CARMIEL, Israel, /PRNewswire-FirstCall/ — Protalix BioTherapeutics, Inc. (Amex: PLX), noted today that prGCD, the Company’s proprietary recombinant form of Glucocerebrosidase (GCD), which is used as an enzyme replacement therapy for Gaucher disease, was named one of the Five Most Promising Drugs Entering Phase III Trials in the third quarter issue of The Ones to Watch report published by Thomson Scientific. Thomson Scientific, a part of The Thomson Corporation, is a leading provider of information solutions to the worldwide research and business communities. Thomson Scientific states that the third quarter issue of The Ones to Watch report provides expert insight into the five most promising drugs entering each new phase of clinical development between July and September 2007.

Dr. David Aviezer, the Company’s Chief Executive Officer and President, said, “We have been pleased with the progress that we have seen thus far in our clinical development program of prGCD as a treatment of Gaucher disease. During the third quarter of 2007, we reached an agreement with the United States Food and Drug Administration on the final design of our pivotal phase III clinical trial of prGCD, through the FDA’s special protocol assessment (SPA) process and began enrolling patients in the trial. We have been treating patients since August 2007, and are initiating study centers worldwide. We believe that the results from the phase III clinical trial will be positive, and will lead to the commercialization of prGCD as a treatment for Gaucher disease patients.

About Protalix BioTherapeutics, Inc.

Protalix is a biopharmaceutical company. Its goal is to become a fully integrated biopharmaceutical company focused on the development and commercialization of proprietary recombinant therapeutic proteins to be expressed through its proprietary plant cell based expression system. Protalix’s ProCellEx(TM) presents a proprietary method for the expression of recombinant proteins that Protalix believes is safe and scalable and will allow for the cost-effective, industrial-scale production of recombinant therapeutic proteins. Protalix is enrolling and treating patients in its pivotal phase III clinical trial in Israel, the United States and other locations for its lead product candidate, prGCD, for its enzyme replacement therapy for Gaucher disease, a lysosomal storage disorder in humans, and has reached an agreement with the United States Food and Drug Administration on the final design of the pivotal phase III clinical trial through the FDA’s Special Protocol Assessment (SPA) process. Protalix is also advancing additional recombinant biopharmaceutical drug development programs.

Safe Harbor Statement:

To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to attract and retain partners for our technologies and products under development, the identification of lead compounds, the successful preclinical development of our products, the completion of clinical trials, the review process of the FDA, foreign regulatory bodies and other governmental regulation, and other factors described in our filings with the Securities and Exchange Commission. The statements are valid only as of the date hereof and we disclaim any obligation to update this information.

For additional information, contact Protalix BioTherapeutics at:
investors@protalix.com
AMEX IR Alliance for Protalix BioTherapeutics
Lee Roth / David Burke
212-896-1209 / 1258
lroth@kcsa.com / dburke@kcsa.com

SOURCE Protalix BioTherapeutics, Inc.

ProCellEx™ Overview:

ProCellEx™ is the proprietary production system developed by Protalix, based on their plant cell culture technology for the development, expression and manufacture of recombinant proteins. This expression system consists of a comprehensive set of capabilities and proprietary technologies, including advanced genetic engineering and plant cell culture technology, which enables the production of complex, proprietary and biologically equivalent proteins for a variety of human diseases. This protein expression system facilitates the creation and selection of high expressing, genetically stable cell lines capable of expressing recombinant proteins. The entire protein expression process, from initial nucleotide cloning to large-scale production of the protein product, occurs under cGMP-compliant, controlled processes. The Protalix plant cell culture technology uses plant cells, such as carrot and tobacco cells, which undergo advanced genetic engineering and are grown on an industrial scale in a flexible bioreactor system. Cell growth, from scale up through large-scale production, takes place in flexible, sterile, polyethylene bioreactors which are confined to a clean-room environment. Protalix bioreactors are well-suited for plant cell growth using a simple, inexpensive, chemically-defined growth medium as a catalyst for growth. The reactors are custom-designed and optimized for plant cell cultures, easy to use, entail low initial capital investment, are rapidly scalable at a low cost and require less hands-on maintenance between cycles. This protein expression system does not involve mammalian or animal components or transgenic field-grown, whole plants at any point in the production process.

The unique ProCellEx™ system is capable of producing proteins with an amino acid structure practically equivalent to that of the desired human protein, and with a very similar, although not identical, glycan, or sugar, structure. Our internal research and external laboratory studies have demonstrated that ProCellEx™ is capable of producing recombinant proteins that exhibit a glycan and amino acid structure similar to their naturally-produced human counterparts. In addition, proteins produced by this ProCellEx™ system maintain the biological activity that characterizes the biological activity of naturally-produced proteins. In collaboration with Israel’s Weizmann Institute of Science, Protalix has demonstrated that the three-dimensional structure of a protein expressed in their proprietary plant cell-based expression system retains the same three-dimensional structure as exhibited by the mammalian cell-based expressed version of the same protein (Shaaltiel et al, Plant Biotechnology J. 2007). Based on these results, the people at Protalix believe that proteins developed using their ProCellEx™ protein expression system have the intended composition and correct biological activity of their human equivalent proteins.

4A331781-E8A5-4DA2-A52B-47E9B0EA209F.jpg
A surface preparation of arterial endothelium. The endothelial nuclei appear blue; the cell boundaries are stained black with silver nitrate. Credit: School of Anatomy and Human Biology, University of Western Australia

Interventional Cardiologists Reduce Risk Of Stents By Magnetizing Endothelial Cells

ScienceDaily.com — Interventional cardiologists used magnetic particles to accelerate the process of healing after the placement of a stent. To do this, they extract cells from the interior of a patient’s blood vessels, cultivate them, and insert iron-based paramagnetic particles into the cells. When the cells are reintroduced to the blood, this attracts them to the magnetic coating on the stent, creating a film of living cells that promotes tissue healing and ultimately reduces the risk of blood clot formation.

A common heart problem may now have a magnetic solution. Researchers are using the laws of attraction to make heart stents that unclog blood vessels more safely.

A puppy named Cash is the newest member of Bob Stortron’s family. At 68, Stortron says it’s not too hard keeping up with him. A few years ago, it may have been more difficult. Stortron’s heart was fading, and he had to have a stent put in. Stents reinforce blood vessel walls to keep vessels open and blood flowing.

“When you’re talking about numbers of patients in the millions, 1 percent can add up to pretty large numbers,” Gurpreet Sandhu, M.D., Ph.D., a cardiologist at Mayo Clinic in Rochester, Minn., said of those who need heart stents.

Normally, it takes weeks for endothelial cells to coat stents and blood vessels to heal. Now, interventional cardiologists are testing magnetic stents that attract those cells faster. First, cells are taken from the blood and tagged with iron microspheres. Then, a magnetic stent is threaded through the blood vessel. At last, tagged cells are sent through the blood vessels to see if they are attracted to the stent.

“This will hopefully mean fewer repeat procedures on patients and better quality of life for our patients,” Dr. Sandhu said.

Dr. Sandhu says the technology speeds up healing to just days, requires fewer blood thinners and lowers the risk of blood clots.

Stortron says he couldn’t ask for a better life, and he’s content spending the rest of it enjoying his family.

“I hope I’m around for a long time, but I don’t have control over that button,” Stortron said.

WHAT MAKES MATERIALS MAGNETIC? Magnetism comes from the constant movement of charged electrons in atoms. As electrons swirl around an atom, they create an electrical current, and whenever electricity moves in a current, a magnetic field is created. So magnetism is a force between electric currents: two currents flowing in the same direction attract, while those pulling in opposite directions repel. The reason some materials are magnetic, while others are not, has to do with how the electrons are ordered. A magnet is an object made of magnetic materials; naturally occurring magnets are known as lodestones. Every magnet has at least one north pole and one south pole. In fact, if you take a bar magnet and break it into two pieces, each of the smaller pieces will still have a north and south pole. The Earth itself is a giant magnet with a north and south pole, which is why a magnetic compass’s needle always points north/south.

WHAT ARE STENTS? A stent is essentially a small piece of metal “scaffolding” that pushes arterial plaque to the side and provides a framework to keep the blood vessel open so that the blood can flow freely through it. Stents have been used for many years to clear blockages in the arteries of the heart and neck.

The American Physical Society and the Materials Research Society contributed to the information contained in the TV portion of this report.

endothelial cell

8B9175F9-B444-4F5A-A25B-4CEB708D99E3.jpg
endothelial cells stained with hydroethidine

Endothelial cells are squamous (flattened) cells, large numbers of which make up the lining of blood vessels and lymphatic vessels. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. A layer of epithelial cells is called an endothelium.

An individial endothelial cell has a central nucleus, is very flat (only about 1-2 μm thick), and measures some 10-20 μm in diameter. The intercellular junctions between endothelial cells overlap, thus helping to make a tight seal, for example in the wall of a blood vessel.

Endothelial cells play a key role in many phenomena to do with blood and blood vessels, including:

· Formation of new blood vessels (angiogenesis)

· Vasoconstriction and vasodilation, and hence the control of blood pressure

· Blood clotting (thrombosis and fibrinolysis)

· Atherosclerosis

· Inflammation and swelling (oedema)

Endothelial cells also control the movement of substances, and the passage of white blood cells (leukocytes), into and out of the bloodstream.

Some organs have highly differentiated endothelial cells for carrying out specialized filtering functions. Examples of such unique endothelial structures include the glomerulus of the kidney and the blood-brain barrier.

4151D347-6FE6-432E-9DF9-1364BD1CFDBA.jpg
Diagram showing the location of endothelial cells

4E887EC6-2AFF-4C85-B317-02DD5B2226B7.jpg

PHILADELPHIA — When cardiologists prop open blocked arteries with the lifesaving metal cylinders known as stents, inevitably there is some damage to the cells that line the blood vessel walls _ damage that may not heal properly on its own.

A team of Philadelphia researchers now thinks it can address the problem by borrowing a trusty concept from Physics 101: magnets.

The scientists implanted stents in the carotid arteries of rats, then placed the animals between two large electromagnets, temporarily magnetizing the stents. The rats were then injected with healthy repair cells that had been loaded with tiny magnetic particles, which were simply drawn through the bloodstream to the right location.

The procedure, reported this month online and in the print issue of Proceedings of the National Academy of Sciences, is just one way researchers are exploring the use of magnets as medical tour guides through the byways of the human body.

The authors of the paper, from Children’s Hospital of Philadelphia and Drexel and Duke Universities, also envision using magnets to deliver drugs and even designer genes _ and not just to the insides of arteries. Stents used in the bile duct, urinary tract, esophagus and lungs also could be targeted _ as could other kinds of metal implants that are used in orthopedic procedures.

Biomedical engineer Robert S. Langer, a Massachusetts Institute of Technology professor who was not involved with the paper, praised the new research for its “cleverness.”

“It seems to me that could be universally applicable,” Langer said.

In blood vessels, the goal of the magnet-based therapy is to help prevent stented arteries from becoming reobstructed, whether by blood clots or abnormal cell growth. Further study is needed, and the procedure is a few years from being tried in humans.

There’s a big market for it. Bare-metal stents were approved for use in 1994, followed by the advent of the drug-coated variety in 2003. They’ve become so popular for use in heart patients _ more than 600,000 were implanted in 2004 nationwide _ that coronary bypass operations have declined as a result.

But both kinds of stents can have unwanted consequences, such as damage to the clot-resistant endothelial cells that line arteries, said cardiologist Robert J. Levy, senior author of the new paper.

When bare-metal stents are implanted, sometimes abnormal smooth-muscle cells will grow before the endothelial cells can heal, reobstructing the artery. Drug-coated stents help prevent this abnormal growth, but they also inhibit the regrowth of healthy endothelial cells, so blood clots are a concern.

Solution: Deliver healthy endothelial cells to the proper location.

That’s where the magnets come in, said Levy, who directs the cardiology research laboratories at Children’s Hospital.

First, the team loaded the endothelial cells with magnetic nanoparticles _ tiny spheres of a biodegradable polymer that had been impregnated with iron oxide. These cells were then injected into five stented rats that sat between the magnets.

The cells had been engineered to have a luminescent “reporter gene,” so once they stuck to the stents, they could readily be seen with the proper imaging equipment, Levy said. Sure enough, the glowing particles were visible in the very diamond-shaped pattern of the mesh stents to which they adhered.

Drexel’s Boris Polyak, the co-lead author of the paper, said further study was needed to see if such cells would grow permanently into the surrounding tissue.

“We expect them to adhere, to proliferate, and to grow,” Polyak said.

When the stents were examined soon after the injections, the cells already had begun to attach to the artery wall, Levy said. (The researchers used cells from a cow because they were readily available, but they plan to follow up with a rat’s own endothelial cells.)

The polymer used to make the particles is of the same kind already used for biodegradable sutures, and it is easily broken down by the body. The iron oxide was at low enough levels that it was cleared by the rats’ cells with no ill effects.

But Levy said in the future, his team hopes to make nanoparticles with even lower levels of iron oxide.

That would be possible if physicians made use of the much stronger magnetic field in a device that is already widely found in hospitals: the MRI machine.

The magnetic field in an MRI is about 10 times stronger than what was used with the rats; as a result, physicians could use magnetic particles with much less iron oxide, he said.

MIT’s Langer said he wasn’t sure that an MRI machine could be used for this purpose without modification. So testing the machines is among the next projects in Levy’s lab.

RedOrbit.com/science, February 27, 2009 — U.S. medical researchers have discovered a grid of small arteries at the surface of the brain redirects and controls blood flow following a stroke.

University of California-San Diego scientists say they found the mesh-like network adjusts to restore normal supply when blood slows after a stroke.

This is optimistic news, said Professor David Kleinfeld, whose team studies blood flow in animal models of stroke.

Damage from stroke can continue for hours or even days as compromised brain tissue surrounding the core injury succumbs to deprivation of oxygen and nutrients, the researchers said.

This is the area doctors are trying to protect after a stroke, said Andy Shih, a postdoctoral fellow in Kleinfeld’s group who conducted the experiments. Those neurons are teetering on the edge of death and survival.

The researchers said previous work found blood flow can persistently slow after a stroke, which would hinder the delivery of drugs that might help recovery. But, they said, those studies only measured the speed of the blood. By measuring both the speed of blood cells moving through individual small arteries and the diameters of the same vessels, the scientists found the arteries dilate to maintain a constant delivery of blood cells.

The research that included Patrick Drew, Philbert Tsai, Beth Friedman and Dr. Patrick Lyden appeared in the Jan. 28 online edition of the Journal of Cerebral Blood Flow and Metabolism.