ISRAELI RESEARCHER LOWERS BLOOD PRESSURE WITH CANNABIS COMPONENT

A new method for lowering blood pressure with a compound that
synthesizes a cannabis (hashish or marijuana) plant component has been
developed by a Hebrew University doctoral student in
pharmacology.

For his work on the cardiovascular activity of cannabinoids (chemical
compounds derived from cannabis), Yehoshua Maor has been named one of
the winners of this year's Kaye Innovation Awards, to be presented on
Tuesday during the university's 69th annual board of governors meetings.

The Kaye Innovation Awards, established by British pharmaceutical
industrialist Isaac Kaye, have been given annually since 1994 to
encourage HU faculty, staff and students to develop innovative methods
and inventions with good commercial potential to benefit the
university and society.

Not all patients respond well to conventional hypertension
drugs.

But the cannabis plant, through its chemical compounds, has been shown
to have a beneficial, hypotensive effect.

But a drawback in the therapeutic use of cannabinoids has been the
undesirable psychotropic properties such as hallucinatory effects.

Attempts to separate the hypotensive action from their psychotropic
properties have been only partially successful until now.

Working under the supervision of Prof. Raphael Mechoulam at the HU
School of Pharmacy, Maor - a native of Brazil who immigrated to Israel
in 1998 - has created a synthetic version of a minor cannabis
constituent named cannabigerol, which is devoid of psychotropic
activity. In laboratory experiments with rats, in collaboration with
Prof. Michal Horowitz, it was found that this novel compound reduced
blood pressure when administered in relatively low doses.

Additional testing also showed that the compound also brought about
another beneficial effect - relaxation of the blood vessels.

A further beneficial property observed in work carried out with Prof.
Ruth Gallily was that the compounds produced an anti-inflammatory response.

Maor says these qualities could be combined to create a valuable new
clinical drug with major market potential, especially for diabetic
patients suffering from hypertension, since reductions in blood
pressure can decrease the risk of diabetes complications and in others
with metabolic irregularities.

Meanwhile, former Russian immigrant Elena Khazanov, 34, will also
receive a Kaye Prize for developing a novel method for combining two
anti-cancer drugs into a single delivery system, thereby dramatically
improving treatment efficacy.

Khazanov, who arrived here 12 years ago, developed her drug delivery
system as a PhD student under the tutelage of Prof. Yechezkel
Barenholz of the Hebrew University-Hadassah Medical School's
biochemistry department.

Khazanov used an approach called combination therapy, in which two or
more agents are introduced within a single delivery unit, with the
result that the combination has a better beneficial chemotherapeutic
effect than otherwise would be possible.

Her work was based on the previous success of HU scientists with the
delivery system for an anti-cancer drug, doxorubicin (DXR), which
resulted in development of DXR delivery through sterically stabilized
liposomes (SSL), which are ball-like fatty molecules.

A highly successful medication based on that research has been
manufactured by SEQUUS Pharmaceuticals and is marketed as Doxil.
Khazanov aimed to combine DXR with ceramides, a family of fatty
molecules found in high concentrations within cell membranes.

These act as signaling molecules, triggering programmed cell death in
many types of cancer cells.

However, the physical and chemical properties of ceramides make them
unusable by themselves for therapeutic application in vivo. Her
efforts ultimately proved successful in formulating a novel drug
delivery system consisting of SSL that contained both DXR and ceramides.

In laboratory tests on mice, the synergism between the two drugs
resulted in an improved therapeutic benefit over Doxil alone.

The fact that both were delivered by one tiny SSL liposome enables
long plasma circulation time and liposome-selective delivery to the
tumor site by their introduction into the tumor through pores present
in the tumor blood vessels.

Additional trials, including therapeutic efficacy studies in mice
bearing different tumors, plus toxicology studies of this new liposome
formulation, are continuing to ultimately enable human clinical
trials. Patents have been secured through Yissum, HU's technology
transfer company, to enable further development of the delivery
system. New, non-invasive therapies for treating diseases such as
basal cell carcinoma, viral and microbial deep skin infections and
erectile dysfunction are being developed by Prof. Elka Touitou,
another Kaye Prize recipient from the pharmacy school.

The new approach uses a specially designed, patented topical delivery
system known as Ethosome for targeting drugs directly to the disease
site. Touitou invented the system with a group of her students and
postdoctoral fellows.

Ethosome provides a dermal delivery system that overcomes the natural
skin barrier that has prevented anti-cancer drugs applied on the skin
from reaching their targets.

Drugs encased in Ethosome are able to penetrate even into the deep
skin layers where basal carcinoma cells occur, thereby providing a
non-invasive alternative to surgical intervention. A number of
clinical studies, including a recent one on the use of
Ethosomalprostaglandin for treatment of impotence, have shown their
efficiency, and the delivery system can be used in cosmetic compounds.

New and safer compounds for treatment of epilepsy patients and those
suffering from other neural disorders have been developed by Prof.
Meir Bialer and Prof. Boris Yagen. Their work at the pharmaceutics,
medicinal chemistry and natural products department at the pharmacy
school is also being recognized by a Kaye Prize they will share.

They developed a potential alternative for valproic acid (VPA), one of
the leading anti-epileptic drugs, which has been used as a central
nervous system treatment since 1967, but which also has serious safety
drawbacks. Its side effects can cause damage especially to children or
women of child-bearing age. Patents have been obtained by Yissum.

The Barenholz Prize for Creativity and Originality in Applied Research
will be presented to a 29-year-old HU doctoral student at the pharmacy
school, for her work in discovering a way to prevent restenosis -
recurrent blocking of coronary arteries after angioplasty (balloon
therapy).

The award, named for its donor, cancer researcher Prof. Yehezkel
Barenholz, will be presented during the board meetings to Hila
Epstein-Barash. In her research, she and her colleagues hypothesized
that if the macrophages that accumulate in the area of the
angioplastic treatment could be inactivated, the problem could be solved.

The problem was how to deliver a cell-specific drug that could achieve
this. In their research they found that this could be accomplished
through the use of bisphosphonates - bone-seeking agents used
clinically to treat osteoporosis - which have high affinity to calcium
and are assimilated into bone tissue by osteoclasts - which are
closely related to macrophages. The problem before them was how to
reach the targeted area of macrophages in the blood vessels, since the
drug alone, due to its chemical makeup, is not able to cross cell membranes.

The researchers subsequently found that by encapsulating the
bisphosphonates in liposomes, the drug could be delivered to the
macrophages in the blood vessels that had been opened by angioplasty.
The scientists found that a single injection of liposomes containing
bisphosphonates, soon after angioplasty, significantly prevented
restenosis in rat and rabbit models, markedly reducing the thickness
of the inner wall of the affected arteries and leaving enough room for
the blood to circulate. Pre-clinical trials are now proceeding in
Australia, using this procedure which is non-toxic and presents no
side effects.