SAN FRANCISCO—Amarantus BioScience Holdings Inc. has announced positive top-line results of its LP-002 study of the Lymphocyte Proliferation Test (LymPro Test) blood diagnostic for Alzheimer’s disease (AD). The 140-subject study successfully demonstrated that multiple individual biomarkers achieved statistically significant results in correctly distinguishing patients with AD from healthy controls.
“Not only is LymPro a consistent and reliable tool in diagnosing Alzheimer’s disease, having completed ‘fit-for-purpose’ assay validation at Icon [which provides lab testing and biomarker services], it may now be used to enrich inclusion criteria in pharmaceutical clinical studies,” said Colin Bier, chief development officer of Amarantus Diagnostics. Biomarker services using LymPro data will be available for investigational use only in pharmaceutical therapeutic clinical development programs.
“LymPro represents an innovative approach to improving the diagnosis of Alzheimer’s disease by measuring a fundamental aspect of disease biology,” said Gerald E. Commissiong, president and CEO of Amarantus. “The fact that LymPro has the ability to distinguish patients with early-stage AD from control subjects will be important to the pharmaceutical industry engaged in Alzheimer’s research.”
The LymPro study evaluated 71 patients with mild-to-severe AD along with a control group of 69 healthy subjects. Each stage of Alzheimer’s disease showed significant differences in CD69 marker expression on subpopulations of lymphocytic cells as compared to healthy controls. CD69 is a protein expressed when lymphocytic blood cells undergo proliferation. Low levels of CD69 under cell division conditions suggest lymphocytic cell cycle dysregulation and a surrogate marker for the neuronal cell cycle dysregulation observed in the brains of AD patients during autopsy.
The expression of the marker CD69 was significantly lower in the AD patients, as measured under two different mitogenic stimulation conditions (LymPro Version 1 and LymPro Version 2). The LymPro Version 1 assay confirmed previous published work, particularly with the CD19+ positive lymphocytes.
After further analysis of a 44-subject, seven-year longitudinal retrospective study including patient record clinical data assessment over time, LymPro was able to differentiate Alzheimer’s disease from Parkinson’s and vascular dementias with a sensitivity of 94 percent and specificity of 65 percent. This finding is important, as it could assist pharmaceutical companies in distinguishing dementia of the Alzheimer’s type from dementia of a disparate etiology. Amarantus hopes to publish data in peer-reviewed journals as well as present the studies at various scientific congresses throughout 2015.
Amarantus has also identified a new, undisclosed biomarker that correlates with AD diagnosis in the LP-002 study. This new marker could become a component of a multivariate algorithm (LymPro Score) which will create a simplified assessment of a person’s probability of having Alzheimer’s disease. Commissiong tells DDNews, “The newly identified biomarker will impact the sensitivity of the assay and possibly improve the specificity of the test’s diagnostic capabilities. Amarantus may be presenting data in March at the ADPD conference in Nice, France.”
Amarantus has also announced its first Alzheimer’s biomarker services collaboration with Anavex Life Sciences Corp. The investigational Alzheimer’s drug candidate ANAVEX 2-73 and drug combination ANAVEX PLUS will be used to evaluate the pharmacodynamic effect on biomarker CD69 in specific subpopulations of peripheral blood lymphocytes, using the LymPro diagnostic. LymPro is not the only test for Alzheimer’s currently in development, but Commissiong believes LymPro has an advantage in that it does not only identify people with Alzheimer’s. Lympro is a dynamic assay, which may potentially assist in the development of therapeutic drugs for Alzheimer’s patients.
“This is the type of collaboration that becomes possible with new diagnostic tools to help therapeutic interventions in AD. The mechanisms involved may begin to validate emerging targets in the field of AD, and I am excited to help bring this collaboration forward,” commented Dr. Robert A. Stern, director of the Clinical Core of the Boston University Alzheimer’s Disease Center, director of clinical research for the CTE Center at Boston University and member of Amarantus Diagnostics’ scientific advisory board.
ANAVEX 2-73 is an orally available small molecule being investigated for AD treatment. ANAVEX 2-73 has preclinical data indicating there is potential for the drug to be able to prevent, halt and/or reverse the course of Alzheimer’s. The combined therapeutic ANAVEX 2-73 and donepezil (Aricept), called ANAVEX PLUS, has a promising synergistic effect; ANAVEX PLUS produced up to 80 percent greater reversal of memory loss in Alzheimer’s than individual usage of donepezil or ANAVEX 2-73.
“We are pleased to assist Anavex, our first customer, in evaluating the potential of ANAVEX 2-73 and ANAVEX PLUS to increase CD69 expression using LymPro in blood derived from AD patients,” said Commissiong. “Based on data generated in two previous peer-reviewed publications, our recently completed LP-002 clinical study, as well as studies presented by Amarantus in 2014 at the Alzheimer Association International Conference, CD69 expression as measured by LymPro is decreased in patients with AD, as compared to healthy controls and patients with confounding dementias. The ability of a new drug candidate to increase CD69 expression, as measured by LymPro, may be indicative of a modification in the fundamental Alzheimer’s disease process known as cell cycle dysregulation.”