Progress against Parkinson's disease

UC Irvine Health doctors aim for earlier diagnosis and treatment of a mysterious ailment

June 26, 2016
Parkinson's disease

Every evening after dinner, just as the sun is waning in the western sky, Arthur “Jay” Sagen begins to feel troubled and turns to his wife of 51 years, Diane, for reassurance. Jay, 76, was diagnosed with Parkinson’s disease—a degenerative brain disease—six years ago.

He has the typical symptoms of tremors and difficulty moving. And like many patients in the advanced stages of the disease, he occasionally experiences delusional thinking or hallucinations.

The behavioral symptoms surfaced a few years ago when the retired artist and art teacher started seeing black cats squirt by in the periphery of his vision. Then one day in 2013, Diane, 72, a retired marriage and family therapist, came home and Jay warned her, “The living room is full of people.”

“It was upsetting, but I had read that there was a possibility of hallucinations,” Diane says. “His symptoms are usually worse at night when the light is dimmer and he can misread things. Usually after dinner we have quite a conversation about who is and who isn’t here.”

For treatment and support the Sagens turn to the UC Irvine Health Parkinson’s Disease and Movement Disorders Program, where experts recognize the broad array of symptoms and are equipped to help. The overarching goal of the program is to keep patients functioning as well—and for as long—as possible while searching for a cure to this mysterious condition.

“They are so knowledgeable,” Diane says of the program’s staff, composed of four physicians, including her husband’s physician, Dr. Neal Hermanowicz, director of the Movement Disorders Program.

 Parkinson's disease progression

About 1 million Americans are afflicted with Parkinson’s disease and related “Parkinsonian” movement disorders, such as Lewy body dementia. The risk of developing the disease increases with age, and the average age of diagnosis is 60. Thus, with an aging population, about 2 million Americans will be living with the disease by 2030, Hermanowicz says.

Parkinson’s disease attacks a part of the brain called the substantia nigra and causes the destruction of cells that produce dopamine, a neurotransmitter critical to movement and cognitive function. As dopamine is lost, classic Parkinson’s disease symptoms set in, including tremor, rigidity, weakness, problems with posture, and behavioral symptoms such as confusion, anxiety and hallucinations.

Aiming for earlier diagnosis and treatment

It’s not yet clear, however, what causes the disease or even where it begins. According to research presented at a fall 2015 symposium on the disease at UC Irvine, the disorder may begin outside the brain—perhaps in the peripheral nervous system. Pinpointing where the disease originates and identifying its earliest biological signals, called biomarkers, could lead to earlier diagnosis and more effective therapies to preserve brain function, says Dr. Howard Federoff, dean of the School of Medicine and vice chancellor of UC Irvine Health. Federoff is also one of the nation’s foremost experts in Parkinson’s research.

“Twenty-five years ago we knew far less than we know today about Parkinson’s,” he says. “It is our conviction that the earlier the diagnosis, the better the chance to do neuro-protection.”

Researchers already know that some of the earliest symptoms of the disease include a deteriorating sense of smell as well as constipation, rapid eye movement, anemia, anxiety, mood problems and sleep disturbance.

“For the last 10 or 15 years, the emphasis has been not just on motor symptoms; it has changed to detecting much earlier symptoms, such as mood changes, sleep changes, bowel movement problems,” says Dr. Nicolas M. Phielipp, an assistant professor in the Department of Neurology. “These seem to be symptoms that herald the motor aspects of the disease.” Phielipp is also part of the Movement Disorders Program along with Dr. Anna Morenkova; both fellowship-trained in movement disorders. The fourth member of the team is Dr. Frank Hsu, chair of the Department of Neurosurgery and an expert in surgical treatment.

In the past decade or two, many treatments for Parkinson’s disease and other Parkinsonian movement disorders have been tried and failed. But experts now suggest that perhaps those therapies might work in patients who are diagnosed earlier—with less-advanced disease—rather than on patients who are in more advanced stages, Phielipp explains.

UC Irvine Health is at the forefront of research in earlier diagnosis and treatment. Phielipp is launching a project seeking to identify early, specific biomarkers of the disease by examining the brain with sophisticated imaging devices and muscle recordings while individuals perform simple motor tasks, like tapping their fingers on a table.

“If we can find an early marker of the condition, even without fully understanding what is going on, trying therapies earlier in the disease process increases our chances of success in trying to slow down or stop the disease,” he says.

UC Irvine Health is also part of the prestigious Parkinson Study Group, a nonprofit organization of physicians and other healthcare providers from medical centers in the United States, Canada and Puerto Rico experienced in the care of Parkinson’s patients and dedicated to clinical research. The group is enrolling participants in several studies, including a Phase 3 study, called STEADY-PD, to assess a medication called isradipine and its ability to alter the progression of Parkinson’s disease.

“We have a very large clinical trials program at UC Irvine Health neurology,” says Dr. Steven L. Small, professor and chair of the Department of Neurology. “UC Irvine Health neurology is focusing not only on the state-of-the-art treatments of all neurological diseases but also on experimental agents that we think can help when other things can’t help. We have many clinical trial options.”

Gene therapy holds promise

Other studies are underway to assess drugs that impact motor symptoms. And Federoff is part of a multicenter study group exploring gene therapy for Parkinson’s disease. The first gene therapy clinical trial for Parkinson’s disease began in 2003, and one decade later five such trials were underway. The progress reflects an improved understanding of the brain biology and anatomy, Federoff says.

Gene therapy involves introducing a healthy, functioning gene into the brain that will begin making a fresh supply of dopamine. Federoff and his colleagues have devoted many years developing a tool, called a viral vector, for safely delivering gene therapy to the brain. They disable a virus, removing its infectious material, and transfer an engineered gene into the cell.

“The vector is a way to deliver the payload,” he explains. “It’s engineered to carry the therapeutic gene. The aim is to support the health of the neuron so it can function properly.”

The researchers have already shown that the viral vector is safe and well-tolerated by patients, and they’ve learned how to make the vector in large quantities—another crucial step. The next phase of the research focuses on using the vector to deliver a gene with information capable of producing a substance called glial cell-derived neurotrophic factor (GDNF). GDNF is a chemical that may help protect and strengthen brain cells that produce dopamine. Studies in non-human primates show that delivering the GDNF gene to the brain causes brain cells important to dopamine production to stabilize and even regrow.

A Phase 1 clinical trial to test the therapy’s safety and tolerability in 24 patients is now underway at the National Institutes of Health. “We will have more data than has ever been collected, and I think this will greatly inform us going forward,” Federoff says.

Preserving quality of life

While future treatments may arrest or cure the disease, UC Irvine Health professionals today offer a broad array of treatments and support services to help patients remain as functional as possible. The remarkable drug levodopa is a mainstay of Parkinson’s disease therapy. The drug treats the symptoms of stiffness, tremors and muscle spasms.

Some patients are also candidates for deep-brain stimulation, a surgery for Parkinson’s disease. Deep-brain stimulation involves surgically implanting a battery-operated device in the brain, similar to a heart pacemaker, that delivers electrical pulses to areas of the brain that control movement and blocking abnormal nerve signals that cause tremors, rigidity and movement problems. It is considered for people whose symptoms respond to levodopa but experience bothersome motor fluctuations, Phielipp says.

“We have a very active, clinical deep-brain stimulation program at UC Irvine Health,” he explains. “We do offer this treatment when it’s appropriate. It’s not for everyone. Patient selection is very important to its success.”

Another significant focus of the UC Irvine Health program is on the behavioral symptoms of Parkinson’s disease. While often unaddressed, symptoms like delirium, hallucinations, anxiety, depression, apathy and compulsive behavior are not uncommon. Doctors can prescribe antipsychotic medications to help alleviate behavioral symptoms.

Families are also educated about what to expect and are steered to resources for support. For a time, Diane and Jay Sagen attended an exercise group for patients with Parkinson’s disease and their caregivers. Jay is now on a medication to quell the hallucinations, while Diane attends a caregiver support group and does yoga to alleviate stress.

Jay sometimes doesn’t recognize Diane and demands to know where his wife is. Occasionally she picks up her home phone and calls herself on her cell phone so that Jay can “speak to her.”

“I get impatient at times because I know certain things are not true, and I want him to know it’s not true,” she says. “He takes a low dose of a medication called clozapine now, and it has helped. And I can get Dr. Hermanowicz on the phone when I need him.”

About 50 percent of people with Parkinson’s have symptoms of hallucinations, often mild, says Hermanowicz. The hallucinations are most commonly visual but also can be auditory, such as hearing people speak in the home when no one is present, or they may be tactile, such as the sensation of someone touching them. Delusions are less common but can include thinking that someone is going to harm them or is stealing their money, he says.

“Delusions are always unpleasant, nasty and disruptive,” he says. “I’ve had patients call 911 at 3 a.m. because they thought someone was trying to break into their house.”

A meticulous evaluation of the patient can help pinpoint what may be causing the symptoms. Antipsychotic medications are often prescribed, Hermanowicz says. The healthcare team also works hard to address depression and anxiety that may accompany the disease.

“Parkinson’s keeps people in their chairs,” he says. “Exercise can play an important role in treating depression.” Hermanowicz often refers patients to a therapist at UC Irvine Health who is specially trained in Parkinson’s disease.

He and his colleagues also steer patients and their caregivers to support services. Hermanowicz co-founded the California Parkinson’s Group to foster support and collaboration among individuals and families in Orange County living with young-onset Parkinson’s disease.

“Quality of life concerns drive our actions,” Phielipp says. “If we don’t yet have the cure, the main goal of every visit is addressing quality of life.”

UC Irvine Health is especially equipped to address the broad array of needs, Small says. The UC Irvine Health Department of Neurology has doubled in size in just last five years.

“As an academic medical center, all our specialists are subspecialty trained,” he says. “Everyone who takes care of Parkinson’s disease in our institution has a Parkinson’s disease fellowship. UC Irvine Health neurology is an huge resource for world-class care in Orange County.”

Learn more about Parkinson's disease at ucirvinehealth.org/parkinsons.

— UC Irvine Health Marketing & Communications
Featured in UC Irvine Health Live Well Magazine Winter 2016

 

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