December 26th, Globe and Mail

A costly second chance for little Isaac
With Ontario now funding an expensive new treatment, a two-year-old is flourishing despite his rare disease, LISA PRIEST writes

LISA PRIEST
TORONTO -- He's not even three years old, but the words pulse oximeter roll off Isaac McFadyen's tongue, as if they are second nature. He knows the device well; it clips onto his finger and measures the oxygen in his blood. It's one of several checks done each hour he undergoes treatment for his rare disease.

But Isaac's life is not one of suffering. It is that of a preschooler thriving after receiving one of the most expensive drugs in the world -- Naglazyme -- the only treatment for Maroteaux-Lamy syndrome, an inherited metabolic disorder.

The bag of colourless medicine, not even a cupful, costs the public health-care system $5,000 to $6,000 for each weekly treatment, something he will require, in some form or another, for the rest of his life.

In the three months he has undergone enzyme replacement therapy, Isaac's parents say they've witnessed dramatic physical changes. Isaac has grown two inches and his belly, once rotund due to an enlarged spleen and liver, has shrunk by three inches.

"For us, the idea that he has a chance at a future, is more than we ever had before," Isaac's father, Andrew McFadyen, said.

During his 14th infusion in early December, Isaac, a high-spirited boy, rode a plastic tricycle in the corridors of Toronto's Hospital for Sick Children, as his mother, Ellen Buck-McFadyen hurried along with him, clutching the intravenous pole that carried his medicine.

A few months ago, the future looked bleak for Isaac, who has mucopolysaccharidosis type VI, or MPS VI for short, a disease so rare it's estimated that only three to 10 Canadians have it.
In May, his family faced moving to England where the drug is funded by government -- at the cost of $300,000 to $1-million annually -- or watch Isaac be ravaged by the inherited metabolic disorder.

He had already suffered some of the ill effects of the disease: a piece of his skull and a portion of vertebrae in his neck were removed after they began compressing his spinal cord. His corneas were clouding, his forehead protruded and he had an umbilical hernia.

"We were really close to moving," said Mr. McFadyen, who was eligible for British citizenship through his Welsh mother. "We had our application filled out and all set to go."

When Isaac's plight was profiled in The Globe and Mail in May as part of a broader piece on the lack of an organ drug policy in Canada, the story drew swift reaction, with the subject being raised twice in the Ontario Legislation by the opposition.

In July, the provincial government decided to fund the drug for Isaac after a clinical review by members of Ontario's inherited-metabolic-diseases program.

"This is not a cure but neither is insulin a cure for diabetes," said Joe Clarke, senior associate scientist in the Hospital for Sick Children's Research Institute, who has treated Isaac. "We're hoping that it will correct the metabolic abnormalities sufficiently so that the disease won't progress."

In developed countries, there are an estimated 1,100 sufferers, virtually all of whom will experience severe disability and shortened life spans. That's because those with MPS VI are missing an enzyme called arylsulfatase B, needed to break down carbohydrates known as glycosaminoglycans. The carbohydrate builds up in the body's cells and affects multiple organs.
Signs of the disease include stunted growth, enlarged tonsils and adenoids that cause breathing problems, poor mobility and dramatic changes in facial features, including a flat nose and large head. In their teens, sufferers often require heart-valve surgery.

"Isaac is the youngest patient I've ever seen with the condition, so we have to consider him to be programmed to have more severe disease," Dr. Clarke said. "The results we've achieved so far, I'm very, very happy with, ecstatic with it."

Although the drug won't necessarily reverse the damage the disease has already done, it will help halt its progression.

"If Isaac didn't get this drug, he was simply going to continue to progress where there would be very little in the quality of life for him," said Conservative health critic Elizabeth Witmer, who twice raised his plight in the legislature.

She is concerned about Canada's lack of an orphan drug policy, as is Durhane Wong-Rieger, president of the Canadian Organization for Rare Disorders.

"There is widespread agreement that we need to provide some treatment for rare disorders," Dr. Wong-Rieger said. "But there's no agreement on how we're going to provide the funding . . . There's some real urgency in terms of putting together a process to evaluate these drugs."
Since Isaac began receiving treatment in September, his life has turned around. The problems of today are much smaller than those of a few months ago: a traffic snarl as they make the two-hour drive to the hospital from their home in Campbellford or a puzzle piece that goes missing in the hospital playroom.

"It's such a huge relief," Ms. Buck-McFadyen said, holding her other son, 13-month-old Gabriel, at the hospital. "We know how fortunate we are."