Proneuron’s treatment involves isolation of macrophages from the patient’s blood, processing in the laboratory and then injection of the cells into the spinal cord in the vicinity of the area of damage.A revolutionary experimental therapy for spinal cord injuries is being developed by Proneuron Biotechnologies, Inc based on discoveries made in Israel at the Weizmann Institute of Science.

The therapy, recently completed Phase I FDA approved clinical studies, demonstrated preliminary promising results with the first patients. With these results, the company is expecting the U.S. Food and Drug Administration (FDA) to approve plans for Phase II testing of the therapy to begin in late summer in the US.

Proneuron’s treatment involves isolation of macrophages from the patient’s blood, processing in the laboratory and then injection of the cells into the spinal cord in the vicinity of the area of damage. The treatment, which must be provided within 14 days of spinal cord injury, requires a surgical procedure to open the spine for the injection of the macrophage cells into the spinal cord.

During his fact-finding visit here last week regarding Israel’s work in the field of spinal cord injury therapy, American actor Christopher Reeve met with the directors of Proneuron, and expressed amazement at the technology and the results.

Having first obtained the approval of the FDA and the Israeli Ministry of Health, Proneuron began the first Phase 1 clinical trial in July 2000 and reached the target recruitment of 8 patients in February 2002. All the patients had suffered a spinal cord injury in the previous 2 weeks and as a result had lost completely the motor and sensory nerve function below the level of the injury. Spinal cord injuries of this type are termed “complete”, or “ASIA A” according to the scale developed by the American Spinal Injury Association.

The results for the first eight individuals who received this experimental therapy in Israel were reported at the National-International Neurotrauma Society Meeting in Tampa, Florida., last October. Three of the original eight individuals experienced some recovery of both sensation and voluntary movement in their trunk and legs; recovery of this extent is very rare in patients with similar injuries.

Proneuron, a Delaware company, owns and operates a fully owned subsidiary in Ness Ziona, Israel, was founded in 1996 based upon a demonstration by Prof. Michal Schwartz and her team at the Weizmann Institute of Science that activated macrophages promote nerve regeneration and induce neuroprotection in the damaged spinal cord of laboratory rats. They provided the research basis for the development of the human clinical program.

“The technology is based on the individual’s own potential within his immune system. It’s a revolutionary approach to using the immune system,” Dr. David Snyder, Vice-President of Clinical Development at Proneuron, told ISRAEL21c. “We licensed the technology from Weizmann and have turned the idea into an application. And we’re in the process of bringing it to the clinic.”

The Phase I trials included patients from around the world who were flown to Israel for treatment and follow up – including patients from Holland, Mexico, Poland, and the U.S.A.
“It tells you something. doctors from all over the world sent their patients to Israel for a month – in the middle of this conflict – and that the families of the patients also came. From a patient perspective – there are no clinical alternatives,” said Snyder.

“We had actual success in the Phase I trials – which is an uncommon result – most Phase I trials deal more with safety and procedure,” explained Snyder. If a patient is completely tetra or parapeligic, there’s a very minimal chance of any kind of recovery, maybe 4%. Our trials showed 38% recovery. Patients who otherwise would have remained tetra or parapeligic can now either walk, with the aid of braces, and have control over their bladder and bowels. It’s a tremendous story.”

During his visit, Reeve viewed a video made by Melissa Holley, an American spinal cord patient who was involved in the Proneuron Phase I trial, in which she talked about her treatment and her partial recovery. Holley was paralyzed from the chest down after a road accident in Colorado. In the wake of the treatment she has regained feeling below the injury, has the ability to move her toes and some leg muscles, and is learning to walk with crutches and braces.
Reeve also met two Israeli patients who were involved in the trials who also regained partial movement. According to Snyder, Reeve said it was incredible he was speaking to patients that had received therapy and who had been helped.

Dr. Daniel Lammertse, Medical Director of Craig Hospital in Colorado and former President of American Spinal Injury Association, has followed the clinical progress of several of the phase one trial subjects. He has also expressed a cautious optimism for the potential of this treatment: “The Phase I results suggest a positive treatment effect, giving clinicians hope that a new era of intervention is at hand.”

According to Snyder, the Phase II trials will take place at least at three locations in the U.S., and at Sheba Hospital in Israel. He explained that this is a complicated process because the cells need to be harvested and treated at the site where the patient is being treated.

“The cells need to be injected freshly back into individual soon after completing the treatment process. This means that a cell processing center needs to be built next to the treatment center,” Snyder said. “We’re in the process of presenting the details of the Phase II plan to the FDA – and by the end of the summer three centers will hopefully be up and operating in the U.S.”

One new cell processing center is currently being established at the Craig rehabilitation center in Denver, Colorado. The Craig Hospital has allocated the necessary space for Proneuron to establish its cell center and the BIRD Foundation (a Bi-national US and Israeli foundation) has approved a grant in the sum of $1,000,000.

Another cell processing center will serve Mt. Sinai Hospital, Manhattan and the Kessler Institute, NJ. These institutions have already been involved in the post-treatment care of the Phase I patients. The 3 US sites mentioned above have one thing in common. They are all part of the national Model SCI System. There 16 model centers today and Proneuron shall strive to service as many as possible of these sites. Patients from other sites will optimally be treated at these model centers eventually.

Besides the macrophage therapy, Proneuron is developing therapies for other neurological disorders that are usually considered incurable. These other projects derive from more of Schwartz’s discoveries on how to harness the immune system to protect and repair the nervous system.