteomics – Clinical Applications, the effort began with 222 proteins selected as candidates via literature review, and researchers arrived at the final set of 142 after discarding those proteins to which Caprion and its collaborators were not able to develop high-quality MRM assays.

Of these 142, five proteins showed particular promise for distinguishing between Alzheimer's patients and healthy controls, said Martin LeBlanc, Caprion's president and CEO. One of the main goals of the recently announced collaboration will be to test whether these proteins could help with earlier detection of Alzheimer's disease as well as with predicting patients likely to progress from mild cognitive impairment (MCI) to Alzheimer's.

"These proteins had stronger predictive value for separating normal versus AD, but they also had in combination with other known markers, like tau and beta-amyloid (Aβ), very good predictive value  predicting progression from MCI to Alzheimer's," LeBlanc said.

Caprion will convert the initial MRM assays developed for these five proteins from relative quantitation assays to absolute quantitation assays using heavy labeled peptide standards. They will then use those assays to measure levels of the markers in a cohort of around 200 subjects consisting of healthy controls, MCI patients, and Alzheimer's cases, assessing the protein levels at two to three time points per patient over the course of three years.

Markers for early detection and predicting progression in Alzheimer's are of key interest, particularly among pharma companies developing drugs for the disease. The industry has had little success to date in Alzheimer's therapeutics and one line of thinking holds that these struggles are due in part to treating patients too late in the disease process.

"The whole idea is that … some medications would be much more useful the earlier you intervene," LeBlanc said. "And, unfortunately, for a lack of these biomarkers we tend to perhaps intervene later on when the symptoms are manifest, because we don't have a very useful way to track the progression or the early detection of AD."

The other area where these markers hold potential is in tracking improvements due to treatment, LeBlanc said.

"If you can actually see there is a correlation with [biomarkers and] disease progression, you might be able to establish correlations with a drug that in a Phase II trial starts to reverse some of those proteins back towards a more healthy stage," he said. "So, to be able to have markers that would monitor efficacy of drugs against disease is also something that is lacking, because it takes an awful long time to be able to detect that at a symptomatic level."

Caprion and its collaborators will also measure an additional 150 or so proteins via MRM, though with relative rather than the absolute quantitation used in the five-marker subset, and these measurements could also provide useful data from drug development, LeBlanc said.

All [150] were selected because of their relevance to Alzheimer's, so it's hoped that you might develop some interesting pharmacodynamic markers [from this set]," he said, adding that researchers might also be able to gain "insights into the mechanism of action, or confirmation of certain mechanistic phenomena if certain proteins start to go up or down based on the interaction with the drug."

The collaboration's roster of participants, which includes the pharma firms Genentech, Janssen, Lundbeck, Merck, and Takeda, is indicative of the drug industry's interest in such markers.

Caprion is one of a number of companies and research groups that have pursued either CSF or blood-based protein markers for early detection or progression of Alzheimer's, but currently tau and Aβ remain the only protein markers commonly used in clinical and clinical trial work.

LeBlanc said he expects the five proteins being tested in the new stage of the collaboration would likely prove most useful in combination with more established measures like tau, Aβ, and clinical and imaging data.

"I think it's really by combining additional proteins with tau and Aβ and mental exams and imaging that you will ultimately make headway," he said.

"Of course, this is our first independent verification of the data [from the 2015 study]," he added. "It's the first time we're doing it on a longitudinal set of samples. So, we'll know more about how this can be deployed clinically after these experiments are completed."

Caprion has offered MRM-based measurements of the 142 CNS-related proteins detailed in the Proteomics – Clinical Applications study since it launched its CNS ProteoCarta panel in 2014. In addition to Alzheimer's-linked proteins, the company has added assays to proteins linked to other neurodegenerative diseases like Parkison's, LeBlanc said, adding that it has seen steady demand from the panel from drug companies working in this area.

"We've seen quite a bit of interest in this [panel]," he said. "People, for instance, are using it in their mouse models of Alzheimer's disease or preclinical studies of a compound to see what proteins are being impacted. It's an interesting way to, for not that much money, track quite a few proteins in multiplex and get a sense of what's going on."