A Girl Without Bones

New drug gives growth to girl born with no bones


Child now has a skeleton strong enough for her to dance after experimental drug therapy.

Nurses didn't know a breakthrough drug was on the horizon when they dressed the tiny little girl in a pink outfit for a hospital photographer to take her picture.

It was a photograph for her parents -- an image of solace so they could remember Janelly Martinez-Amador free of tubes. Doctors told them then there was nothing more they could do for a child without bones.

Born with the most severe form of hypophosphatasia -- a genetic disorder that prevents skeletal mineralization -- the girl didn't have the ribs to support breathing. Her parents, Salvador Martinez and Janet Amador of Antioch, were facing the prospect of having to decide whether to continue life-sustaining interventions.

But Janelly held on long enough for a last chance at life. At age 2 years and 8 months, she entered a clinical trial involving an experimental medicine at Monroe Carrel Jr. Children's Hospital at Vanderbilt in Nashville. Four years later, Janelly can dance.

One of 11 children worldwide enrolled in the clinical trial, she was the runt of the bunch. Her disease was so pronounced she could not move her body. Her bones didn't even show up on X-rays. She was also the youngest and technically didn't meet the trial's 3-year-old age requirement.

But Vanderbilt physicians had been telling Dr. Michael P. Whyte, a metabolic bone disease specialist with Washington University School of Medicine in St. Louis, about Janelly.

Whyte was about to start a clinical trial for a new drug, a biologic enzyme called asfotase alfa, that he wanted to try on toddlers with hypophosphatasia. Although this genetic disorder can cause a wide spectrum of bone loss in people of all ages, patients diagnosed as infants like Janelly have the most severe form. They usually die.

Janelly was diagnosed at about 4 months old.

"We started noticing she wasn't growing as she should at that point, and she wasn't gaining the weight as she should at her age," Martinez said with the aid of a Spanish interpreter.

The baby responded to hugs as if in pain.

Pediatricians thought Janelly might have cancer when they sent her to the Vanderbilt hospital. Vanderbilt diagnosed the severe form of hypophosphatasia -- a rare disorder that occurs in only one of every 100,000 infants.

Complications from the disease worsened to the point that Janelly spent months in the intensive care unit before her first birthday. She had to get a tracheotomy and depend upon a ventilator to live. When her parents brought her home from the hospital, they also took home a ventilator.

They held onto to hope for a cure.

In February 2009, Janelly began treatment with a medicine that had been developed by Canada-based Enobia Pharma Corp. and put on fast-track approval status by the U.S. Food and Drug Administration because it was an "orphan drug" -- the first possible treatment for a disease. Shriners Hospitals for Children and Enobia, which has since been acquired by Connecticut-based Alexion, funded the clinical trial.

Janelly had a special port surgically inserted in her abdomen so she could receive infusions of this bone-targeting enzyme.

One of the 11 children in the trial started showed skeletal improvements as early as three weeks into treatment. All the others had "striking" skeletal healing by six months -- except for Janelly.

"We were fearful that her bone disease was so terribly severe that it might not work," said Whyte, who had never met Janelly but had read her case history when he enrolled her in the study.

Her parents were the first to notice a change. They saw her gaining muscle control before medical imaging detected bone growth. Doctors initially were discouraged.

"We kept hearing from all the other sites that patients were having significant improvements," said Dr. Jill H. Simmons, a pediatric endocrinologist at Vanderbilt children's hospital. "We kept getting skeletal surveys and seeing no evidence of calcification. We really weren't seeing any improvements in her for six months."

Although no one could see it, the enzyme was sticking like snowflakes falling in darkness.

"We were very concerned when the therapy started that there was no mineral in her bones to target with enzymes," Whyte said. "So, would the enzyme find its way to bone and hook onto something to help her? But apparently -- although you couldn't see the mineral on an X-ray, you didn't see any bones on X-ray -- there was still enough there that the first molecule or enzyme to land did something."

After almost a year of treatment, Janelly finally was able to move all her limbs. After 18 months of treatment, doctors could see ribs forming.

"It was literally within those few weeks that her pulmonologist really started to notice significant improvements and was able to back her off on a ventilator," Simmons said. "It was fascinating how the calcification of those ribs really significantly turned her around."

These days, Janelly darts around in a stroller, sits up to watch television and rolls across the carpet. She dances as gracefully as any ballerina, interpreting the music with hand movements, from her stroller. Although she will soon turn 7, she's still the size of a toddler. Her bones have just begun to grow.

The tracheotomy tube prevents her from talking, but she makes noises and responds to stimuli. She goes to Harris-Hillman Special Education School. The long-term effect on her learning ability from the delay in her physical development remains a mystery.

Janelly recently went back into Vanderbilt to have the port removed from her abdomen. Instead of intravenous infusions, she has grown big enough to receive the enzyme treatment via three shots a week.

This month, Whyte traveled from St. Louis to Nashville, where he met Janelly for the first time.

"Her fingers, can I feel them?" he asked her parents, before caressing Janelly's hands to find the tiny bones.

Tidak ada komentar:

Posting Komentar