LOS ANGELES, Jan. 24 /PRNewswire/ -- Proneuron Biotechnologies, Inc., a privately held biotechnology company, today announced that in separate animal studies, its activated immune cell therapies promoted regrowth of severed nerve fibers and protected nerve cells from secondary damage triggered by an initial injury. The findings support the company's novel approach to treating neurological conditions by stimulating the immune system. In the company's autologous immune cell therapy, the subject's own immune cells are removed, activated, and returned to the central nervous system (CNS) where they stimulate healing.

The results of the studies were published separately in the July 1998 and January 1999 issues of Nature Medicine. Both studies were conducted by Professor Michal Schwartz, holder of the Maurice and Ilse Katz Chair of Neuroimmunology at the Weizmann Institute and Chief Scientist of Proneuron Biotechnologies, Inc. Dr. Schwartz presented the results at the Annual Meeting of the American Association for the Advancement of Science under the title "Axonal Regrowth and Protection Benefit from Inflammation and Autoimmunity: Clinical Implications."

"Proneuron scientific collaborators are uncovering much about the relationship between the immune system and the CNS," said Dr. Schwartz. "Most immune cells, including macrophages and T-cells, are excluded from the CNS due to a physiological property called 'immune privilege.' Immune privilege inhibits macrophage and T-cell activity because it can endanger neurons. However, our results suggest that when appropriately activated, the patient's own immune cells can become a therapy for many neurological conditions."

"The company is privileged to develop these autologous cell therapies representing over 15 years of work at the Weizmann Institute," said Dale S. Miller, acting president and member of the board of directors of Proneuron Biotechnologies, Inc. "These technologies may ultimately provide therapeutic benefit to many patient populations, including patients with spinal cord injury, glaucoma, peripheral nerve injury, and anterior ischemic optic neuropathy (AION -- a chronic loss of vision associated with diabetes)."

Nerve Regrowth in Spinal Cord Injury Study
In the first study, Proneuron's implanted macrophage technology restored movement in rats with severed spinal cords. Macrophages were stimulated outside the body by exposure to segments of regenerating peripheral nerves and then implanted in the severed spinal cords of 22 rats. Three control groups of rats did not receive treatment. Motor function in the rats' hind limbs was assessed for 16-19 weeks. Beginning two weeks after injury, 70% of treated animals (15 of 22) showed significant recovery of motor and behavioral activity, including vigorous voluntary movement in the hind limbs equivalent to approximately 40% of normal voluntary movement. No control animals showed any recovery.

"Although human clinical trials are obviously needed, we are very encouraged by these results," commented Dr. Schwartz. "In this study, the improved motor activity was strongly linked to regrowth of severed nerves. I believe that implanted macrophages have the ability to induce and accelerate powerful healing processes inside the CNS. This research offers new hope to victims of spinal cord injury."

Spinal Cord Injury (SCI)
Spinal cord injury (SCI) is a devastating trauma to the CNS which claims 12,000 new victims in the U.S. each year. The company estimates that approximately 250,000 people in the U.S. are permanently disabled and paralyzed due to SCI. The condition disproportionately affects young, active members of society injured in motor vehicle collisions, sports or work-related accidents. The total cost of care for SCI patients in the US is estimated to exceed $8 billion annually. No long-term treatment is available to regenerate damaged spinal cord nerves.

Protection From Secondary Neuronal Injury
In the second study, rats with severe optic nerve damage were injected with T-cells sensitized to respond to antigens of myelin basic protein (MBP), a substance present at sites of nerve damage in the CNS. Treated rats retained approximately 300% more functional neurons than did untreated animals, suggesting a powerful neuroprotective effect. In addition, electrophysiological activity in injured optic nerves was significantly reduced by injection of MBP-activated T-cells. Abnormally intense electrophysiological activity is known to play a role in progressive neuronal damage.

"This study suggests that selectively activated autoimmune T-cells can produce significant neuroprotective benefit," stated Dr. Schwartz. "The study supports the hypothesis that activated T-cells may halt secondary nerve damage by putting injured neurons in a state of rest. Quiet neurons may be less likely to over-stimulate their neighbors."

Secondary Neuronal Damage and Neurological Impairment
Nerve cells in the central nervous system (CNS), known as neurons, are harmed by injury to the brain or spinal cord. Most neuronal injury and death, however, does not typically occur at the time of initial injury. Many more neurons suffer progressive injury and die in the hours, days or weeks following CNS trauma. Neurons harmed in the initial injury are believed to become overexcited and over-stimulate neighboring cells, resulting in a cascade of secondary neuronal injury and death. Secondary neuronal damage frequently leads to serious neurological impairment following CNS injury, including loss of coordination, difficulty walking, or paralysis; memory loss, inability to concentrate and other cognitive deficits; and loss of vision or blindness.

Background: Immune Privilege
Compared to other body tissues, CNS tissues have a limited ability to recover from injury or insult. Recent research indicates that this is related to the active suppression of the immune system in the CNS, a physiological property known as "immune privilege." The CNS, for example, contains neither T-cells nor macrophages, the two most powerful immune system cells in the body. T-cells attack foreign antigens in the body while macrophages engulf, absorb and remove damaged cells and debris. Instead, the CNS is shielded from foreign organisms and substances by a tight screen known as the "blood-brain barrier."

Immune privilege is believed to protect neurons from certain diseases and auto-immune disorders. Macrophages and T-cells, for example, may secrete substances toxic to neurons. However, immune privilege also limits the ability of CNS nerve cells to protect themselves from disease and injury. Proneuron believes that its activated T-cell therapy has the potential to selectively neutralize immune privilege and boost the body's natural defense mechanisms.

Proneuron Company Profile
Proneuron Biotechnologies, Inc. is a biotechnology company developing novel therapies for acute and chronic neurodegenerative diseases, including spinal cord injury and optic neuropathy. The company's strategy is to achieve, proof of concept for its therapeutics in human clinical trials; seek late-stage development and marketing partners; and ultimately to establish four CNS therapy centers where patients can receive activated macrophage and T-cell therapies.

The company has three proprietary technology platforms for neuroprotective and neuro-regenerative therapies: autologous macrophage therapies to regenerate CNS nerve fibers; autologous T-cell therapies to protect nerve cells from neurodegenerative injury; and immune Privilege factor (IPF) therapy to stimulate the CNS immune response. In preclinical studies conducted by the company, its therapies have promoted regrowth of severed spinal cord fibers and optic nerve fibers, and protected neurons in multiple animal models

By mid-1999, the company expects to initiate Phase I/II human clinical trials of its autologous macrophage therapy to treat spinal cord injury (SCI). Such trials will be conducted in Israel under an Investigational New Drug (IND) application filed with the United States Food & Drug Administration (FDA). Proneuron is in the process of establishing a current Good Manufacturing Practice (cGMP) facility in Israel to support these clinical trials.

Proneuron was founded in 1996 to commercialize technologies being developed at the Weizmann Institute of Science in Rehovot, Israel. Proneuron has obtained an exclusive worldwide license to uses of such technologies from Yeda Research and Development Corporation, Ltd., the commercialization arm of the Weizmann Institute. Since inception, the company has raised equity financing from Israeli and U.S. investors, including AG Tech, DS Polaris II, Chase Equity Associates, Hudson Investment Group and Omega.

Press releases and corporate information from Proneuron Biotechnologies, Inc. are available on the Internet at www.Proneuron.com.