Sept. 24, 2009 — -- Chris Woods, 44, of Merrimac, N.H., had gone to New Orleans in September 2005 for a month to volunteer following the destruction in the wake of Hurricane Katrina, when the right side of his body began to feel odd.
"There was stiffness in my right arm and hand. Pain and tingling in my right foot," Woods recalled. "It was getting worse rapidly."
Over the course of several months, Woods' doctors considered Lou Gehrig's disease, multiple sclerosis, and a brain tumor as causes for his symptoms before a writing test forced him to face an unwelcome diagnosis.
"When I write with my right hand, my right leg shakes," Woods said.
His neurologist diagnosed Woods, then 41, with early Parkinson's disease, a chronic neurological condition that worsens over time, causing tremors, stiffness and problems with balance and coordination and affects over 1.5 million people in the U.S.
"I guess I knew what was happening, but I didn't know it was connected [to Parkinson's], but it's a telltale sign," Woods said.
While there are several treatments that keep the symptoms of Parkinson's disease at bay, none have been shown to affect the underlying cause of the disease. Now, final results from a closely watched trial of the drug rasagiline (Azilect) in Parkinson's cases suggest the drug may slow patient deterioration, study leaders said, but some outside experts voiced doubts.
"It's the single most important study of the last decade for Parkinson's patients," said Dr. C. Warren Olanow, professor of neurology at the Mount Sinai School of Medicine and the principal investigator of the trial. "It's the first time we've defined a drug that looks like it is disease modifying -- it slows the rate of disease progression."
The 18-month study, called ADAGIO (Attenuation of Disease Progression with Azilect Given Once Daily), randomized 1,176 patients with untreated, early-stage Parkinson's disease into two groups, one that received rasagiline immediately and a second that received rasagiline after nine months.
Parkinson's Patients Slow in Disease Progression At 1 MG Rasagiline
Patients in the delayed start group receiving 1 mg per day of rasagiline showed a greater level of disability than their counterparts who received 1 mg per day of rasagiline early, according to a report published yesterday in the New England Journal of Medicine.
The study was funded by Teva Pharmaceutical Industries, the company that manufactures rasagiline.
If rasagiline only had an effect on symptoms, the level of disability between the early and late treatment group would have been the same, Olanow said. But since the early treatment group showed a significantly lower level of disability, then the rate of disease was modified and may have been inhibited.
"If it's slowing the disease, the deficit should persist, and that's what happened," said Olanow, who also consults for Teva.
Woods, who participated in the ADAGIO study, said he had an overall positive experience taking rasagiline and credits his continued good health to proper medication, exercise, and a positive attitude.
"I can't say it hasn't slowed me down at all," said Woods, noting his right hand is still stiff. "It hasn't gotten better, certainly, but it hasn't gotten significantly worse."
But the investigators cautioned that the results were somewhat ambiguous, as no disease-modifying effect was seen with a higher rasagiline dose of 2 mg per day.
Olanow suggested that 2 mg per day may have been so effective at reducing Parkinson's symptoms that the slowed disease progression was masked.
"It's an answer that is uncertain, however, it's tantalizing," said Dr. Karl Kieburtz, a professor of neurology and community and preventive medicine at the University of Rochester Medical Center, a consultant on the ADAGIO study and a medical expert for the Michael J. Fox Foundation for Parkinson's Research. "We don't know the mechanism for sure ... but does it have evidence of slowing the disease, and the answer, at least in [the 1 mg group] is yes."
But some experts were not inclined to accept the study's results.
Some Experts Don't Agree With ADAGIO Study
"I would be reluctant to accept the conclusion that this provides compelling evidence of slowed Parkinson's disease progression," said Dr. J. Eric Ahlskog, a neurologist at the Mayo Clinic in Rochester, Minn.
Dr. William Weiner, chairman of neurology at the University of Maryland and one of the trial investigators, said he disagreed with the NEJM report's emphasis on the possible disease-modifying effect.
"I would not have agreed to stressing the neuroprotection angle so strongly," he said. "[The outcome] may be statistically significant but it is surely not clinically meaningful."
But while medical data on the potential neuroprotective effects of some Parkinson's drugs is sparse, doctors have been aware that they may have such an effect for several years and prescribe them as such to patients.
Evan Henry, 54, from Newport Beach, Calif., said he was prescribed medications for symptom management and to slow disease progression when he was diagnosed with Parkinson's disease in 2003.
"It was both right from the get go," Henry said. "[I and my doctor] thought it was better to try it and see what happens than to squander an opportunity to help stave something off."
The study did not allow researchers to differentiate whether rasagiline was having a neuroprotective effect or whether it only treated symptoms while the brain compensated for any cognitive losses by dialing up the activity in other areas.
Laboratory studies on tissue cultures and animal models showed rasagiline can protect brain cells from dying, but Olanow noted that the drug may not have the same protective effect in Parkinson's patients.
Further research on other Parkinson's drugs to see if they might slow disease progression similar to rasagiline may help bolster the results of the ADAGIO study.
But any advance that hints at slowing the ravaging effects of Parkinson's disease can be appealing to patients.
"It's unfortunate that it's not black and white at the end of the study," said Henry, who did not participate in the ADAGIO trial and has never taken rasagiline. "The trajectory of Parkinson's advance for me is very slow ... But if something like rasagiline comes on the market and has scientific data behind it to show that it works, I'd be a fool not to try and take advantage of this kind of advance."
Despite skepticism, some neurologists said the ADAGIO results could be practice-changing.
"From this study alone and the use of this drug, the paradigm of Parkinson's treatment really should shift," said Dr. Daniel Kremens, a neurologist at Thomas Jefferson University in Philadelphia. "We should no longer be waiting; we should consider starting [patients] on treatment as soon as diagnosis is made, with hope that we can modify the disease course. And that's a major change in how Parkinson's is treated currently."