Hope for spinal injuries

The need for effective therapies for spinal cord injuries is huge with an estimated 250,000 cases in the United States alone.Michal Schwartz, a professor of neuroimmunology at the Weizmann Institute, has dedicated years to disproving an article of faith in …

The need for effective therapies for spinal cord injuries is huge with an estimated 250,000 cases in the United States alone.Michal Schwartz, a professor of neuroimmunology
at the Weizmann Institute, has dedicated years to disproving an article
of faith in the medical profession.

A specialist in central nervous system
trauma and spinal cord injury, she sought to prove that there is positive
communication between the nervous and immune systems at the time of a
central nervous system injury.

“I focus on the cross-talk between the immune
system and the nervous system,” she says.

If that sounds like an obscure corner of medical
research, it’s not for as many as 250,000 people in the United States
who are permanently disabled because of spinal cord injury. For these
people, there is currently no cure. And each year, there are about 11,000
new cases in the U.S. alone and 34,100 around the world. It is estimated
that the per-patient lifetime costs for medical treatment, rehabilitation
and other support range from $233,000 to as much as $1.9 million.

Additionally,
lost productivity for a spinal cord injury patient has been estimated
to average $38,000 per year. The cost to healthy and active individuals
whose lives are suddenly and radically changed can’t be measured.


Until Schwartz’s work was published in the British
science journal Nature in 1998, the accepted dogma was that when a trauma
occurred, the immune system had a negative impact on the nervous system.


Schwartz, however, proved that macrophages (white blood cells) can actually
stimulate re-growth of nerve cells. In fact, she showed that in rats,
macrophages and T-cells play just as important a role in tissue repair
at the site of the injury as they do in any other tissue. T-cells can
actually protect neurons from the spread of damage, and macrophages can
help in the repair of the injured central nervous system by inducing nerve
cells to re-grow.

“I wanted to identify the body’s own mechanism
for coping with brain and spinal cord injuries. I believe that self-therapy
is the body’s best chance for repairing itself,” Schwartz said.


But Schwartz wasn’t satisfied with simply conducting
research; she wanted to apply her work to human patients in a clinical
setting, and she realized she needed a robust financial infrastructure
to do it.

Not content to let Yeda, the commercial arm of the Weizmann
Institute, find her partners, Schwartz went out and found for herself
a seed investor with the Hudson Investment Group, based in the United
States.

With a $3.1 million investment by Hudson, Proneuron Biotechnologies
was formed in 1997 as a virtual company, based in Schwartz’s lab. A year
later, it moved to the nearby Weizmann Science Park, where it is based
today.


One of the first people hired by the startup was
Valentin Fulga, senior vice president of development. Fulga is a medical
doctor who has always been interested in biotechnology. His first position
was at Pharmos, one of the oldest Israeli biotech companies, which was
begun by pioneer Haim Aviv. Fulga then went on to direct clinical trials
at Holo-Or, a medical device company, before being approached by Proneuron.


By the time Fulga joined Proneuron, the company was seeing very good laboratory
results. Experiments with rats proved that by activating macrophages in
a test tube with damaged peripheral nerve tissue and then returning the
macrophages to the damaged CNS site, researchers could restore to the
animals the partial use of previously paralyzed legs.

“When we are
talking about spinal cord injuries, we are looking at nerves in the central
nervous system and peripheral nerves,” said Fulga. “The difference
between these two types of nerves is that nerves in the central nervous
system do not regrow by themselves, and nerves in the periphery do. The
macrophages help these central nervous system cells to grow after being
injured.”


The success with animal trials encouraged Proneuron
to apply to the U.S. Food and Drug Administration for permission to begin
a Phase I clinical trial. To fund the trial, the company conducted a second
round of financing for an additional $10 million with the help of Hudson
and some Israeli venture capital funds, including Nessuah Zannex, Infinity,
Pitango and Giza.

Phase I permission was granted by the FDA in September
1999, and the company was ready to begin the trial at Sheba Medical Center
at Tel Hashomer (outside Tel Aviv) by the beginning of 2000.
As of this fall, Proneuron had six patients in its
Phase I clinical trial, which is intended mainly to show the safety of
the therapy. The company hopes to present its final results based on a
total of nine patients to the FDA by the end of 2002 at the latest.

“We
may be able to move straight into Phase II/III clinical trials with a
relatively small number of participants,” Fulga said.

Once the therapy
is proven safe and effective, it may be tried on partial injuries of the
spinal cord or on other injuries in the central nervous system.
The company faces no competition. Its technology
is unique, not the least because Schwartz’s theory went against common
thinking.

“Nobody is trying autologous macrophage therapy,”
says Fulga. “In addition, any therapy in spinal cord injury will
be additive or synergistic.” Proneuron’s business strategy is to
build cell centers for culturing the macrophages adjacent to spinal cord
injury centers (there are 16 across the U.S.) and to set up one or two
centers per country in Europe. Proneuron already has good relationships
with some centers in the U.S., but the exact type of collaboration is
not yet finalized.
Amidst all the optimism, if anyone retains caution,
it’s Schwartz herself, who has patiently seen her work develop from a
revolutionary idea to the first tentative proof that it can in fact change
human lives.

“It is too soon to celebrate,” she said.