MED/NEURO: Human trials of spinal nerve regeneration in ~1 year?
Sun, 12 Sep 1999 13:38:01 EDT

Anyone know more details about this outfit? A stock play?

Sunday September 12 1:42 AM ET
Cell Therapy Shows Promise As Spinal Injury Cure 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.


``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.


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.