End of clinical trial disappoints Parkinson's sufferer, his family

BY Anne Kelly

Philip Walker, record staff

CAMBRIDGE

A Cambridge man who might have benefited from a novel therapy for Parkinson's disease is disappointed that clinical trials have been halted.

Kees Vreugdenhil had adult eye cells injected into his brain 16 months ago in hopes of relieving some of his symptoms and helping advance research into Parkinson's.

The 70-year-old's sister and cousin also have a neurological movement disorder.

Vreugdenhil was excited to learn in August from Boston University Medical Center, where he was enrolled in the multi-site study, that he had actually received the treatment.

Half the 71 participants in the Phase 2 double-blind randomized trial had the treatment called Spheramine injected into both sides of the brain. The rest underwent what the researchers called a sham surgery, in which no cells were implanted.

The study was for patients with moderate to severe Parkinson's.

Vreugdenhil was told by his Boston doctor in August that the project was under review because results weren't as positive as hoped.

But he was surprised to learn recently that the pharmaceutical giant Bayer Inc., which had been partnering with Titan Pharmaceuticals on the trial, halted development of Spheramine in July.

"The STEPS trial with Spheramine did not show any difference in the outcome between the (sham surgery) and the actively treated patient groups," Adrienne Jackson, director of communications at Bayer Inc.'s Toronto office, wrote in an e-mail to the Waterloo Region Record.

Full results of the trial will be published in late December.

Vreugdenhil will be reading with interest.

"I was pretty hopeful that some positive result might come from this study," he said in an interview. "That appears not to be the case."

Vreugdenhil was given the option of continuing to go to Boston for monitoring, which he's decided to do.

The eye cells used in Spheramine are retinal epithelial pigment cells, which appeared promising for symptom relief because they produce levodopa.

Levodopa is a precursor to dopamine, a neurotransmitter that controls movement. In the brain, levodopa is converted to dopamine, which in people with Parkinson's is depleted because the neurotransmitters die.

It was hoped Spheramine would produce significant reduction in symptoms of the disease, which include tremor, muscle rigidity and stiffness, poor balance and slowed movement.

A Phase 1 trial with six patients showed promising results, and earlier results from Phase 2 were hopeful.

Dr. Mandar Jog, director of the Movement Disorders Clinic at London Health Sciences Centre, said placing dopamine-producing cells in a part of the brain where dopamine is missing makes sense.

"The science behind it is solid," Jog said. But the treatment was controversial because it involved expensive, invasive surgery that had the potential to help only a small segment of people with Parkinson's, he said.

Its lack of success won't be fully understood until results are published and peer-reviewed, Jog said.

Vreugdenhil decided to enrol after his daughter saw a newspaper ad for the trial in December 2006.

The delicate four-hour surgery to implant the cells was done at Emory University Hospital in Atlanta. Vreugdenhil is about to make his 14th trip to Boston University Medical Centre, where he has undergone two days of tests on each trip.

All travel expenses for him and his wife, Liz, are covered and they expect to make several trips to Boston over the next year or so for monitoring.

Although he noticed no improvement, Vreugdenhil doesn't feel it was a wasted effort.

"I have no regrets and would do it again if I had the opportunity," said the retired Union Gas executive, who was diagnosed in 1999. He is eager to advance scientific research into a disease he hopes will never afflict his children or grandchildren.

"I was willing to do anything to prevent them from getting it,'' he said. "It is my contribution to science. If there was something in it for me that would be wonderful."

While the goal of the eye cell therapy was symptom relief, not prevention, every Parkinson's experiment advances scientists' understanding of the degenerative disease.

"You always gain some knowledge and information," Liz said.

Vreugdenhil's symptoms began at age 55, with deteriorating handwriting and a weakening singing voice.

When his family doctor noticed a change in his facial expression in 1999, he suspected Parkinson's and had him tested.

Today Vreugdenhil experiences weakness, balance problems and a shuffling gait, which requires him to use a cane or walker. His face has a masklike appearance, typical of some people with Parkinson's.

He takes 17 pills a day.

"It's quite a fistful. I look at it every morning and say 'this can't be good for me.' "

Vreugdenhil previously participated in a study at Wilfrid Laurier's Movement Disorders Research and Rehabilitation Centre.

Between trips to Boston, he and Liz carry on with a busy life. The couple founded a Parkinson's support group after moving from Chatham two years ago to be near their daughter and raise funds for the Parkinson Society.