The health ministry gave the go-ahead Feb. 18 for the world’s first clinical trial of human induced pluripotent stem (iPS) cells to treat spinal cord injuries, raising hopes for those with the chronic condition.

The study will be carried out by a research team at Keio University's graduate school of medicine in Tokyo headed by Hideyuki Okano, a professor of physiology, and Masaya Nakamura, a professor of orthopedics.

Four patients to be selected for the trial slated to start in autumn will have been diagnosed between two to four weeks beforehand as totally paralyzed with no mobility and sensory functions, the most severe form of spinal cord injury.

The clinical study aimed at recovering the patients' nerve functions was approved by a special committee of the Ministry of Health, Labor and Welfare.

More than 100,000 people in Japan are believed to suffer from spinal cord injuries, but treatment remains elusive. Rehabilitation at present offers the best option.

The team said it hopes to achieve practical results through the use of regeneration medicine based on iPS cells.

The individuals selected for the trial will be in what is known as the subacute phase, thereby offering a greater prospect of success compared with patients who were injured long ago.

Treatment will involve converting iPS cells into ones that serve as the base for neural cells, and transplanting the clusters into the patients.

Okano, in a news conference at Keio University Hospital in Tokyo's Shinjuku Ward on Feb. 18 to announce the trials, said it will take a year or so to confirm the safety and validity of the treatment, coupled with rehabilitation, once the first transplants of cells clusters have been performed.

Given that tumors are a potential side effect of the treatment using iPS cells, and therefore a major cause of concern, the team put priority on safety by deciding to use relatively small amounts of cells: 2 million cells for each transplantation.

As an added precaution against the patients developing tumors, team members plan to inject a chemical substance called GSI to treat the iPS cells prior to transplantation.

Immunosuppressive drugs are a standard treatment in trying to suppress the possible rejection of iPS cells derived from other individuals.

5,000 NEW INJURIES EACH YEAR

Each year, about 5,000 individuals are thought to suffer spinal cord injury in Japan.

The subacute phase lasts only for about six months after the onset of injuries, after which patients enter the chronic phase that is characterized by paralysis. Most patients of spinal cord injuries in Japan are in the chronic phase.

Makoto Ohama, who heads Spinal Injuries Japan, an association of people with spinal cord injuries across the country, said targeting patients in the subacute phase could raise hopes for those with a chronic condition.

“My hope is that regenerative medicine will also become available for patients with spinal cord injuries in the chronic stage as early as possible," Ohama said. "The first step is to confirm the safety of the treatment for those in the subacute phase.”

Patients who were injured within the previous six months, including those in the subacute phase, are deemed more likely to recover than those in the chronic phase due to scar tissue formed by the spinal cord injuries. The presence of such tissue makes the transplantation of iPS cell clusters difficult and hinders regeneration of nerve cells.

But the research team said that when GSI-added iPS cells are transplanted near an injured area of the spinal cord, nerve regeneration could become possible without removing scar tissue.

However, treatment for patients diagnosed as being completely paralyzed is extremely difficult, especially when they are in the chronic phase.

“Our aim is to start clinical studies two to three years from now on patients who retain part of their motor functions despite of being in the chronic phase,” Nakamura said.

Sumitomo Dainippon Pharma Co. teamed up with Keio Universty to develop the treatment for spinal cord injury.

“The onset of the clinical study (on the spinal cord injury treatment using human iPS cell-derived neural cells) is a giant stride,” said Toru Kimura, executive officer of Sumitomo Dainippon Pharma.

“Our ultimate goal is to commercialize iPS cell-derived neural cells for patients in the chronic phase.”

When to convert them into a commercial reality will be decided in light of how the clinical study progresses, Kimura added.

(This article was written by Masatoshi Toda and Roku Goda.)