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Enzyme replacement therapy gives children hope

OAKLAND Beating early death: Enzyme replacement therapy at Children's Hospital conquers a genetic disorder that often kills many young sufferers before they reach 20
Erin Allday, San Francisco Chronicle
Published 4:00 am, Tuesday, May 20, 2008


  • - Photo: Noah Berger
    - Photo: Noah Berger


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Isabel Bueso has a rare disease that kills many kids before they hit their 20s. She traveled 2,500 miles from her native Guatemala to Oakland for an experimental new treatment to save her life. But she never considered herself particularly heroic.

That changed when she met the babies with her disease. Isabel's treatment may mean that they and thousands of other children never have to endure the worst symptoms of mucopolysaccharidoses, a genetic disease that often causes young sufferers to stop growing and can lead to a variety of disabling side effects, including blindness and nerve damage from extra pressure in their skull or spinal column.

"At first I felt like this was a big adventure," said 12-year-old Isabel of her trip to Oakland. "Now I have little kids like Amro and Jeffrey to look out for. I'm not really doing anything, getting this treatment. But I still feel proud of myself."

Oakland Children's Hospital has become a hub of research and community for kids like Isabel and the babies Amro and Jeffrey, who all suffer a form of mucopolysaccharidoses.

MPS, as it's called, is a family of diseases caused by enzyme deficiencies. Only a few thousand people in the world have MPS, and many sufferers can go their whole lives without ever meeting another person with the disease.

So it's remarkable that Oakland has become a bit of an enclave for MPS patients, say the children and their parents, almost all of whom uprooted from countries outside the United States, giving up jobs and school, friends and extended families for a life-saving treatment.

Isabel among the first

Oakland Children's Hospital is one of only three or four places in the world where a new enzyme replacement therapy is available. Isabel was among the first to get the therapy five years ago - she not only had to leave her home and her extended family, but brave an experimental treatment with unknown side effects.

The initial treatments went so well that the enzyme therapy won U.S. approval in 2005, and now researchers are testing it in babies.

The enzyme replacement therapy started in late 2000, when researchers from BioMarin, a Novato-based pharmaceutical company, approached Dr. Paul Harmatz at Oakland Children's Hospital about setting up a clinical trial for a form of MPS. Harmatz, who leads the hospital's research division, agreed to help and started recruiting patients from around the world.

Three clinical trials have been conducted at Children's Hospital since then - the most recent one, involving children under a year old, started last year and will continue at least another year. Because MPS is so rare, only five or six patients are involved in each study. The first drug studied, called Naglazyme, was approved by the U.S. Food and Drug Administration in 2005.

Almost all of the patients involved in the first clinical trial are still being treated in Oakland, coming to Children's Hospital every Friday for IV therapy.

"It's not really a cure, not like gene therapy might be someday. They have to come in every week because the enzyme is metabo- lized over a week's time," Harmatz said.

That means the families are stuck in the Bay Area, at least until the therapy becomes more widely available. For now, the nurses, doctors and other patients at Children's Hospital are the closest many children and their parents have to an extended family.

"We are forced to stay here. We gave up so much. But it was a clear decision to make for our daughter's life," said Isabel's mother, Karla Bueso. "I'm doing what any parent would do."

Isabel's doctors say the enzyme therapy has already improved her health and stalled some of the worst effects of the disease.

How MPS develops

In MPS, the body lacks an enzyme that prevents cells from breaking down chains of sugar called mucopolysaccharidoses. These sugar chains build up in all of the body's cells, which not only disrupt cell performance, but can lead to dangerous stashes of extra sugar in bones and cartilage.

There are at least seven different kinds of MPS, and not all of them respond well to enzyme replacement therapy. In particular, children who suffer brain damage from the missing enzyme are difficult to treat because the enzyme replacement drug has a hard time breaching the blood-to-brain barrier.

But for children like Isabel, the results have been dramatic. Isabel is still very small for her age, and the enzyme replacement isn't likely to reverse the damage already done to her bones. But she rarely suffers from the pain or respiratory infections related to MPS. Her tracheostomy tube - inserted three years ago to help with breathing when her trachea became constricted - was removed last year.

Her vision has improved, and she has more energy. She is able to ride her bike again.

"I can run faster and I can jump," Isabel said. "I couldn't really walk much before, because I'd get tired. Now I can walk all I want."

Other children have seen similar results, said Harmatz. Patricia Espinal, 16, grew 4 or 5 inches after receiving the therapy. Her brother, Harold, started walking again.

Now the therapy is being tested on the youngest MPS patients, the babies Isabel is watching: Amro, whose family lives in the West Bank, and Jeffrey, whose mother already lost one child to MPS.

Amro and Jeffrey have not yet shown serious, irreversible symptoms of MPS. Doctors are hoping they can keep them healthy for the rest of their long lives.

"It's hard to tell how they'd be doing if we weren't treating them," Harmatz said. "Someone like Amro, he probably would stop growing at 3 or 4 years old. If he keeps growing, we'll know it's working."

Online resources

Information about MPS can be found at:




Frequently asked questions about MPS

Q: What is MPS?

A: MPS, or mucopolysaccharidoses, is a family of genetic diseases marked by the body's inability to produce certain enzymes. These enzymes are used to break down chains of sugar, and without the enzyme, the sugars build up in cells, causing a variety of disabling symptoms.

Q: What are the symptoms?

A: Symptoms typically appear by the time a child is 2 or 3. Children have bone deformities, such as clubbed feet or curvature of the spine. They stop growing when they are very young. They also may experience pain in the bones and joints, and may be unable to walk. MPS can also cause blindness and brain damage in some forms.

Q: What is the long-term prognosis for MPS?

A: It depends on the form. Children with a type of MPS called Hurler syndrome often die before age 10. Patients with Scheie or Hunter syndrome can live into their 50s. Most children will die before their 20s.

Q: What treatments are available?

A: So far, enzyme replacement therapy, which is being clinically tested at Oakland Children's Hospital, has shown the most promise for many forms of MPS. Bone marrow transplants have been successful in some patients, but it is often difficult to find an acceptable match. Researchers are hoping gene therapy will offer a cure for MPS someday.