Amarantus BioScience Holdings, Inc. recently released promising results from the Lymphocyte Proliferation Test (LymPro Test®) blood diagnostic for Alzheimer’s disease (AD) LP-002 study. Amarantus is a biotechnology company focused on research and development of treatments and diagnostics for diseases related to neurodegenerative and apoptosis (programmed cell death) processes that contribute to Alzheimer’s disease, Parkinson’s disease, and ophthalmological disorders. In this study, the LymPro Test® enabled researchers to correctly distinguish patients with moderate-to-severe AD from healthy controls with statistically significant results. Following these positive results,Amarantus will address the potential use of LymPros in diagnosing early-stage AD patients.
Alzheimer’s disease (AD) is characterized by progressive loss of memory and other cognitive functions. In the United States, Alzheimer’s is the third leading cause of death, and it is estimated that more than 5.4 million people have the disease. More than 500,000 patients are diagnosed per year, where one-in-eight older Americans are affected by the disease. Alzheimer’s disease inflicts an enormous emotional and financial burden on patients, their families, and society. Alzheimer’s costs in the United States are expected to exceed $1.4 trillion in 2050. In Alzheimer’s disease, as well as in some other diseases, it is hypothesized that there is an aberrant cell cycle re-entry by neurons.
The Lymphocyte Proliferation Test (LymPro Test®) is a diagnostic blood test that measures the ability of peripheral blood lymphocytes to respond to an external mitogenic stimulation that induces them to enter the cell cycle. LymPro is unique in the use of peripheral blood lymphocytes (PBLs) as a surrogate for neuronal cell function, suggesting a common immune-based relationship between PBLs and neurons in the brain.
The LP-002 study had 72 subjects, including 36 patients with moderate-to-severe Alzheimer’s disease (AD) and a control group of 36 healthy subjects. In the study, the expression of the marker CD69, a protein expressed when lymphocytic blood cells are proliferating and is an early marker of cell division, was assessed. The expression of the marker CD69 on specific sub-populations of lymphocytic cells was statistically significantly lower in the AD groups than in the control group, when measured with two different conditions of stimulation (LymPro Version 1 and LymPro Version 2). In AD patients, the lower expression levels of CD69 suggests cell cycle dysregulation of lymphocytes and is a surrogate marker for the neuronal cell cycle dysregulation, which has been observed in the brains of AD patients in autopsies. A potential link between cell cycle dysregulation, amyloid beta plaque,s and tau tangles has been suggested in AD.
The range of variations observed in sensitivity and specificity between LymPro Version 1 and LymPro Version 2 are common in diagnostic testing in heterogeneous indications such as Alzheimer’s. Further, the expression of CD69 did not change with disease severity, which is consistent with previous work, suggesting that LymPro is measuring a fundamental stage-independent biology in AD patients.
Following these encouraging results, the company is planning to expand the inclusion criteria to include patients diagnosed with mild Alzheimer’s disease. This study will enroll 68 additional subjects, including 34 mild-to-severe Alzheimer’s patients and 34 healthy controls. Amarantus predicts completing this enrollment in the fourth quarter of 2014, and will announce data from an in-depth analysis from the full cohort of 140 subjects (72 patients + 68 patient extension) shortly thereafter.
Amarantus is confident that the results from both Version 1 and Version 2 of LymPro are suitable for commercialization and in the validating of both versions for use in the Research Use Only (RUO) market. Amarantus plans to launch LymPro for RUO in the fourth quarter of 2014, mainly targeting pharmaceutical clinical trials. The company does not require Clinical Laboratory Improvement Amendments (CLIA) certification to launch LymPro in the RUO market.
“LymPro will have great utility to the pharmaceutical companies developing drugs for Alzheimer’s disease, as it will permit a more reliable way of selecting subjects for inclusion in trials, thereby assuring an enriched population and mitigating the risk of including non-Alzheimer’s disease subjects,” said Colin Bier, PhD, member of the Amarantus Board of Advisors who is tasked with the development of LymPro, in the Amarantus press release.
“Amarantus is aiming to be first to market with an accurate, reliable and commercially-viable diagnostic blood test for Alzheimer’s disease,” said Gerald E. Commissiong in the Amarantus press release.
“Today’s data gives us all the information we need to move full steam ahead with this strategy. We can now tailor our initial marketing efforts towards the $150M RUO market, primarily targeting pharmaceutical companies engaged in Alzheimer’s disease therapeutic trials. We have nearly completed assembling the resources needed to launch LymPro to the RUO community in the fourth quarter. Thereafter, we intend to market LymPro to the broader medical community, initially under CLIA. We estimate the worldwide market for an Alzheimer’s diagnostic is $3B” concluded Gerald E. Commissiong.