The simplicity of MethylPlex testing overcomes the barriers of time and cost that have made cancer screening based on DNA methylation impractical until now.
"DNA methylation is potentially the most sensitive and specific indication for early cancer detection and prognosis," explains Dr. Vladimir Makarov, Founder and CSO of Rubicon Genomics. "MethylPlex is the key to unlocking this diagnostic potential because it produces high resolution maps of methylation for more than 10,000 genes in one day for less than $.10 per gene. This reduces the time and cost to discover and validate new markers by nearly 100- fold."
MethylPlex microarray profiling of genome methylation is as simple and inexpensive as the profiling of gene expression. Key markers for detecting two initial types of cancer, prostate and esophageal, will be determined by analyzing the methylation patterns from hundreds of patients.
Hospitals and reference laboratories will use inexpensive, non-invasive MethylPlex diagnostic tests. The first commercial tests will use serum or urine from patients with high PSA or other indications of prostate cancer to identify those cases that should be treated aggressively, preventing patients from having to undergo periodic biopsies or unnecessary surgeries.
In 2005 Rubicon will determine the specificity and sensitivity of the prostate test by using regulatory-grade clinical samples in preparation for an FDA filing. The automated MethylPlex tests will be inexpensive enough for primary diagnosis and frequent monitoring of disease progression.
MethylPlex has equal potential for diagnosis of other types of cancer.
Rubicon has discovered almost 1,000 new methylation sites associated with cancer; more than double the number discovered by other technologies in the past 10 years.
rubicongenomics/
After immunizing roughly 55 percent of the mouse population over the course of the two studies, researchers saw an overall reduction of 16 percent in the prevalence of nymphal infection at locations in which mice had been given vaccine versus placebo. This translates to a possible reduction of 27 percent in nymphal infection had all the mice been vaccinated.
In addition, the researchers concluded that other animals, such as chipmunks and shrews, may play a larger role in the spread of Lyme disease than was previously thought. For example, the researchers discovered that the success of the vaccine in curbing the infection of nymphal ticks depended largely on mouse density. In sites where mouse densities were high, the numbers of infected nymphs in corresponding control sites were also high, indicating the important role mice played in nymphal infection prevalence in those sites. It was in these areas where the vaccine worked best in preventing nymphal infection the following year. In contrast, where mouse densities were lower, the vaccine was less effective in reducing the prevalence of nymphal infection, suggesting that other animals probably played a role in disease transmission. Also, the researchers found that certain strains of B. burgdorferi were less likely than other strains to be passed from a mouse to a tick; these strains were most prevalent in nymphs in one study site in which infection prevalence did not change following mouse immunization, again indicating the contribution of other animal reservoirs.
Which animals help spread Lyme disease, and, more specifically, which ones transmit the more virulent strains, needs further study, the researchers contend, to determine how best to implement a broad-based vaccination program. Also, study sites need to be monitored for strains that are not susceptible to the vaccine. Lastly, experiments will be conducted in which the vaccine is administered orally--the most logical way to vaccinate large numbers of animals--either as food pellets or in bait boxes targeted to certain species, much like the rabies vaccination program that has met with success in the United States and Europe. Such a vaccination program would be environmentally beneficial, say the researchers, because it would not detrimentally affect the ecology of a region.
Other collaborators on the study include Durland Fish, Ph.D., Yale University School of Medicine, and Jean Tsao, Ph.D., Michigan State University (formerly with University of Chicago and Yale).
niaid.nih/