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Israeli student develops novel drug that mimics feeling of ‘fullness’

Posted By ISRAEL21c Staff On June 7, 2007 @ 9:57 am In | No Comments

A Hebrew University of Jerusalem doctoral student who has developed an innovative drug that gives people the feeling of satiety is one of three to win a Kaye Innovation Award, which will be presented at the Hebrew University’s 70th Board of Governors meeting this week.

The prizes have been awarded annually since 1994, when they were established by English pharmaceutical industrialist Isaac Kaye to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential that will benefit the university and society.

Yaniv Linde, a 32-year-old student of Prof. Chaim Gilon in the department of organic chemistry, mimicked the activity of the naturally occurring hormone called aMSH. This hormone is naturally excreted during eating and binds to a receptor in the brain called MC4R.

When this “communication” occurs on a substantial level, the brain sends out a signal that one feels “full.” Linde and colleagues synthesized a peptide (a compound linking two or more amino acids) that can serve as an analog to the naturally occurring aMSH hormone. They were able to demonstrate that their peptide, which they call BL-3020, displayed good metabolic stability to intestinal enzymes when swallowed, and that it was able to cross the intestinal wall and gain access into the bloodstream. Once in the blood, it could make its way to the MC4R receptor and “close the circuit” to send out the “full” signal.

The result is that a person seriously wishing to overcome obesity could take this compound orally in order to curb his appetite and lose weight naturally. In experiments with mice, it was shown that a single oral administration of BL-3020 led to reduced consumption over a period of 24 hours. Over a 12-day period of daily dosages, the mice weighed 40 percent less than the average for mice of their size and age that did not get the compound.

The peptide has been patented in Europe and the US, and a commercial firm, BioLineRx Ltd. of Jerusalem, has purchased development rights from Yissum, Hebrew University’s technology transfer company, and is currently working towards creating a commercial anti-obesity drug.

Meanwhile, Prof. Leo Joskowicz of the Hebrew University School of Engineering and Computer Science has received a Kaye Award for developing a miniature robot for precise positioning and targeting in keyhole neurosurgery.

While recent advances in neurosurgery have made it possible to precisely target areas in the brain with minimum invasiveness using a small hole to insert a probe, needle or catheter, there remains a disadvantage: The small size of the openings reduces or eliminates direct site visibility and requires greater dexterity, stability and precision by the surgeon.

The new device has made it possible to guide surgical procedures with great accuracy. Joskowicz, the founder and head of the university’s Computer-Aided Surgery and Medical Image Processing Laboratory, overcame the problems that could lead to misplacement of the surgical instrument and resulting hemorrhage and severe neurological complications. The image-guided system, the university said, offered precise, automatic targeting of structures inside the brain, with the miniature robot programmed with detailed information obtained from preoperative scans of the patient.

During surgery, the robot is directly affixed to a head clamp or to the patient’s skull. It automatically positions itself and locks itself in place to serve as a guide for insertion by the surgeon of a needle, probe or catheter to carry out the procedure. This reduces pain and is compact and easy to use in a wide variety of neurosurgical procedures.

The two-year project was funded by a grant from the Ministry of Trade and Industry through Yissum, which has commercialized it for product development by Mazor Surgical Technologies.

The third Kaye winner is Erez Podoly, a joint student of science dean Prof. Hermona Soreq and head of the Wolfson Center for Applied Structural Biology Prof. Oded Livnah.

Although numerous drugs have been developed over the years to alleviate the symptoms of Alzheimer’s disease, there is still no real cure to halt it. Podoly, a graduate student in biological chemistry, has developed an approach that holds out promise of providing natural brain protection against the spread of this disease.

Podoly, a 34-year-old immigrant from New York, and his colleagues set out to design a blocker for the neurotoxic effects of a peptide involved in Alzheimer’s, using the Butyrylcholinesterase (BChE) protein, which was cloned and engineered in their lab. The concentration of BChE in the brain increases with age, a fact overlooked so far, but which for Podoly and his colleagues seemed highly relevant to the progress of Alzheimer’s. Using BChE purified from human blood and short synthetic peptides, they were able to reduce the formation of fibrils in the brain involved in the disease.

US company PharmAthene Inc. produced engineered human BChE that was introduced into the milk of transgenic goats. Podoly’s team showed that the goat-derived BChE efficiently interacts with and reduces amyloid fibrils formation. They anticipate that recombinant human BChE produced in the milk of transgenic goats and/or synthetic peptides derived from BChE can become novel prophylactic or therapeutic agents for slowing the progression of senile plaque formations in the brains of Alzheimer’s patients. Further research, leading to clinical tests on humans, is planned.

(Originally appeared in The Jerusalem Post)

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