Medical Device Daily

Adlyfe (Rockville, Maryland) this week reported that it has secured a U.S. patent for its technology covering a method for the early detection of more than 40 amyloid diseases. The company’s goal is to utilize this method as a platform for a diagnostic test for Alzheimer’s disease (AD) within the next two to three years.

Founded in 2003, the company originally had focused on a test for another disease involving misfolded proteins, Creutzfeldt-Jacob disease, or the human version of what is known as “Mad Cow” disease.

However, CEO Alan Rudolph, PhD, told Medical Device Daily that the company “shifted its focus to Alzheimer’s as the target” because, “undoubtedly, the diseases that are listed in the patent announcement today are significantly more prevalent than the prion diseases in the UK.”

Proteins are said to spontaneously “fold” into their particular conformation as a result of their surrounding cellular environment but “misfold” or fold incorrectly as a result of incorrect hydrophobic interactions.

Rudolph described the new patent, titled “Misfolded Protein Sensor Method in Body Fluids,” as “really the anchor of our portfolio — that is, it’s the earliest and broadest claim that really speak to the unique method of detection for these amyloid proteins and amyloid diseases.”

In addition to AD, which will be the initial target, among those 40 amyloid diseases are Parkinson’s disease, Huntington’s disease, systemic amyloidosis, diabetes, certain cardiovascular diseases, as well as the original target, Creutzfeldt-Jakob disease.

For AD, the expectation is that early diagnosis — in a disease area where the only definitive diagnosis comes at autopsy — will lead to earlier therapeutic interventions. Such a test may also play an important role “in future clinical trials of therapeutic candidates for these diseases by quantifiying the presence or absence” of misfolded amyloid proteins and potentially evaluating drug efficacy and dosing, the company said.

Ultimately, Adlyfe hopes to develop a diagnostic test “panel” to test for AD and certain of the other diseases that are thought to be the result of the aggregation of amyloid plaques in the brain, which leads to dementia.

Rudolph said that there are some 4 million to 5 million cases of AD now in the U.S., with about 100,000 deaths each year.

“The prevalence projections are growing,” Rudolph said, not only in the U.S., but also in Europe, where Adlyfe first hopes to secure a CE mark and later seek FDA approval.

The company describes the technology as a “catalytic detection method” that screens for very low concentrations of misfolded particles, such as proteins in serum or blood, which could identify asymptomatic patients.

“Back when the patent was filed, it wasn’t catalytic in the strict sense of how a chemist or biochemist would use the word catalytic, but it’s really a very similar thing,” Cindy Orser, PhD, told MDD. Orser is Adlyfe’s VP of R&D and one of the three inventors of the technology.

“The reason we chose that word is because there are really two phenomenons occurring; one is the target peptide recognizing its substrate, a folded prion protein, or the misfolded aggregated protein,” she said.

Subsequent to that, it becomes what she characterized as a “domino effect,” whereby signaling through those peptide molecules that have interacted with a misfolded protein, will then itself misfold. “Then that’s propagated throughout the population of those peptide molecules that are in the reaction assay,” she said, or what is otherwise known as “amplification.”

Rudolph said these so-called “propagation catalysts” are formally called Pronucleon ligands.

“That is really what is unique about technology — it’s that we’re using the same molecule to interact with the target and to propagate this signal with molecules resulting in an amplified signal which is generated by the fluorophores that are on the end of the peptides,” Orser told MDD. “When the propagation catalyst changes, when it interacts with its substrate, the probes or fluorophores come into proximity with each other and you actually see a visual shift in fluorescence.”

In other efforts toward a diagnostic test for Alzheimer’s, scientists at the Blanchette Rockefeller Neurosciences Institute (BRNI; Morgantown, West Virginia), affiliated with West Virginia University (also Morgantown), reported last August that they have isolated a substance in skin cells that may provide doctors with a quick and accurate yes-or-no answer when they suspect a patient is showing early signs of the disease. They hope this puts them on the road toward developing a skin test for Alzheimer’s disease as well as the road to personalized medicine.

Adlyfe was initially funded by the Defense Advanced Research Projects Agency (DARPA; Ft. Detrick, Maryland) of the U.S. Department of Defense, with more than $7 million from that agency, in addition to the U.S. Army Medical Research and Materiel Command, the National Heart, Lung and Blood Institute, and the UK’s Department for Environment, Food and Rural Affairs (MDD, July 13, 2005). It also had received about $650,000 in a two-year grant from the UK Department of Environment, Food and Rural Affairs in September 2005 for a sensitive early blood test for animal prion diseases (Medical Device Daily, Sept. 8, 2005).

The shift to Alzheimer’s occurred when the company received its most recent financing of $3.3 million from venture capital firms Canaan Venture Partners and Burrill Associates.