Medical Device Daily

While controversy continues to surround how U.S. authorities are responding to a Texas cow found to have “mad cow” disease in June, Adlyfe (Rockville, Maryland) is continuing on a course begun in 2003 to develop tests for testing cattle, blood screening and possibly for a clinical diagnostic for protein-folding diseases.

The danger for humans from cows with mad cow disease is that people who eat the meat of an infected cow can develop the human form of the brain-wasting disease known as Creutzfeldt-Jacob disease. Although there have been confirmed cases of people in the UK contracting the disease through blood transfusions, still there is no way to screen blood or test cattle without first killing them and examining their brain tissue. Mad cow is a neurological disease.

Adlyfe hopes to change that and has received about $6 million in federal funding from the National Institutes of Health (NIH; Bethesda, Maryland) and the Defense Advanced Research Projects Agency (DARPA), Adlyfe CEO Alan Rudolph told Medical Device Daily. However, not all of it has been devoted to prion diseases.

“This originated with DARPA and NIH, and it actually had its origins in DARPA’s interest in threats to biosecurity, because in the cattle case, it’s only a few animals [that would have to be affected before one could see] large consequences to agro-economics, such as the closing of export markets,” Rudolph said. “So, it was in that spirit in which DARPA’s interest in the technology was motivated toward providing security against emerging threats.”

The company said new results from the test would be published in the Journal of Peptides. It also said that it has demonstrated detection of prion diseases in brain tissue and blood of cattle, sheep and humans in clinical laboratory sampling. The form of the brain-wasting disease in sheep is called sheep scrapie.

The test that is being developed to provide earlier diagnosis of mad cow disease was developed by Cindy Orser, vice president of research and development at Adlyfe.

Rudolph said that prions “certainly are an area that’s not well understood.”

“It’s an unusual paradigm for an infectious disease, because although controversial, the disease is [contracted] by the passing of a protein rather than a genomic content, such as bacterial or viral agents,” he said. “There’s still some controversy in the scientific community about whether there’s a genomic component of the passing of prion diseases.”

Adlyfe’s technology uses memetics, or peptides, for “looking for shape changes in proteins,” according to Rudolph. “Prion disease is story of protein-folding or shape change from a native conformation to a misfolded form,” he said. “We’re really addressing a new area called bioconformatics, which is really what can you learn from shape changes and conformational changes in molecules like proteins.”

Adlyfe has created “small pieces of these proteins” that can track shape change, Rudolph said. The small peptide, or memetic, is fluorescence-based – that is, it has fluorescent tags engineered onto it that look at the folding changes in proteins, he said. The test undergoes similar folding reactions to the target protein that Adlyfe is looking for and “transduces this color change or fluorescent signal” when there’s a positive finding.

“It’s a fairly simple, but elegant, innovative concept that we’ve reduced to practice in tracking protein folding and shape changes within protein aggregates that are correlated to these diseases,” he said.

In addition to the test for mad cow disease, Adlyfe is developing a blood-screening test for humans with a test called BSE-pronucleon. The company said the test provides results in 30 minutes, and because of its sensitivity, it also will have application to bovine byproducts such as gelatin, serum albumin and fetal calf serum. Those are products with human applications such as pharmaceuticals, cell-based therapeutics and cosmetics, meaning that they are regulated by the FDA.

Rudolph said Adlyfe is just beginning its discussions with the FDA. The difficulty, he said, is that there are no other tests for these diseases and, therefore, there is no regulatory policy or standards in place for such tests. So, predicting a timeframe for approaching the FDA or UK regulatory bodies is difficult until such standards have been established. Still, the company already is in discussions with potential partners for commercializing the tests.

“The notion that the FDA would look at a test like ours for testing raw materials or materials such as those derived from bovine byproducts, we believe is a viable direction for a test like ours,” Rudolph said.

He added that the regulatory environment around the U.S. Department of Agriculture and its handling of mad cow disease remains “cloudy.”

Adlyfe also is developing a blood test based on the same technology for Alzheimer’s disease, called Azpronucleon. The test targets the amyloid-b protein, the protein that aggregates in the brain with Alzheimer’s.

In addition to the U.S., the UK and European regulatory environment is a “very strong market pull for us, and clearly the CE marking . . . is an important one for us.”

And while these are the concerns for the company today, Rudolph said he expects to find other uses for the company’s technology down the road.

“We’re very hopeful in looking forward that our technology and our concepts and our intellectual property will address a category of diseases in which this folding or shape change is important,” he said.

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