Taken from unrelated donors, doctors are saving the lives of children with Hurler's syndrome — a rare congenital illness that typically kills victims before they reach the age of five.
While experts have been treating Hurler's syndrome with stem cells taken from bone marrow for years, the use of cells derived from cord blood improves treatment while helping children avoid painful and debilitating radiation therapy, researchers say.
"It's ameliorating all the symptoms," said study co-author Dr. Joanne Kurtzberg [dir, Pediatric Bone Marrow and Stem Cell Transplantation program, Duke University's Comprehensive Cancer Center]. Her team's findings appear in the May 6 issue of The New England Journal of Medicine.
Experts estimate that between 40 and 100 American children are born annually with the metabolic disease mucopolysaccharidosis type 1 (MPS-1), commonly called Hurler's syndrome. The syndrome leaves children unable to produce an important enzyme known as alpha-L-iduronidase, crucial to the breakdown and recycling of cells that have outlived their usefulness.
As a result, unrecycled cells gather in various body sites, resulting in damage to bones, liver, spleen, corneas, cartilage and even the brain. Children affected by Hurlers typically suffer from slowed growth and mental retardation. Left untreated, the illness is usually fatal by age five.
However, in the early 1980s doctors began making real headway against Hurler's. They discovered that transplanted stem cells derived from human bone marrow allowed affected children to begin to produce small quantities of the much-needed enzyme. Still, treatment hurdles remained.
As with all transplants, "some patients who need a donor can't find a close enough match," Kurtzberg said, so about 50 percent of Hurler's patients died before finding a suitable donor. Of those to receive transplants, about a third experienced immune-system rejection of the transplanted cells.
Stem cells sourced from umbilical cord blood offer patients more hope, Kurtzberg said, because they are at a more immature stage of development. This means that cord blood stem cells "do not have to be matched so closely, and patients who can't find a match in bone marrow can find suitable cells in cord blood," she added.
Stockpiles of life-saving umbilical cord blood is now being collected and stored at special cord blood banks across the country.
In their study, the Duke researchers performed cord blood stem cell transplants in 20 Hurler's children under two-and-a-half years of age. So far, 17 of the 20 children have survived for more than three years after transplant, and most have shown remarkable reductions in symptoms, according to the study.
Kurtzberg said, "It looks as if kids who get the cord blood transplant have less chance of the disease in the brain and outside the brain," compared to children who received stem cells derived from marrow.
"Their bones are healing better, their I.Q.s are rising faster," she said. It's the benefit to children's cognitive abilities that excites the researchers the most, since "in the bone marrow transplants, the kids remain mildly mentally compromised. But in these kids that we are doing the cord blood in, their I.Q.s were actually returning" to levels closer to normal, Kurtzberg said.
The researchers speculated that stem cells from cord blood may be better than other agents at transporting alpha-L-iduronidase across the blood-brain barrier, effectively reducing or reversing brain damage.
There's one other benefit to the new therapy: because risks for immune-system rejection are much lower with cord blood stem cells, many children are spared immune-suppressing radiation therapy, according to the study.
"We felt that was very important in this disease because radiation therapy causes later damage to the brain and we didn't want to add to a problem that children already had based on the disease itself," Kurtzberg said.
Barbara Wedehase is a genetic counselor and executive director of the National MPS Society, which works on behalf of families affected by Hurler's syndrome and similar enzyme-deficiency disorders. She said research into stem cell therapy and other treatment options is "offering us tremendous hope" in battling what was once a uniformly terminal illness. Wedehase stressed that while cord blood stem cell therapy marks a breakthrough in fighting Hurler's, it is most valuable in very young children.
"If the transplant is done in children with MPS 1 under the age of 2, there's a very good likelihood that there will be a preservation of intelligence," she said. "If, however, the transplant is done with children older than that, neurological disease progresses."
She said parents often face great "emotional distress" when they learn their child has any of the dozen or so MPS-related syndromes. "I encourage families not only to talk with the specialists who are doing these procedures," she said, "but to talk with other families who may have chosen to have had a particular procedure, as well as those who've chosen not to, so that they get as much information as they can before they make their decision."
Information for fighting MPS syndromes can be found at the National MPS Society (www.mpssociety.org ). For more on donating cord blood, visit the National Marrow Donor Program (www.marrow.org ).
[Joanne Kurtzberg, M.D., director, Pediatric Bone Marrow and Stem Cell Transplantation program, Duke Comprehensive Cancer Center, Durham, N.C.; Barbara Wedehase, genetic counselor, and executive director, National MPS Society, Bangor, Maine; May 6, 2004, New England Journal of Medicine ScoutNews, E.J. Mundell, May 5 (HealthDayNews) http://www.klkntv.com/Global/story.asp?S=1844509; Nancy ValkoRN, 18Aug04]