|
Page 15 |
|
Prof. Jim Patrick: Department of Neuroscience, Baylor College of Medicine, Houston, Texas
"I retired on June 1, 2007. Through the BSF collaboration, I played a major role in developing the transgenic mouse lines that were transferred to the HU, and participated, together with Prof. De Biasi, in Dr. Broidie’s Post-Doctoral training."
Prof. Mariella De Biasi: Department of Neuroscience, Baylor College of Medicine, Houston, Texas
"I am now actively collaborating with Prof. Soreq in studying mice expressing human acetylcholinesterase variants. Her laboratory probes the mechanisms whereby nicotinic acetylcholine receptors affect brain function in health and disease. We share interest in the role of the cholinergic system in AD (Alzheimer’s Disease): in the early stages and in the severity of the symptoms, which correlate with progressive loss of cholinergic neurons and neuronal nicotinic receptors function/expression in specific brain regions."
Interference with normal communication between neurons in brain areas controlling memory and cognition by amyloid plaque (AP) (which consists of insoluble β-amyloid (β-A) polypeptide aggregates) is characteristic of AD (Alzheimer’s Disease) and progressive NDD (neurodegenerative disease). The cholinergic nerve cells (expressing the cholinesterase (ChE) family of enzymes, which is responsible for breaking down the acetylcholine neurotransmitter) are sensitive under these conditions and die prematurely.
Prof. Soreq did a great deal of pioneering work in which she cloned and engineered the genes coding for the ChEs. She also identified rBChE, a natural protector against degenerative brain damage and toxic nerve agents (see below). Broadening the commercial application of this new approach by two companies, one in Israel and the other in the United States, is expected to bring important benefits to society in the future.
Cooperation In this BSF collaboration, Profs. De Biasi and Patrick sent transgenic mice produced at BCM to Prof. Soreq’s laboratory. These transgenic engineering techniques allow large-scale production of human ChE in goats
Findings In in vitro experiments, Prof. Soreq recently found that rBChE (recombinant butyrl-cholinesterase), produced from the milk of transgenic goats, interferes with the critical stages of AP formation There are fewer, thinner and less branched protein fibrils in cultures incubated with rBChE (as indicated by transmission electron microscopy). Thus, rBChE seems to be a natural protector against degenerative brain damage, suggesting possible clinical use for this engineered protein.
The Hebrew University’s Yissum technology transfer company holds the license for therapeutic approaches based on this technology for NDD. Pharmathene Ltd, a leading United States bio-defense company specializing in countermeasures against chemical and biological terrorism, is evaluating another commercial form of rBChE, known as Protexia, for preventing and treating damage by toxic nerve agents. This company recently received a major award from the United States Ministry of Defense to develop this material.
|
|
TEM (Transmission Electron Microscope) Analyses of the Effect of rBChE on β-A fibrils |
