December 10, 2010 C2N Diagnostics co-founding scientist – Dr. Randall Bateman – and colleagues at Washington University School of Medicine publish key findings in online edition of Science
ST. LOUIS, MO – C2N Diagnostics announced today that one of its co-founding scientists, Dr. Randall Bateman, and his colleagues from the Washington University School of Medicine have independently authored an article that appeared in yesterday’s online edition of Science. The publication, entitled “Decreased Clearance of CNS Amyloid-b in Alzheimer’s Disease”, sheds important new light into the potential origins of late-onset, or sporadic, Alzheimer’s Disease (AD). The findings may also aid in the future development of an early diagnostic test and target for effective drug therapy.
Amyloid-beta (Ab) is a protein fragment found in plaques within the brains of individuals with dementia due to AD. It is believed that excessive levels of Ab are toxic to brain cells and a potential key mediator of AD progression. Historically, the reasons for the accumulation of Ab plaques in patients with sporadic AD have been poorly understood. A common presumption is that AD may result from an over-production of the protein fragment.
The new study provides an important piece of evidence that AD may result from a defect in the clearance, or removal, of Ab from the brain rather than from its over-production. Dr. Bateman and his colleagues used the stable-isotope labeling kinetics (SILK) assay platform currently commercialized by C2N and licensed from Washington University, to measure the production and clearance rates of the Ab marker isolated from the cerebrospinal fluid (CSF) of 24 individuals. Study subjects fell into one of two groups: those with late-onset, symptomatic AD, and those who were cognitively normal, but of comparable age. The mean age of the individuals tested was 74 years.
Individuals with late-onset AD had no impairment in their production rate of Ab. Strikingly, however, these individuals on average had an approximate 30% lower clearance rate relative to those who were cognitively normal. The results achieved statistical significance, implying that the findings were very unlikely due to a chance observation. Per the authors, these data suggest that “Ab clearance mechanisms may be critically important in the development of AD.” Based on the magnitude of the observed clearance defect, the authors also suggested that “brain Ab accumulates over approximately 10 years” before the time of onset of the symptoms of AD.
Stated Dr. Joel Braunstein, managing member of C2N, “We are very proud of Dr. Bateman and his colleagues for their important contributions to the field. Hopefully, the findings from this study will advance the research community’s efforts to develop agents that will modify the underlying biology of AD, while potentially creating an opportunity for earlier disease detection through the use of effective biomarkers. Early intervention is likely to afford the greatest clinical benefit to patients at high risk for symptomatic AD.”
Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ. Decreased clearance of CNS amyloid-beta in Alzheimer's disease. Science Express, Dec. 9, 2010. http://www.sciencemag.org/content/early/2010/12/08/science.1197623
About Alzheimer’s Disease
Alzheimer’s disease is a progressive neurological disorder characterized by loss of memory and decline in basic mental ability. Though several drugs are available to treat the symptoms of Alzheimer’s, none halt or modify disease progression. The risk of developing Alzheimer’s disease increases significantly with age. By the age of 85, approximately 1 out of 2 people likely have the disease. Alzheimer’s disease affects more than 20 million elderly people worldwide, and the incidence is likely to grow rapidly over the following decades. According to the Alzheimer’s Research Trust, an estimated 4.6 million new cases of Alzheimer’s are diagnosed each year worldwide, and roughly 500,000 of these occur in the United States alone.
About C2N Diagnostics
C2N Diagnostics, LLC formed in late 2007 by scientific co-founders Drs. David Holtzman and Randall Bateman of Washington University School of Medicine in St. Louis, the Washington University Office of Technology Management, and LifeTech Research, a Maryland-based technology research and commercialization firm (www.lifetechresearch.com). C2N resides at the Center for Emerging Technologies in St. Louis. The company is developing a suite of biomarker assays and tools to assist in pre-clinical drug discovery, clinical drug development, and the early detection and assessment of progression of debilitating neurodegenerative disorders. The SILK-Aß™ assay, relies on stable isotope labeling and tandem mass spectrometry for the precise measurement of the kinetics, or in vivo metabolism, of amyloid-beta – a small peptide implicated as a key mediator of Alzheimer’s disease. Other products are in development to target Parkinson’s disease, Huntington’s disease, schizophrenia, and amyotrophic lateral sclerosis (ALS), among others. For additional information, see www.c2ndiagnostics.com or call 1-877-C2N-DIAG (1-877-226-3424).