While proteomics holds promise as a technology that could potentially help in the early diagnosis of Alzheimer’s disease, no one has yet been able to translate proteins into a predictive tool for the debilitating ailment.
But a small molecular diagnostics firm, Satoris, is trying to change that and this week, its chief executive told ProteoMonitor its protein-based Alzheimer’s test may be ready to hit the market by the end of the year.
The company is currently collaborating with the Mayo Clinic to validate results from a study published late last year. The validation work is expected to be completed in September, and depending on the results, it could clear the way for Satoris to hit the market with two Alzheimer’s protein panels within the next few months, said Cris McReynolds, president and CEO of Satoris.
Both panels are based on work published
in the fall in Nature Medicine
, in which researchers, including those from Satoris, found 18 proteins associated with Alzheimer’s.
In that study, researchers looked at 259 archived blood samples ranging from patients who had no symptoms to those who had advanced Alzheimer’s. The resulting 18-protein panel had both sensitivity and specificity of about 90 percent and was able to “pick out the Alzheimer’s from a population of dementia and to properly identify those who had AD,” according to McReynolds.
Authors of the study also said that the panel was able to identify patients with mild cognitive impairment who eventually were diagnosed with Alzheimer’s two to six years later, but McReynolds said it is not clear whether that means the panel is predictive of the disease or that it is only “able to detect the early disease process associated with AD.” Though mild cognitive impairment is believed to be a possible precursor to Alzheimer’s, some patients with it do not develop Alzheimer’s.
Satoris, based in Redwood City, Calif., is preparing to do another validation study to clarify the panel’s predictive ability “because we think that’s such an important question,” said Lynn Kozma, development director for the firm. The study is expected to start in the fall.
In the current validation study being conducted with the Mayo Clinic, researchers are retrospectively and prospectively analyzing about 500 samples collected from nine centers in the US and Europe. No data was yet available, McReynolds said.
As part of that work, Satoris is also taking the panel, which was developed using an antibody filter array, and converting it into a test to be used on a Luminex platform, McReynolds said. And while the original panel comprised 18 proteins, the objective is to reduce that number.
“There’s always a cost and complexity advantage to be realized [based on] the fewer analytes you have to work with,” he said.
“The theory here is that they’re a little bit closer biologically to the inherent underlying process of the disease.”
If results from the validation study are positive, the company would proceed to make it and a broader panel of biomarkers for Alzheimer’s disease to be available on a research-use basis only through Rule-Based Medicine, an Austin, Texas-based biomarker-testing laboratory with which Satoris is partnering to bring a test to market.
The broader panel is based on 45 proteins that “showed significantly different behavior in a population of AD patients versus other classes,” McReynolds said. Less specific for Alzheimer’s, the panel would be more appropriate in discovery work or drug development where a researcher is “looking for markers that might specifically correlate with response observed in the application of a particular therapy or drug,” he said.
The two panels are complementary, and which panel would be used would depend on the researcher’s goals, McReynolds said. “If a drug company is simply interested in detecting AD in a population of patients [for example, for enrollment in a clinical trial], it would use the AD detection panel, he said. “However, if it wanted to identify specific markers that corresponded with observed response, with their specific treatment, in a trial, they might interrogate with the larger panel.
For now, the goal is to make the Alzheimer’s diagnostic available for research laboratories, but ultimately, Satoris plans to bring it into the clinical setting, which would require approval by the US Food and Drug Administration. That remains a far-off goal, McReynolds said, but for a disease in which diagnosis is a tricky proposition, such a tool could be an important aid to doctors.
According to the Alzheimer’s Association, an estimated 5.2 million Americans have the disease. But because diagnosis is part science and part guesswork, only about 60 percent of patients with the disease will be accurately diagnosed, according to Satoris.
A number of proteomics studies are directed at the disease, but to date none has produced results translating into a protein-based diagnostic test for Alzheimer’s. A number of companies are in the early stages of developing such a tool, including Protagen, Digilab Biovision, Caprion Proteomics, and Power3 Medical Products.
Power3 Medical Products is perhaps the furthest along in the development pipeline [See PM 11/30/2006
]. The company is expected to complete a 300-patient clinical-validation study next month and could have its Alzheimer’s test, called NuroPro, commercially available by the end of this year or early 2009, Chairman and CEO Steve Rash told ProteoMonitor
NuroPro, which has 95-percent specificity and sensitivity, is, like Satoris’ panel, blood-based. Based on 59 biomarkers, Power3 is in the midst of bringing that number down. Unlike Satoris, however, Power3 wants to immediately market it as a lab-based test for clinicians.
“If you whittle it down, that makes it much more feasible for doing a high-throughput immunoassay-based test, like an ELISA,” Rash said. “And that’s eventually what we’re going to do. We’re going to introduce it as a [2D-gel-based test], which is a lower throughput, and then simultaneously begin working on the ELISA test.”
According to McReynolds, a distinguishing aspect of Satoris’ Alzheimer panel is that it is based on signaling proteins, “so we’re not taking as broad of a shotgun approach as some other groups.”
“The theory here is that they’re a little bit closer biologically to the inherent underlying process of the disease,” Kozma added.
Founded in 2003, Satoris currently has no products on the market, and McReynolds was brought in last fall, in part, to help guide the company as it readies itself to launch the Alzheimer’s panel, he said.
He replaced Patrick Lynn, a co-founder of the company, who is now its executive chairman.
Prior to joining Satoris, McReynolds had been vice president of the molecular diagnostics business unit of Affymetrix and did consulting work for Satoris. “Bringing me in, I think, was identified as one of the steps necessary to continue our march toward commercialization,” he said.
In December, the company completed a Series B financing that raised $5.2 million and anticipates doing another round toward the end of the year, McReynolds said. Investors in the company are made up mainly of high-net-worth individuals, an angel fund, and the Brain Trust Accelerator Fund, a venture capital firm that was brought in during Satoris’ Series B round.
The company bills itself as a molecular neural diagnostic company, but while it currently is “ruthlessly focused on AD,” it may extend its reach during the coming months, McReynolds said. Its researchers have found discriminatory patterns in its protein panels with multiple sclerosis, Huntington’s disease, and Parkinson’s disease, and “what we see next is beginning to test sample populations from academic centers that are focused on studying those diseases,” he said.