University Times

Surgeons at UPMC Presbyterian have performed the world's first cell transplant aimed at reversing brain damage from stroke.

During the June 23 operation, surgeons injected 2 million healthy, lab-produced human nerve cells deep into the brain of Alma Cerasini, 62, of Pennsbury Village.

Cerasini, a former healthcare worker, suffered a major stroke in September that left her right arm and leg paralyzed and took nearly all her ability to speak.

She went home the day after the three-hour surgery and is doing well, doctors said at a July 1 news conference. But it's too soon to tell if the new cells will restore her ability to speak or move her right side, they noted.

Cerasini's responses will be watched carefully. If the neuronal transplant is found to repair some damage, it will provide hope for many of America's 3 million stroke survivors.

Stroke is the third leading cause of death and the most common cause of adult disability in the United States, according to the National Institutes of Health. Each year, 700,000 Americans suffer a stroke; 30 percent die and 20-30 percent become severely and permanently disabled. Annual costs to society are estimated at $41.9 billion.

Currently, rehabilitation through physical and occupational therapy is the only treatment available for stroke patients. No treatment has yet been proved to be effective in reversing neurologic damage months after the stroke.

"This trial opens the door to fuller recovery from stroke. While physical and occupational therapy helps many patients adapt to the damage their brain has suffered from stroke, neuron cell transplantation may allow patients to recover lost abilities," said Douglas Kondziolka, Cerasini's surgeon, co-principal investigator for the FDA-approved study and a Pitt professor of neurological surgery and radiation oncology.

"This treatment at least offers the hope we will someday be able to help people months, perhaps years after a stroke has occurred," said Lawrence Wechsler, co-investigator of the study and director of the UPMC Stroke Institute.

The treatment could even be modified to treat Parkinson's, spinal cord injuries, epilepsy and other localized neurological disorders, Kondziolka said. "This is what we've been waiting for, well, forever," he told reporters.

Use of manufactured cells to reverse brain damage removes ethical concerns about transplanting fetal tissue, the investigators pointed out.

The FDA has approved the neuron transplant study only at UPMC. As a phase I trial, its primary goal is to test the therapy's safety. Future studies will focus on its effectiveness.

Twelve patients will participate in the phase I trial. The next two patients, one each for surgeries scheduled in July and August, have been chosen. Participants must be 40-75 years old and have suffered strokes six months to six years ago that struck the basal ganglia area of the brain, causing paralysis.

Neurons used in the UPMC transplants are provided by Layton Bioscience, Inc., of Atherton, Calif. The LBS neurons, as they're called, came from a teratocarcinoma tumor found in a 22-year-old cancer patient. Teratocarcinomas are tumors of the reproductive organs that are composed of embryonic-like cells. Layton Bioscience has patented a process that uses chemicals to transform the rapidly dividing cell line into fully differentiated, non-dividing neurons that are safe for clinical use.

In preclinical testing, transplants of LBS neurons reversed cognitive and motor damage in animals in which stroke had been induced, UPMC officials said.

The transplant procedure in humans begins with placement of a stereotactic frame on the patient's head. CT or MRI scans are taken to enable surgeons to see dead tissue inside the brain.

After doctors thaw neurons that were frozen and transported from Layton Bioscience, they count the cells to ensure there are at least 2 million viable ones to transplant. Then they transfer the cells to a long-needled syringe. A surgeon injects these cells through a small hole drilled through the skull. The needle is removed and the opening closed with one stitch.

Participants will receive MRI scans and other screenings, as doctors look for neural activity at the transplant site, as well as side effects. Patients receive the anti-rejection drug cyclo-sporine for one week prior to surgery and for two months after.

— Bruce Steele