Background information: Visit to Israel of Christopher Reeve
July 28-31, 2003

The Sheba Medical Center at Tel Hashomer, Israel

The history of the Sheba Medical Center at Tel Hashomer, parallels that of the State of Israel. It was originally built by the US Military in 1941-2, subsequently became a British army hospital, and in 1948 became an Israeli army hospital. From there it has grown into the largest and most comprehensive medical facility in the Middle East.

The Center’s 150-acre site has 1,900 beds, and serves 125,000 inpatients and 700,000 outpatients annually. Approximately 5,800 healthcare workers and support staff support the faculty of more than 800 physicians.

The Medical Center serves all of Israel’s multi-ethnic population; Jews, Muslims, Druses and Christians; civilians, soldiers and visitors, while providing facilities and treatment to patients from several neighboring countries. The Center is one of the most prominent teaching and research hospitals in the region, in partnership with the Sackler School of Medicine at Tel Aviv University and the prestigious Weizmann Institute for Science for which it serves as the clinical venue.

Sheba has one of the largest trauma centers in Israel and houses facilities for victims of major nuclear, biological and chemical terror attacks. It is the home of Israel’s public policy think tank, the National Institute of Epidemiology and Health Policy Research – under the direction of Sheba’s Director General, Professor Mordechai Shani -, which is charged with providing strategies for meeting Israel’s national health care objectives. The Center is also home to the Israel Center for Medical Simulation which – among other initiatives – has built a ‘virtual hospital’, under the direction of Dr. Amitai Ziv, to train doctors, nurses and paramedics through sophisticated simulation of trauma and diagnostic protocols.

Sheba Medical Center has many national responsibilities and, amongst others, is the site of the National Center for Spinal Cord Injuries, located at the Rehabilitation Center, which is part of Sheba’s Rehabilitation Hospital, under the direction of Professor Shlomo Noy.

Sheba’s Rehabilitation Center

The Center has for years been recognized as an international leader in providing long-term physical and emotional rehabilitation through a multi-disciplinary professional staff. The Rehabilitation Center works to restore our patients’ ability to function as normally and as comfortably as possible, work that takes effort every moment of every day. Rehabilitation is the human side of medicine, often less glamorous and not associated with spectacular cures. Rehabilitation at Sheba is about helping patients effectively cope with deep pain and frustration. It’s about helping them ‘choose life.’

The Rehabilitation Hospital includes Orthopedic and Neurological departments, a Day Hospitalization Clinic, two swimming pools for Hydro Therapy, a Center for Multiple Sclerosis and a Department for Respiratory Rehabilitation, under the direction of Dr. Arie Wollner, where chronically ventilated patients are weaned off their respirator – 60 percent fully and an additional 30 percent part-time. All the physicians and nurses in this department are specialized in Intensive Care, too.

The Neurological Rehabilitation Department, under the direction of Dr. Gabriel Zeilig, serves as the National Center for Spinal Cord Injuries. This is the only department in Israel that specializes in treating the wide variety of life challenges facing paraplegic or quadriplegic patients.

The ‘Steps’ Clinic for Mobility Rehabilitation treats handicapped patients who need special walking methods tailored to their individual needs, aimed at improving their mobility. Besides strengthening their arm and leg muscles on fitness bikes, patients with spinal cord injuries undergo stand-up exercises in a special device, train the use of RGO walking braces, and exercise correct walking motions on a sophisticated treadmill, strapped in a harness that carries their body weight and under the guidance of a therapist.

The Israel Center for Medical Simulation

The Israel Center for Medical Simulation, under the direction of Dr. Amitai Ziv, was established during the years 2000-2001 at Sheba Medical Center, Tel Hashomer. The Center’s purpose is to lead a nationwide effort to introduce new standards and innovative approaches to health care training and patient-safety education for the benefit of the people of Israel. The 800 square meter Center is designed as a virtual hospital and encompasses the whole spectrum of medical simulation modalities. These include simulated patients – role-playing actors for clinical skills and communication training -, advanced task trainers – for training of complex manual skills -, and cutting-edge, computer-driven, full-body mannequins, that enable simulated team training for challenging/high risk clinical conditions. State-of-the-art audiovisual equipment and one-way mirror observation booths ensure effective debriefing and constructive feedback to trainees.

The ultimate goal of health professionals is the provision of the safest and best possible quality care to patients. Highly competent, well-trained, humane health care providers are the core element to achieve this goal. Simulation based medical education has been recognized as a powerful tool in addressing patient safety and quality-care training. Our goal at the Center for Medical Simulation is to enhance patient safety and quality of care by improving clinical and communication skills of health providers.

The Israel Center for Medical Simulation established itself as a unique national and global role model and has gained national and international recognition as a vitally important addition to Israel’s medical education network. With Dr. Ziv’s recent briefings to the United States Congress and the Federal Department of Health and Human Services Emergency Preparedness Branch, US health authorities have recognized the Center as a world leader in this field. Furthermore, major US Institutions such as the Mayo Clinic, the Cleveland Clinic and the University of Chicago are already collaborating with our Center as they advance their planning of simulation centers based on our model.

How damage to the central nervous system is linked to the immune system

Research by Prof. Michal Schwartz of the Neurobiology Department at the Weizmann Institute of Science

Prof. Michal Schwartz of the Neurobiology Department at the Weizmann Institute of Science has found that when the central nervous system (CNS) becomes damaged, inflammation-causing immune cells called macrophages are recruited to the injured site at a low rate, and those that are recruited fail to become optimally activated and effective. In contrast, macrophages "summoned" to heal peripheral nerves are sufficiently activated and heal the damage effectively.

Armed with this understanding, the researchers managed to partially overcome the limited ability of the damaged CNS to recruit and activate the macrophages. They incubated macrophages in a test tube, properly activated them and then returned them to the damaged site in the CNS of the paralyzed rat. The transplanted macrophages supported partial recovery of motor of the otherwise paralyzed rats.

Another intriguing aspect of the intricate relationship between the CNS and the immune system is the role played by autoimmunity in the process of recovery from CNS injury. The researchers found that the same cells that cause autoimmune disease – a condition in which the immune system attacks the body’s own tissues – can actually be beneficial to the damaged CNS.

It was traditionally believed that autoimmune disease results from a mistake made by the immune system, a failure to distinguish the "self" from the enemy "non-self." Studies by Prof. Schwartz and her team have showed that autoimmunity is a purposeful immune mechanism, unless it malfunctions. Accordingly, this team has proposed that an autoimmune disease results from lack of control of the autoimmunity, and that autoimmunity, if well controlled is the body’s mechanism of defense against self-enemies that are emerging within.

Schwartz and her colleagues showed that immune cells called T lymphocytes that target the body’s components (and are therefore by all criteria autoimmune cells), are the very same cells that limit consequences of nerve damage caused to the spinal cord or any part of the brain or visual system. When injected into rats with damaged brain, spinal cord, or optic nerve, these T cells reduced paralysis and promoted post-traumatic recovery from spinal cord injury or brain trauma or any chronic neurodegenerative disease.

This finding may explain why autoimmune T cells are so common and present even in the immune systems of healthy people: their original function may have been to maintain the integrity of the central nervous system. Only when this function for some reason goes awry, does autoimmune disease occur. "By selectively augmenting the activity of autoimmune T cells, we found that it is possible to protect injured nerves without the threat of causing autoimmune disease," says Prof. Schwartz.

Thus, it was discovered that immune cells can function as the body’s mechanism of repair. They are needed for well-synchronized and orchestrated local repair of the damaged spinal cord or brain. An insufficient or non-optimal recruitment of these cells apparently contributes to the devastating outcome following injury. These understandings created the basis for the current repair strategies devised by Prof. Schwartz and her team.

Immune cells have a double-edged sword potential in treating neuronal injuries, Prof. Schwartz explains. The key to using them effectively is to extract the cells from the patient’s blood and increase their amount and activity in such a way that their healing effect is maximized while their potential risk is minimized; the cells are then reintroduced into the damaged neuronal area (this is the current approach for helping spinal cord repair). Another alternative would be to harness the cells’ potential by appropriate vaccination (the approach currently developed for chronic or acute neurodegenerative conditions). Prof. Schwartz: "The concept is to work together with the body’s existing self-repair mechanism, which apparently requires encouragement and monitoring."

Yeda Research & Development Co. Ltd., the Weizmann Institute’s technology transfer arm, filed patents for Prof.Schwartz’s findings. In order to promote this research and develop it further for possible clinical use, Yeda has entered into a licensing agreement with Proneuron Biotechnology Inc. a start-up company located in the Kiryat Weizmann Industrial Park, adjacent to the Institute.

Prof. Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel. Its 2,400 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science.

Weizmann Institute news releases are posted on the World Wide Web at, and are also available at

Proneuron BioTechnologies

Proneuron is currently focusing its expertise in cell therapy and neuroimmunology on the development and commercialization of a treatment for spinal cord injuries (SCI) as well as other neurological disorders, which until now were considered incurable.

The Company was founded in 1996 based upon the groundbreaking research of Professor Michal Schwartz of the Weizmann Institute of Science, who demonstrated the role of immune response in normal and pathological conditions in the CNS. Proneuron is determined to establish itself as a fully integrated company that will independently develop and commercialize therapies for niche CNS disorders

Scientific Rationale

Proneuron adopted a unique and novel approach to attenuate neuronal loss by employing the body’s own machinery of protection and repair via the immune system. The body routinely employs the immune system to protect against intruding microorganisms (such as bacteria and viruses) by attacking and eliminating them. Following tissue damage, the immune system plays a major role in wound healing and regeneration by eliminating toxic elements, clearance of dead cells and secretion of trophic and growth factors. For the CNS, which is an immune-privileged site, the common wisdom has been that any immune activity should be limited and if it does exist, it is detrimental.

The work of Professor Schwartz, supported by others, has suggested that in the context of the "suffering" CNS, the immune system plays a key role, provided that the activity is well regulated in terms of the type of activity (cell specificity and phenotype), onset, intensity, and duration. Any malfunctioning of the immune activity, harnessed by the suffering CNS, is likely to lead to a failure to display any benefit to the tissue or could even display a negative contribution. Prof. Schwartz has shown that appropriate modulation of the immune system can improve recovery and protect against chronic or acute neuronal loss in the CNS. As a result of these findings, her group has devised a novel form of therapy in which the natural activity of the immune system is harnessed to facilitate recovery after acute spinal cord injury and attenuate neuronal loss in a variety of neurodegenerative diseases.

Product Portfolio

To date, this approach has provided the Company with its lead candidate, ProCord™, which is an autologous activated macrophage therapy, currently in the process of applying for an FDA approval for a Phase 2/3 clinical trial for the treatment of complete SCI. Proneuron has completed enrollment of patients in the FDA approved Phase 1 clinical trial. The preliminary results suggest that the therapy is safe. Furthermore, it exhibited promising efficacy. Due to the significant unmet need in the area of SCI, the Company anticipates that the FDA will grant ProCord™ a "Fast Track" designation. The Company is also conducting a Phase 1b clinical study in collaboration with the Erasme Hospital in Brussels, Belgium, thus showing the successful transfer of the technology. This study is expected to complete enrollment of patients in 2003.

Proneuron has developed a number of additional products including a repertoire of proprietary therapeutic vaccines for acute and chronic neurodegenerative disorders. This repertoire includes 2 antigens (Cop-1 and PN277) which are in advanced preclinical development for various indications. Cop-1 uses Copolymer-1, the active compound in Copaxone® (Teva Pharmaceutical Industries Ltd. – Nasdaq: TEVA), which is an approved treatment for Multiple Sclerosis. During 2001, Proneuron entered into a strategic collaboration with Teva to develop and commercialize Cop-1 for various indications. Based on promising preclinical results and the proven safety profile of Cop-1, Proneuron is in the process of implementing an intensive development plan that may enable clinical studies in ALS and Huntington to commence during 2003.

Proneuron’s portfolio also includes a novel molecule, Immune Privilege Peptide (IPP), a molecule with strong immuno-modulating properties that occurs naturally in the brain. A future drug based on IPP may prove useful for treating inflammatory diseases and graft rejection, and is expected to have therapeutic utility in Multiple Sclerosis, Alzheimer’s Disease and Parkinson’s Disease.

Company Team

Proneuron benefits from its world-renowned scientific advisory board (SAB), led by Professor Michal Schwartz, incumbent of the Maurice and Ilse Katz Professorial Chair of Neuroimmunology, at the Weizmann Institute of Science in Rehovot, Israel. Professor Schwartz has published extensively on the concept of the cross-talk between the immune and the nervous systems in acute and chronic neurodegenerative disorders, most notably in peer-reviewed journals such as Nature Medicine and The Lancet. In addition, the company’s SAB benefits from the experience of numerous academic and industry experts, including: Prof. Edward Benzel, Director of Spinal Disorders in the Department of Neurosurgery, The Cleveland Clinic Foundation; Prof. Jacques Brotchi, MD, PhD, Professor and Chair of Neurosurgery, Universite Libre de Bruxelles; Prof. Charles H. Tator, MD, PhD, FRCSC, Professor and Chair of Neurosurgery at the University of Toronto; Prof. Howard L. Weiner, MD, Director of the Multiple Sclerosis Program Center for Neurological Diseases, Harvard Medical School.

The management of Proneuron is well positioned to address the challenges facing the company. The management team consists of: Dale S. Miller- Executive Chairman, Prof. Michal Schwartz – Scientific Founder, Nir Nimrodi – Chief Executive Officer, David Snyder, PhD – VP Clinical Development, Eti Yoles, PhD – VP Product R&D, Jeremy Rome, CPA and MBA – VP Finance.

Dr. David Snyder, VP Clinical Development
Proneuron Biotechnologies, Inc.
US office: 1801 Century Park East, Los Angeles, CA 90067, USA
Israel Office: P.O.B 277, Ness Ziona, 74101, Israel
Tel. +972-8-9409550, Fax. +972-8-9409560
Web site:

Alyn Pediatric Hospital and Rehabilitation Center for Physically Handicapped Children

Alyn Hospital is the only pediatric and adolescent rehabilitation center in Israel. The hospital offers the full spectrum of rehabilitation services to Jewish and Arab children in need, utilizing a multi-disciplinary approach and innovative techniques tailored to each individual patient. Patients are referred to Alyn from around the country with a wide spectrum of diagnoses, ranging from congenital abnormalities and complications of prematurity to cerebral palsy, muscular dystrophy and post-traumatic brain or spinal cord injury. In particular, the hospital has a special focus on respiratory rehabilitation, with a 19-bed respiratory rehabilitation unit dedicated to enabling ventilated and/or tracheostomized children to successfully rejoin their families at home.

In the Respiratory Rehabilitation Unit, Christopher Reeve met with 4 patients:

1) N is a 7 year old Jewish girl from the Negev who was involved in a motor vehicle accident 3 years ago and sustained a broken neck. Her injury is identical to that of Christopher Reeve’s, and she is permanently ventilated via a tracheostomy. She completed a full period of rehabilitation at Alyn 2 years ago, and is now mobile in her wheelchair and attends Alyn’s school for children in need of medical supervision.

2) D is a 6 year old Arab girl from East Jerusalem who was born with a congenital disorder causing contractures of all her joints and ribs. Although she is unable to move her body at all and is permanently ventilated, she is a very bright and inquisitive child who participates actively in her nursery school class at Alyn. She lives at home with her parents, and comes to Alyn daily for her educational and medical needs.

3) R is a 23 year old girl of Druze origin, who was injured in a motor vehicle accident 7 years ago, sustaining a fractured neck. After undergoing a full course of rehabilitation therapy at Alyn, she was discharged home 5 years ago. She is now able to walk with the aid of a walker, and use her hands functionally. When first admitted to Alyn she was ventilated through a tracheostomy, but has since been weaned of off ventilation, and has had her tracheostomy removed. R is currently admitted at Alyn for a 2-week rehabilitation "booster".

4) C is a 4 year old Jewish boy from Afula who was born with severe congenital weakness of all his muscles. As a result, he uses a ventilator at night, and requires a wheelchair for mobility. He was transferred to Alyn from the neonatal ICU at Afula Hospital, and during his admission here he underwent intensive rehabilitation therapy while his parents learned how to take care of him at home. He has since been discharged from Alyn, and is making excellent progress at home with his family.

In addition, Christopher Reeve met with 2 patients in the new "Independent Residential Complex". This is an innovative project aimed at providing adult patients on full-time ventilation the opportunity to live independently in private apartments, while still having access to the medical/nursing support of the hospital respiratory service. While this complex is located on the premises of Alyn hospital, it is an independent neighborhood, designed around a "pedestrian mall" theme, and is intended for long-term residential use by stable patients not in need of hospitalization.

1) O is a 19 year old girl who suffers from muscular dystrophy, a disease causing gradual and progressive weakening of all the muscles of the body. As a result of her condition, O is paralyzed in all 4 limbs, is wheelchair-bound, and is permanently ventilated via a tracheostomy. Despite this, she has a bright and vivacious personality. She will soon be moving into the Independent Residential Complex.

2) Y is a 21 year old with Duchenne Muscular Dystrophy, who lives at home. He is fully paralyzed and wheelchair bound, and has been on mechanical ventilation for the last 2 years. Despite his need for full-time ventilation, Y does not have a tracheostomy, and is ventilated in a completely noninvasive manner. This method of ventilation enables patients to completely avoid the need for tracheostomy, and Alyn is the only hospital in Israel with expertise in this technique.