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Amprion Wins NIH Grant to Develop Alzheimer's Disease Diagnostic


NEW YORK (GenomeWeb) – Diagnostics firm Amprion this month received a one-year grant from the National Institutes of Health to develop a blood-based Alzheimer's disease diagnostic based on a technology originally developed for prion amplification.

Called protein misfolding cyclic amplification (PMCA), the technique was invented by University of Texas researcher and Amprion Co-founder Claudio Soto. As he described in a 2012 publication, PMCA involves incubating materials containing minute amounts of infectious prions with an excess of normal prion protein, then boosting the conversion by cycles of sonication to fragment the converting units. The result is accelerated prion replication.

Amprion and Soto have conducted a number of studies using PMCA to detect the misfolded prions associated with Creutzfeldt-Jakob disease (CJD), most recently reporting on its use to detect prions responsible for the human form of the disease in the urine of patients.

According to Amprion Co-founder and CEO Russ Lebovitz, the company is currently in discussions with US and European regulators about starting, potentially as soon as this summer, a study that will evaluate PMCA in positive and negative CJD blood samples, laying the groundwork for regulatory clearance.

Seeing potential for the technology beyond prions, the company has also begun exploring its diagnostic use in other neurodegenerative disorders, beginning with Alzheimer's disease.

Like prion diseases, Alzheimer's disease is characterized by the accumulation of misfolded proteins, namely amyloid-beta, which results in senile plaques. Given this similarity, and because these misfolded proteins form soluble particles that escape the brain into circulation, Lebovitz said, Amprion believes the PMCA technology can be modified to amplify and detect misfolded amyloid-beta, as well.

He said that the firm has already generated data showing that the approach can be used to detect soluble misfolded amyloid-beta in the cerebrospinal fluid (CSF) of Alzheimer's disease patients. With the NIH grant, worth $223,574, Amprion is aiming to refine the PMCA technology so that it can detect similar misfolded amyloid-beta in blood.

"The issue … is that blood is a much more complex matrix" than CSF, Lebovitz noted. "There are a lot of proteins in the blood that [could interfere with the sensitivity and specificity of] the assay."

Amprion has come up with several methods to overcome this issue, and part of the grant money will be used to demonstrate that these work without impacting the test's sensitivity and specificity.

The grant will also be used to see how the test performs in clinically validated blood samples of Alzheimer's disease patients and normal controls, he added. Should this effort prove successful, Amprion plans to move into a larger study to generate the data needed to secure regulatory approval.

While Amprion views the assay as a tool for diagnosing patients with Alzheimer's disease, the company also expects it to be useful for monitoring patient response to treatment given that it provides a quantitative measurement of amyloid-beta levels.

"It's not only a yes/no," Lebovitz said. "There are quantitative nuances that we think could … help choose which drug for which patient and really help drug development. If you know something is not working in a given patient, then why continue?"

Amprion also has an earlier-stage effort underway in Parkinson's disease, which is focused on amplifying and detecting soluble misfolded alpha-synuclein particles, he noted. Although the protein's role in the disease isn't fully understood, it is believed that an aberrant soluble conformation is responsible for the disorder.

As with its CJD and Alzheimer's disease programs, Amprion anticipates obtaining NIH funding to support the Parkinson's disease effort, Lebovitz said.

He noted that the firm has largely relied on government grants to fund its research and development, and that it has thus far limited its venture capital fundraising to roughly $500,000, since it only "makes sense to raise VC money when you are ready to scale." And that, he added, won't happen until the company has identified a path to market for its CJD test based on discussions with regulators.