Israel 21C, CA

A woman with backbone
By Nicky Blackburn   August 03, 2003

When actor Christopher Reeve visited Israel last week, there was one person he insisted on meeting. The person he
wanted to speak with was not a high-profile politician or fellow entertainer, but Michal Schwartz, a professor in the
Neurobiology Department of the Weizmann Institute of Science in Rehovot.

For years, Reeve, who was severely paralyzed from the neck down after a horse riding accident, has been in regular
contact with Schwartz. He has been following her work on the involvement of the immune system and inflammation in
damage to the central nervous system (CNS) with great interest.

Reeve, who set up a foundation to raise money for spinal cord regeneration research, is only one of many people around
the world who have watched with great enthusiasm as Schwartz's research has turned into a promising treatment that
could help acute spinal cord victims regain movement in their damaged limbs. Though it is still in a very early stage,
Schwartz has begun work on new research that one day might offer hope to permanently paralyzed patients like Reeves,
who suffered their spinal injuries years ago.

Though Schwartz, who holds the Maurice and Ilse Katz Chair of Neuroimmunology, is now recognized as a key player in the
field of CNS regeneration research, her journey has not always been easy. Throughout her brilliant career, she has won
many prizes, but has also managed to stir up a great deal of controversy. When she first published her groundbreaking
research on auto-immune cells, for instance, one resentful colleague told her that she should have taken the research,
hidden it in a drawer, and forgotten all about it. With typical single-mindedness, Schwartz ignored his advice and went
on to produce several more influential reports that have helped transform the way the world views the immune system.

Schwartz is not the sort of person you can ignore. Small and fiercely energetic, she tries to pack as much activity as
possible into every day, always aware that she is up against the clock. Schwartz's interest in science began at a young
age, despite the fact that she was not born into an academic family.

"I didn't have a clue what a scientist was, but I had a lot of curiosity," admits Schwartz. At the age of 10 she was
invited to take part in a trip to the Weizmann Institute because of her strong burgeoning interest in science.

"When we first approached the institute it looked to me like a place of mystery. It made me feel euphoric."

Schwartz pursued her studies at Hebrew University in Jerusalem, where she majored in chemistry, mathematics, and
physics. She gave birth to her first child, one of four, when she was 20 years old and began working towards her Ph.D.
in clinical immunology one year later in a special program. After finishing her Ph.D., she began her post doctoral work
in the US, working on the CNS, which is made up of the spinal cord, brain and optic nerve. She then returned Israel and
joined the faculty of the Weizmann Institute, where she became a tenured professor in 1985.

When Schwartz began started working in the CNS field, the only serious work being carried out was on lower vertebraes
like fish and amphibians, animals which have the ability to heal themselves when their spinal cord is damaged.
Schwartz, however, was interested in mammals, and particularly in the reasons why mammals whose spinal cords are
severed or even in some cases just partially severed, suffer complete paralysis from the point of injury down.

After studying this area for some years, Schwartz began to understand that the immune system plays a pivotal role in
the process of recovery following a CNS injury. Until then, the consensus was that immune cells that infiltrate the
brain or the spinal cord are part of the pathology, not part of the repair, and are potentially damaging to the CNS.
Schwartz discovered, however, that the immune cells, also known as macrophages, are actually part of the repair
mechanism and can be brought to the site of a lesion in the CNS, to encourage repair and renewed growth of damaged
nerve fibers.

In 1996, Schwartz founded a company called Proneuron Biotechnologies to turn her discoveries into a therapy. "I thought
this was the only way to bring these ideas into reality," recalls Schwartz. "The resources from private or public
foundations are limited and without serious funding I knew we would never be able to establish these new and
fundamental ideas."

The decision to found Proneuron has proven itself many times, says Schwartz. "Everything we did at the Weizmann was
tested again at Proneuron to make sure the findings were correct. It was the first verification that my ideas worked."

Proneuron has now developed a microphage treatment, which has been tested on eight patients suffering paralysis after
an accident. The clinical trial was completed in 2002, and showed good results on three of the patients. The most
famous of these is Melissa Holley, an 18-year-old who was paralyzed from the chest down after a road accident in
Colorado. In the wake of the treatment she has regained feeling below the injury, has the ability to move her toes and
some leg muscles, and is learning to walk with crutches and braces.

Schwartz admits that when she saw the treatment working on animals for the first time she was elated and ran with her
children to the lab to see the animals moving. With Melissa, however, she was deeply agitated and did not visit the
patient until she was about to leave Israel.

"It was the most difficult moment of my career," she admits. "I had very mixed feelings. On one hand I really wanted to
help the patient as much as possible, on the other I was worried. I never saw an adverse effect on an animal, but with
humans we couldn't control the conditions of the test. We could only give one dose and had to guess how much. There was
a lot of risk in it and I was very anxious that there might be an adverse effect. I kept asking myself if maybe the
trial was premature."

As a result of her fears, it was not until some time after she knew that Melissa was fine, that she could bring herself
to meet her.

"The meeting was extremely exciting, not just from the point of view of its success, but because I admired Melissa. She
volunteered to be our first patient, knowing that we were still exploring dosing and that there may not be any point."

Proneuron is now waiting to start a larger clinical trial on between 30-50 patients in hospitals across Europe and
America.

In the meantime, Schwartz began to explore the role of auto-immune T-cells in the CNS. She discovered that when damage
to the CNS takes place, the body sends T-cells to the site of the lesion to try to repair the problem. It was a radical
finding. Until this point, the accepted notion was that auto-immune T-cells were potentially damaging to the CNS.

"Clinicians regarded them as a disease. They were viewed as if the body was trying to attack itself and were thought to
cause auto-immune diseases such as multiple sclerosis and diabetes. We discovered, however, that the body is using
these cells for its own benefit.
We created a new concept - protective auto-immunity. In my view this was the most revolutionary concept we brought into
the field. We told the medical community: forget what you know, auto-immunity is good. It is our day-to-day mechanism
of maintaining our body. Only when there is a malfunction in it, does it cause disease."

Schwartz maintained that by boosting the level of T-cells at the site of a CNS injury by a controlled amount, they
could block the spread of injury-induced neuronal damage, and encourage better recovery after a partial injury to the
CNS. She also maintained that these T-cells could be used to treat almost any disorder of the CNS, including
Alzheimer's and Parkinson's.

"Can you imagine the power of this finding?" asks Schwartz. "Everyone is looking for a pharmacological treatment, and
we discovered a way the body can do it for itself."

Schwartz published two papers on this subject in 1998 and 1999. They were not well received by academia. "I recruited
many enemies," admits Schwartz. "When you come up with a new idea that flouts existing dogma you can expect some
resistance and skepticism. We knew that, but it's still tough to keep going when so many people object. At the
beginning I suffered a lot. I kept asking myself if I was doing the right thing. As time went by though I realized more
and more pieces were being added to the puzzle, so I had less doubt about the concept. Scientists are now repeating my
findings in different ways and using different paradigms, so we are getting approval that we were right, which is very
pleasing."

Proneuron is today using Schwartz's T-cell research to develop an innovative clinical treatment to prevent total
paralysis after partial spinal cord injury.

Schwartz has also made significant discoveries in the field of glaucoma, an optical nerve condition thought for many
years to be a disease caused by intra-ocular pressure. Schwartz suggested that glaucoma is actually a slowly
progressing neuro-degenerative disease, that can benefit from treatments designed for other neuro-degenerative
diseases.

"It took real chutzpah (daring) for us to suggest this because our knowledge of glaucoma was almost zero," admits
Schwartz. Before long, however, the scientific community began to verify Schwartz's assertion.

On the basis of her findings, Schwartz developed a method of boosting the body's immune system without risking auto-
immune disease. She showed that Copaxone, a drug developed by Teva Pharmaceuticals that induces a beneficial autoimmune
response, can be used as a vaccine that protects the optic nerve from neuronal degeneration. Teva has signed an
agreement with Proneuron to explore the use of Copaxone for glaucoma and other neuro-degenerative diseases. Clinical
trials should begin next year.

While Schwartz admits that much of her career has been isolated because of the scepticism her theories provoked, she
also acknowledges that being a woman in a man's world makes the experience tougher, and even more so as a mother.

"Israel is not the center of the world, and definitely not the center of the scientific world. If you want to remain at
the top you have to travel a lot. This is very demanding as a mother with four kids. I get to a place last and am the
first to leave. I fly nights to save days. This might not be the healthiest lifestyle, but I have to do it. In my life
there's either science or the kids. There's nothing in between."

As a result of this, Schwartz, whose youngest child is 10, is tough with her own female students. "There are many
difficulties as a mother, but the last thing I want to hear a student say is that a babysitter didn't come, or the baby
was sick. You have to find a solution between you and your partner and not to bring these problems to work."

Despite all her past achievements, Schwartz still has many important goals for the years ahead.

"From a conceptual point of view auto-immunity is the crossroads of many diseases," says Schwartz, with clear
excitement. "The mechanism in our bodies is simpler than we thought and our discoveries about auto-immunity may lead us
to even more breakthroughs in the next few years. I'm always concerned that despite what I have already achieved in the
last 20 years, I don't have enough years to accomplish what I still want to do."

One of the first tasks she has set herself is to try to find a treatment for chronically-disabled patients like Reeve,
who Schwartz has met before and greatly admires.

"Reeve did not coming to be treated, he knows he cannot be treated, but he does hope that with momentum and effort we
will be able to develop a second generation of therapy for chronic patients. We are working hard on this in my lab. It
is still in its infancy, but lately the field has moved so far that nothing is impossible at this stage," says
Schwartz.

If Schwartz does find a treatment it will be a tremendous breakthrough with far reaching consequences. By her own
admission, however, it will probably still not be enough.

"That's what drives me forward all the time. I feel what I have done so far is important, but not enough."

SOURCE: Israel 21C, CA
http://tinyurl.com/ixox

* * *

----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:[log in to unmask]
In the body of the message put: signoff parkinsn