rBChE May Play A Neuroprotective Role In Alzheimer's Disease

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Scientists from the Hebrew University of Jerusalem, one of PharmAthene's collaboration partners, have recently obtained new data suggesting that recombinant butyrylcholinesterase (rBChE), a non-pegylated form of Protexia, may have neuroprotective benefits.

Recent research conducted by Dr. Hermona Soreq and co-workers at the Alexander Silberman Life Sciences Institute at The Hebrew University of Jerusalem, in collaboration with PharmAthene, examined the role of rBChE in the prevention of amyloid plaques, which are believed to play a role in the development of Alzheimer's disease.

"The role of amyloid plaques in the pathophysiology of Alzheimer's disease is well documented, and a number of approaches have been studied which attempt to block their formation by interfering at critical stages in this complex pathway," said Hermona Soreq, Ph.D., Professor of Molecular Biology and Dean of Sciences at The Hebrew University. "Our preliminary results are especially intriguing as they continue to suggest that rBChE is effective not only in inhibiting plaque formation, but also in potentially attenuating neurotoxicity. The accumulating data provide compelling evidence that rBChE may serve as a natural protector against amyloid toxicity. In view of the empirical evidence gathered to date, the role of rBChE in the pathogenesis of Alzheimer's disease merits closer scrutiny and understanding."

Recent in vitro data have demonstrated that rBChE effectively blocked the formation of amyloid fibrils, precursors to plaque formation in the brain. These data were substantiated by transmission electron microscopy studies, which showed that rBChE dramatically suppressed the formation of fibrils, resulting in thinner and less branched filaments than would normally occur in patients with Alzheimer's disease.

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More recent studies have also demonstrated that this plaque inhibitory activity is still active when peptide fragments of rBChE are used, rather than the full length protein. This may be an advantage in developing a product that can cross the blood brain barrier.

The formation of amyloid plaques in Alzheimer's disease is theorized to involve a structural transition of the amyloid beta peptide. New data generated by Dr. Soreq corroborate earlier findings, and demonstrate that both rBChE and its peptide fragments could disrupt amyloid beta organization and potentially limit its neurotoxicity.

David P. Wright, President and Chief Executive Officer of PharmAthene commented, "The early research is certainly intriguing. While we are still a long way from understanding the utility of rBChE in patients with Alzheimer's disease, our next steps will include studying rBChE in a transgenic mouse model of Alzheimer's disease to evaluate its ability to inhibit or reduce amyloid plaque formation. If the results continue to be encouraging, it may allow PharmAthene to expand applications of rBChE to additional areas beyond organophosphorous nerve agent toxicity with potentially important benefits to society. Importantly, this is consistent with our strategy of developing dual-use applications for our biodefense programs in other commercial markets."

Alzheimer's disease is a progressive neurodegenerative disease which is estimated to affect more than 4.5 million Americans. One of the hallmarks of Alzheimer's disease is the accumulation of excessive amyloid plaques in areas of the brain that control memory and cognition. Amyloid multimers are believed to be neurotoxic and interfere with the normal communication between neurons. A growing body of scientific evidence suggests that the accumulation of amyloid plaques and neurofibrillary tangles in the brain may play an important role in the development and progression of Alzheimer's disease.

The work conducted under the Alzheimer's research program is based on a patent owned by Yissum (the technology transfer company of The Hebrew University of Jerusalem), entitled "Human BChE Variants as Protectors from Amyloid Diseases", which has been licensed to PharmAthene.

As part of the collaboration with Hebrew University, PharmAthene has an exclusive, worldwide license to the application of rBChE and its corresponding peptides for use in the field of Alzheimer's disease.

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