Adlyfe's (Rockville, Maryland) top executive believes that the company's technology to detect misfolded proteins in prion diseases has received "somewhat of a validation in the scientific community" through the August publication of a study in the journal Transfusion, a publication of the AABB, (formerly the American Association of Blood Banks; Bethesda, Maryland).

Alan Rudolph, PhD, CEO of Adlyfe, described the study as "good proof-of-principle" that the company's technology can "through [evaluation in] four species, including humans, measure these misfolded prion forms in the blood."

He told Diagnostics & Imaging Week: "What's really been a challenge for those of us in the diagnostic field in amyloid proteins associated with chronic brain diseases is to determine if blood or other peripheral compartments like cerebral spinal fluid can accurately correlate with events of these proteins in the brain."

Adlyfe says that its technology — a misfolded protein diagnostic — is based on the synthesis of conformationally sensitive peptides — or chains of amino acids that are smaller than proteins — which are created to target specific protein shapes associated with various diseases.

The interaction of the target protein with Adlyfe's peptides produces a conformational change that then converts to a fluorescent signal. Further amplification of the signal is generated as additional ligands undergo conformational changes.

That is the basis for the test's sensitivity and ability to detect very low amyloid protein levels before symptoms occur, according to the company.

But it says that the trick is to determine — by measuring those amyloid proteins in a particular form in the brain — if they can then be correlated with a disease that may be causing symptoms in the patient of transmissible spongiform encephalopathy (TSE) diseases in both animals and humans.

In animals, TSE is known as Mad Cow disease, but the human form of TSE is known as Creutzfeldt-Jakob disease.

Adlyfe said that scientists have tried to develop a preclinical diagnostic test for TSE since the discovery that humans with variant Creutzfeld-Jakob disease can transmit disease via blood transfusions. However, the prevalence of the sporadic form of Creutzfeldt-Jakob is not very common.

The company says that the coexistence of a large amount of protein in the normally folded shape, and the fact that misfolded proteins do not trigger an immune system response that would enable diagnosis based on the detection of antibodies, have made it difficult for companies to develop such a diagnostic.

And, unfortunately, the only way to detect Alzheimer's disease — primarily by finding the presence of amyloid plaques in the brain is via autopsy.

Now Adlyfe says it has the proof that it needs to show the ability of Adlyfe's Misfolded Protein Diagnostic (MPD) to detect the presence of misfolded proteins in brain, serum and plasma in a way that is both sensitive and specific. And Rudolph said the privately held company interested in partnering with another firm to push forward with studies of this diagnostic approach, particularly for Alzheimer's disease thus producing a huge breakthrough for the sector.

Founded in 2003, Adlyfe was initially funded by a group of governmental organizations: the Defense Advanced Research Projects Agency, the U.S. Army Medical Research and Materiel Command, the National Heart, Lung and Blood Institute of the National Institutes of Health, and the Department of Environment, Food and Rural Affairs in Great Britain.

At the time, these agencies primarily were concerned and focused on the transmission of Mad Cow disease between animals.

More recently, the company said that it has raised additional funding with Canaan Venture Partners and Burrill Associates.

Although there continue to be "issues around what is the market for prion tests like this," Rudolph said he believes that the peer-reviewed and "very well qualified" study would seem to support continued study of the tests — for animal care in addition to clinical diagnostics for humans.

For example, the only way to determine if Mad Cow disease exists in animals at the slaughterhouse is to test them after death. Rudolph said that the goal of such a test would be to test for Mad Cow with a blood test prior to death.

"The ability to detect to detect [Mad Cow] in the blood allows you to screen animals ante-mortem," Rudolph said. "It allows you to screen other bovine by-products in their final form."

He noted that there are plenty of these by-products that are commercially sold. And there are others in which humans are exposed to such by-products, such as bovine serum albumin for cell culture.

"So, the ability to detect in very small amounts of blood allows you to do a sort of on-the-hoof . . . test," he said.

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