Cell Therapy Shows Promise As Spinal Injury Cure
September 12 1999
By Yahoo News.
By David Rosenberg
JERUSALEM (Reuters) - Spinal cord injuries are responsible
for one of the human body's most frustrating phenomena -- they
simply do not heal, leaving victims permanently paralyzed as
doctors stand by helplessly.
It was long a truism in the medical profession that the
spinal cord -- part of the central nervous system (CNS) that
runs up and down the back -- could never recover from injuries,
with or without the help of drugs.
Some 11,000 people in the United States alone injure their
spinal cords annually. In the worst cases victims lose virtually
all bodily functions from the neck down.
But scientists are starting to revise their views and an
Israeli start-up, Proneuron Biotechnologies Ltd, is acting on
them.
The three-year-old company is shunning conventional drug
treatments in favor of cell therapy in a treatment that shows
promise not only in healing spinal cord injuries but overcoming
a host of other neurological diseases.
``It's really the Holy Grail to achieve spinal cord
regeneration in mammals,'' said Harry Rappaport, head of
neurosurgery at Israel's Rabin Medical Center.
Rappaport, who sits on Proneuron's scientific advisory
board, said he knew of only one other company in the world
pursuing cell therapy as a means of treating spinal cord injury.
Proneuron's answer to overcoming the spinal cord's stubborn
refusal to heal is to circumvent the central nervous system's
''immune privilege'' mechanism.
NATURAL MECHANISMS
``We deal with natural mechanisms. We're not introducing
outside, artificial molecules but we use cells to deliver a
battery of natural molecules mimicking the mechanisms of the
human body,'' Valentin Fulga, Proneuron's director of regulatory
and clinical affairs, told Reuters in an interview.
Adrian Harel, Proneuron company manager, said immune
privilege apparently evolved as a defense against diseases that
might damage the CNS -- but it also prevents injuries from
healing.
``In the central nervous system, structure is very important
for function,'' he said. ``The connection between the nerves is
very delicate; once it's disturbed, its function is, too.''
Indeed, species with simpler neurological systems, like
fish, can recover from CNS injuries.
Proneuron's solution is to take a special type of white
blood cells called macrophages, which the body uses to repair
injuries in other organs, and put them to work in the spinal
cord via a method developed by Michal Schwartz, a scientist at
the Weizmann Institute of Science and Proneuron's chief
scientist.
``Everywhere in the body macrophages are used for repair and
healing, except in the central nervous system, where they're
very scarce and ineffective, probably due to immune privilege,''
said Fulga.
To induce neuroregeneration, Proneuron takes macrophages
from the victim's blood, processes them in a special laboratory
and then injects them into the site of the injury. If effective,
the treatment will take six to 12 months to show results.
There are two limitations to this therapy. The first is that
there is a window of two weeks from the time of injury where it
can be employed; after that the damage is irreversible, so that
patients with older injuries cannot be helped.
PARTIAL RECOVERY -- FOR NOW
The second is that Proneuron's therapy will not lead to
complete recovery. ``We're sure we won't initially be able to
grow 100 percent of the nerves,'' said Harel. ``The outcome will
be variable and depend on how much physical therapy is done and
other factors.''
To date, nerve regeneration has only been conducted on
laboratory animals. But Proneuron expects to begin phase one
clinical trials on humans before the end of the year, after the
U.S. Food and Drug Administration gives the go-ahead.
Proneuron has other, related technologies further up the
development pipeline.
A spinal injury victim often suffers only partial damage
from the initial trauma. A partial loss of feeling in the leg,
for instance, may later develop into full paralysis due to the
damaging effect of the injured CNS tissue on adjacent cells.
For this, Proneuron is in the early stages of developing
another cell therapy that makes use of T-lymphocytes -- white
blood cells that help create immune reactions -- to halt the
process of secondary cell death that often follows initial
injury to the spinal cord or elsewhere in the CNS.
``As far as we know, no one is addressing this through cell
therapy,'' said Fulga, adding that the therapy could help treat
glaucoma and even stroke.
Proneuron is also conducting early experiments with an
immunosupressive agent that could lead to treatments that halt
neurological diseases like Alzheimers, Parkinsons and multiple
sclerosis.
The key is to uncover the structure of the natural Immune
Privilege Factor (IPF) molecule and re-produce it synthetically.
That is very tricky and will take much longer to develop than
cell therapies.
``The molecule is tiny and has a tendency to degrade and
disappear. When we purify we often end up with almost nothing,''
said Harel, describing the frustrations.
To speed up development in IPF, Proneuron hopes to enlist a
major pharmaceuticals company as a partner.