By Tony Fong
Fresh off its first commercial launches, molecular diagnostics company Satoris this week announced it has received a grant from the Michael J. Fox Foundation to investigate proteins associated with Parkinson's disease in the hopes of developing a diagnostic test for the disease.
The company, based in Menlo Park, Calif., is not releasing the terms of the grant, but Satoris CEO Cris McReynolds said that it will help cover the cost of conducting a single study to identify candidate protein biomarkers that may be indicative of Parkinson's.
As part of the study, its first targeting Parkinson's disease, Satoris researchers will use blood samples gathered by Bernard Ravina, an associate professor of neurology at the University of Rochester School of Medicine, to compare 500 proteins from 25 Parkinson's patients against 25 control samples. Ravina will not be doing any testing of the proteins, however.
While the list of proteins that will be interrogated include some that have been implicated in existing literature as being associated with Parkinson's, "by and large, it's a first look to see if anything lights up among this collection of proteins," McReynolds told ProteoMonitor this week. He added that the proteins were chosen because they are signaling proteins and may be more closely related biologically to the inherent underlying process of the disease.
To analyze the proteins, the researchers will use a modified form of RayBiotech's antibody-based quantitative nitrocellulose filter membrane array technology. RayBiotech and Satoris collaborated earlier this year to help launch Satoris' panels for Alzheimer's and dementia. RayBiotech, however, is not participating in the Parkinson's study.
The study is expected to start soon and to last less than one year, McReynolds said. If any candidate biomarkers are identified, Satoris will proceed with a larger clinical test to attempt to verify and validate them.
Signals to Parkinson's?
According to the Parkinson's Disease Foundation, Parkinson’s is estimated to afflict 4 million people worldwide. About 60,000 people in the US are diagnosed with the disease each year, it said.
Satoris was founded in 2003 with a focus on Alzheimer's disease. In May it launched its first commercial products: two assays for Alzheimer's and a broader assay for dementia.
While Parkinson's is sometimes viewed as a close cousin of Alzheimer's, commercially it has drawn comparatively less attention, and Satoris joins a small handful of companies actively developing a protein-based diagnostic for the disease. Other firms include Power3 Medical Products and Transgenomic, which are partnering on such a test; Arrayit; Amorfix Life Sciences; and Anteo Diagnostics.
One of the challenges of creating a protein test for Parkinson's — and of any neurodegenerative disease — has been specificity. Finding any biomarkers with diagnostic utility for any neurodegenerative disease has been elusive, but finding markers that can differentiate one neurodegenerative disease from another adds another layer of complexity to the task.
According to McReynolds, the differentiating aspect of Satoris' work is that it is based on signaling proteins, not proteins derived from a shotgun approach.
"The core hypothesis from our work in Alzheimer's was that there is communication across the blood-brain barrier of not only certain cell types but also cellular signaling communication factors or molecules that are associated with the communication of cells between themselves," he said. "The hypothesis is that these patterns of communications will be indicative of the disease process going on in the central nervous system, [and] the communication is something we can detect in the plasma."
In a statement announcing the Michael J. Fox Foundation funding, Satoris said that using the signaling-protein approach for its Alzheimer's work, it was able to simultaneously measure the abundance of 120 known plasma proteins that serve as "chemical messengers between blood cells, brain cells, and cells of the immune system."
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The levels of the proteins change in response to disease "and can be used as surrogate markers for measuring changes in disease progression and response to therapies," the company added.
Satoris’ three existing tests are available on a research-only basis; the two AD panels are based on biomarkers that were detected in research described in a 2007 Nature Medicine article. The research for both was done by a broad group of researchers that included those from Satoris [See PM 08/07/08].
The AD panels, called the Neuro62 Biomarker panel and the Neuro78 Biomarker panel, are based on the analysis of 3,300 patient samples and contain 62 and 78 protein biomarkers, respectively, that have been identified as being associated with the disease.
The Satoris Dementia Discrimination Panel, by comparison, comprises 12 proteins that the company said can help "clinical researchers in differentiating between patients suffering from Alzheimer's and patients suffering from other forms of dementia," Satoris said in a statement announcing the launch of the three panels.
The company is developing an Alzheimer's test specifically for non-symptomatic and early-symptomatic patients, McReynolds said.
Based on the results of its Alzheimer's work, Satoris is betting that a similar set of signaling proteins for Parkinson's exist. "And it was fortunate that [the Michael J. Fox Foundation] shared the concern and the belief that this approach was going to have some merits," McReynolds said.
The foundation did not respond to a request for comment.
Currently, physicians diagnose Parkinson's with a neurological evaluation, based on a patient's movement, coordination, speaking ability, balance, and medical history.
No diagnostic test exists, and instruments such as MRIs and CAT scans are unable to detect the disease because they are unable to pick up the chemical changes that occur in the brains of Parkinson's patients.
During the summer, though, the US Food and Drug Administration accepted a new drug application for DaTSCAN, a radiopharmaceutical that uses single photon emission computed tomography, or SPECT, imaging. Made by GE Healthcare, DaTSCAN has been available in Europe since 2000.
The FDA is considering GE's application under priority review. In its announcement, however, GE said that DaTSCAN has its limitations. For instance, it cannot discriminate Parkinson's from multiple system atrophy or progressive supranuclear palsy, for example, or Parkinson's disease dementia from probable Lewy body dementia.
In August, the FDA's Peripheral and Central Nervous System Drugs advisor committee, nonetheless, voted to recommend DaTSCAN to the FDA for approval.
If Satoris can develop a blood-based test for Parkinson's it could help to better manage treatment and monitor new therapies, McReynolds said. He added that in addition to identifying proteins indicative of the disease, Satoris hopes to find biomarkers that will allow for the stratification of the disease.
"If in this initial study and follow-up studies we do find that there are markers that seem to be present or in higher or lower concentrations than in normal sample, then I think we can begin to look at which might be associated with progression or indications of relative severity," he said, though those studies would be further down the line.