An Omaha scientist will start a human trial this summer involving the novel use of a drug that he hopes will halt the progress of Parkinson's disease.
The trial will include 16 patients with Parkinson's and 16 who don't have the progressive disease, which causes shaking, stiffness, trouble walking, balance problems and other difficulties.
The project is the first step in what Dr. Howard Gendelman envisions as a two-stage process to first halt the disease's progress and then, eventually, to defeat the protein-gone-bad that causes it.
“We hope to cure Parkinson's disease,” said Gendelman, chairman of pharmacology and experimental neuroscience at the University of Nebraska Medical Center. “I know it's a lofty goal.”
The disease is of particular interest to Nebraskans and Iowans because they are in the “Parkinson's belt”: Midwestern states that appear to have a high prevalence of the disease, perhaps because of agricultural pesticides or comparatively elderly populations, or for other reasons.
Today, patients can rely only on drugs and treatments that fight the symptoms but give way to the disease in the long run.
Scientists are “still looking for that magic drug,” said Michele Faulkner, an associate professor of pharmacy practice and medicine at Creighton University. “All of our drugs do nothing but treat the symptoms.”
Dan Lombardo of Omaha knows this. Diagnosed with Parkinson's in 2008, he has seen his shaking worsen and his walking grow more difficult. A foot drags sometimes. “I have to say 'Lift your toes up,'” the 58-year-old salesman said.
Lombardo is the only member of his large family — he had 12 siblings — with the disease. “So you start questioning what you did that gave you the Parkinson's,” Lombardo said. “You just don't have the answer.”
Nobody does. The disease is caused by the loss of nerve cells in the brain that produce dopamine, a chemical that controls movement and balance. Scientists don't know for sure what brings on the disease, nor do they know how to knock it out.
Gendelman's project will meld two kinds of technology: one a medication, the other a machine in the fight against Parkinson's. The scientist will use an immune-system stimulant sometimes used for patients receiving chemotherapy. Additionally, the project will scan the brains of participants using a fairly new noninvasive technology called magnetoencephalography, or MEG, to measure the brain waves of clinical trial participants.
Parkinson's has proved a formidable foe not only for patients but also for scientists seeking a cure. Human trials that have shown promise in mice inevitably have fallen short in people.
Numerous trials are taking place now in the United States and elsewhere, some to target the protein that is thought to trigger Parkinson's and others to treat symptoms, said Brian Fiske, vice president of research programs at the Michael J. Fox Foundation.
Fox, the 52-year-old actor, suffers from the disease and has become the leading spokesman in the fight against it.
The brain converts a medicine called levodopa into dopamine, Fiske said, and that treatment typically works well the first few years. But it wears off in time. It also produces side effects, such as involuntary movements.
Comparing Parkinson's case numbers from state to state is difficult. Nebraska is one of the few states with a registry to which doctors report their Parkinson's cases. A physician at Washington University in St. Louis, Dr. Allison Wright-Willis, has found that Midwestern and Northeastern states have fairly high incidences of the disease. She is assembling a state-by-state report involving Medicare beneficiaries with Parkinson's but would say through a spokesman only that Nebraska is in the top third of states.
The American Parkinson Disease Association said there may be anywhere from 500,000 to 1.5 million Americans with the disease. It's a tough disease to diagnose, association spokeswoman Kathryn Whitford said.
The MEG device at the Nebraska Medical Center has been used with epilepsy patients and patients with brain tumors and post-traumatic stress disorder, for pre-surgical planning and to study brain function in healthy individuals.
Tony Wilson, who oversees the med center's MEG device, said Gendelman approached him in 2010 about using the imaging device for Parkinson's.
The MEG will be used before, during and after patients receive the drug in Gendelman's trial. The U.S. Food and Drug Administration approved the trial last month.
The device enables scientists to pinpoint areas of brain injury by revealing where electrical circuits are broken. Through 306 sensors, the MEG detects and quantifies minute magnetic fields that naturally come from the electrical currents that are part of brain function. MEG provides a readout of that brain activity.
Nebraska Medical Center scientists have used MEG — a large device with an extension that fits on the subject's head like a helmet — to identify a signature pattern for Parkinson's.
“Now we're going to use that pattern to monitor change” in the clinical trial, Wilson said.
The med center acquired the device for about $2.5 million four years ago through a donation from an Omaha widow, now 86, who asked to remain anonymous. The device “is capable of doing so many things in the future,” the woman said Friday. “You can't outgive the Lord. He's always going to reward you one way or another.”
Gendelman has worked on Parkinson's research for more than a dozen years and was the subject of controversy in the late 1990s because he used fetal cells in some research. Gendelman said he switched to lab mice and hasn't used fetal cells in the lead-up to the human trial.
The clinical trial will start late this summer with daily injections of the 16 participants who have Parkinson's. Depending on results, the injections may go on for up to three months, followed by months of observation to monitor response. The 16 patients who don't have Parkinson's disease will be used for comparison purposes in the MEG studies.
Gendelman believes the immune system reacts too vigorously to the inflammation and damage caused by Parkinson's disease.
Malú Tansey, an Emory University physiologist with training in neurodegeneration, said the immune system not only fights the inflammation but also appears to kill off still-living but wounded nerve cells. These nerve cells are still functional, she said, so the immune system's reaction hastens the disease's progress.
Thus, Tansey said, it makes sense to attempt to harness that immune system, somewhat like a switch that can dim or brighten a light. Tansey is familiar with Gendelman's work but isn't involved in it.
Gendelman will use a drug, called Leukine, to temper the immune system in hopes of preventing it from attacking the injured nerve cells. The strategy has shown good results in mice.
If the trial works well, Gendelman expects to deploy a vaccine he is developing. The vaccine, which appears to work well in mice, theoretically would fight the protein that causes the disease. That would be phase two of Gendelman's mission.
He said he's not alone at the med center on the Parkinson's project. “To go from a mouse to a human (trial) takes a village, takes a team,” he said.
Dan Lombardo hopes someone finds a new strategy or drug to fight the disease. Meanwhile, he takes three medications and lifts weights, keeps his core strong and takes an aerobic kick-boxing class. He has tried meditation and acupuncture.
Scientists are bound to figure it out, he reasons. It will happen, he said, in the next five years.
“I said that five years ago, too.”
Still, Lombardo strives to stay positive and not look too far ahead. “Some days I just feel great and some days I feel like I've got Parkinson's.”