06/20/2012 07:46 am ET

Stem Cell Clinical Trials Suggest Highly Touted Medical Technology Is Headed For Prime Time

By Dennis Normile

YOKOHAMA, JAPAN—For more than a decade, stem cell therapies have been touted as offering hope for those suffering from genetic and degenerative diseases. The promise took another step toward reality last week with announcements here at the annual meeting of the International Society for Stem Cell Research (ISSCR) that two groups are moving forward with human clinical research, one focusing on a rare genetic neurological disease and the other for the loss of vision in the elderly.

StemCells Inc. of Newark, California, reported encouraging results of an initial human trial using human neural stem cells to treat Pelizaeus-Merzbacher disease (PMD). PMD is a progressive and fatal disorder in which a genetic mutation inhibits the normal growth of myelin, a protective material that envelopes nerve fibers in the brain. Without myelin, nerve signals are lost, and the patient, usually an infant, suffers degenerating motor coordination and other neurological symptoms. In her presentation, Ann Tsukamoto, StemCells' vice president for research, said the company chose to test its neural stem cell approach on PMD because there is currently no treatment for the condition and a diagnosis can be confirmed by genetic testing and magnetic resonance imaging. "This creates an opportunity for early intervention when it can best help."

The company has created banks of highly purified neural stem cells that are isolated from adult neural tissue. Injected into rodents, the cells don't form tumors; rather, they migrate through the animals' brains, where they differentiate into various types of neural cells including the cells that create the myelin that protects nerve fibers. When neural stem stems were injected into in mice, they showed "robust engraftment and migration, the formation of new myelin," Tsukamoto said.

The company has now sponsored an initial safety trial of the strategy in four infants with PMD. In each patient, researchers at University of California, San Francisco, transplanted 75 million neural stem cells into each of four sites in the brain and followed that with immunosuppressive therapy so the recipient wouldn't reject the foreign cells. No safety concerns arose during the trial, Tsukamoto reported. Moreover, magnetic resonance imaging taken 18 months later indicated the formation of new myelin around axons and clinical observations of the treated patients indicated that their motor functions remained stable or enjoyed modest gains. The company is now planning larger trials. Tsukamoto says that if the therapy proves efficacious it could lead to neural stem cell treatments for multiple sclerosis, cerebral palsy, and Alzheimer's disease.

In a second talk at the meeting, stem cell researcher Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe reported on progress in her group's preclinical work targeting wet-type age-related macular degeneration (AMD). In AMD, the retinal pigment epithelial (RPE) cells that support the cells in the eye that detect light wear out, and there is also the growth of abnormal, leaky blood vessels below the retina. These conditions lead to impaired vision in the central part of the eye. Her group's proposed strategy is to surgically remove the problematic blood vessels and replace the damaged RPE cells with new RPE cells derived from a patient's own cells. Using a process called cellular reprogramming, the researchers take a patient's skin cells, convert them into so-called induced pluripotent stem (iPS) cells, which can differentiate into all the cells within the human body. They then transform those iPS cells into RPE cells and form them into sheets in the lab. Since the iPS approach uses the patient's own cells, they avoid the need for immunosuppressive drugs.

The RPE cells generated by Takahashi's team show the characteristic structure and gene expression pattern of authentic human RPE cells. Injections of the cells into mice triggered no tumors, she also reported, and the cells survived for more than 6 months when transplanted into monkeys. The research team has not directly tested whether the transplanted RPE cells improved the animal's vision. But Takahashi notes that some people with AMD have had RPE cells transplanted from the periphery to the center of their eyes, improving their central vision. She hopes to have all necessary approvals for research with human subjects within a year.

Earlier this year, scientists at University of California, Los Angeles, and Advanced Cell Technology of Marlborough, Massachusetts, reported in The Lancet about the safe and successful use of RPE cells derived from human embryonic stem cells, rather than iPS cells, to treat a different type of AMD in a limited number of human patients. Takahashi predicts that in the future, selecting from different stem cell therapies will "depend on the target disease and the situation of the host."

The positive results reported in The Lancet paper and presented at ISSCR will help the field "gather momentum," says Fiona Watt, a stem cell researcher the Cancer Research UK Cambridge Research Institute. And George Daley, a stem cell scientist at Harvard Medical School in Boston, is even more upbeat. Noting the progress reported at this year's conference, he says, "Wait until next year in Boston," the site of the 2013 ISSCR meeting.

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