New device may reduce swallowing health risk in patients with Parkinson's disease

Speech pathologist Christine Sapienza (right) helps patient Lou DeLaney use an Expiratory Muscle Strength Training device at the UF Speech and Hearing Center on Sept. 29, 2010. New UF research shows that EMST therapy can improve swallowing function in patients with Parkinson’s disease.

28 nov 2010-- A hand-held device that strengthens the muscles involved in swallowing can address a serious symptom of Parkinson's disease, according to a new University of Florida study.

In what researchers believe is the largest randomized trial of a behavioral swallowing treatment in patients with Parkinson’s disease, scientists found that about one-third of the volunteers who used the device improved their ability to swallow. The findings appear in the Nov. 23 issue of the journal Neurology, the medical journal of the American Academy of Neurology.

Nearly 1 million Americans have Parkinson’s disease, according to the Parkinson’s Disease Foundation. Finding solutions to their swallowing problems is important because their most common cause of death is pneumonia caused by inhaling foreign material, such as food, during swallowing.

“The many muscles involved in swallowing progressively weaken in patients with Parkinson’s disease and become uncoordinated in the same way that patients lose coordination and strength in their arms and legs,” said Michelle Troche, the study’s lead investigator and a clinical lecturer and speech pathologist in the UF College of Public Health and Health Professions’ department of speech, language and hearing sciences.

It also becomes more difficult for patients to sense material in their airways and cough hard enough to expel it, she said.

For the study, researchers trained participants with Parkinson’s disease to exhale into an Expiratory Muscle Strength Training, or EMST, device. In previous studies, EMST has improved swallowing and cough function in patients with multiple sclerosis and in elderly, sedentary adults.

“EMST uses the basic exercise theory behind any strength training program,” said co-investigator Christine Sapienza, a professor and chairwoman of the department of speech, language and hearing sciences. “This small device capitalizes on that concept of overload with a calibrated pressure release valve that won’t open until you generate a great enough lung pressure. The patient or clinician can vary how much pressure is needed to open the valve on the device. The greater the pressure you need, the stronger the muscles have to be. It acts much like a pin on a weight machine and uses the same concept to strengthen the muscles involved in swallowing and breathing.”

Sapienza developed the device along with UF researchers Paul Davenport, a professor and interim chairman of the department of physiological sciences in the College of Veterinary Medicine, and A. Daniel Martin, a professor in the department of physical therapy.

“Their efforts are pioneering and it is likely that this study will stand the test of time as a landmark in Parkinson’s disease swallowing research,” said research collaborator Dr. Michael Okun, a co-director of UF’s Movement Disorders Center and an associate professor of neurology with the College of Medicine and UF’s McKnight Brain Institute.

Participants in the Parkinson’s disease study were divided into two groups of 30. In one group participants used the EMST device with proper calibration. The other participants used a device that looked exactly the same but did not work to strengthen the muscles. Neither the participants nor the study therapists knew who had the real device and who had the sham device. Participants used the devices in their homes for 20 minutes a day, five days a week for four weeks. Therapists visited once a week to make sure participants used the device correctly. Following the study period, participants in the sham group received the EMST treatment.

The researchers measured participants’ swallowing function before and after treatment with a standardized swallow safety scale, the Penetration-Aspiration scale, developed in part by UF faculty member John Rosenbek, also with the department of speech, language and hearing sciences. Researchers used videofluoroscopy to obtain motion X-ray images of the participants’ swallowing muscles as they swallowed liquid.

One-third of participants who used the device with calibration had significantly improved swallow safety scores compared to 14 percent of the participants in the sham group. The researchers also found that for patients in the treatment group, there was greater movement in the muscles that lift the voice box out of the way during swallowing. Quality-of-life measures related to swallowing improved in both the treatment and sham groups.

“The fact that EMST is a home-based treatment is of particular importance as many individuals with Parkinson’s disease cannot travel the long distance to attend clinic or hospital therapy sessions,” said Stephanie Daniels, a visiting associate professor at the University of Houston and an assistant professor at Baylor College of Medicine, who was not involved in the study. “Very few swallowing treatment studies have incorporated the rigorous research design used in this study. We need more studies such as this to support the different treatment approaches used in swallowing rehabilitation.”

Sapienza has a potential financial interest in Aspire Products LLC, the manufacturer of EMST. Portions of the study were funded by the Veterans Affairs Rehabilitation Research and Development, the Michael J. Fox Foundation and the National Institutes of Health. The UF Movement Disorders Center receives support from the National Parkinson Foundation Center of Excellence.

Provided by University of Florida

Immune system gene linked with Parkinson's: study

CHICAGO, 17 aug 2010– A gene linked with the immune system may play a role in developing Parkinson's disease, researchers said on Sunday, marking a possible advance in the search for effective treatments.

They said a gene in the human leukocyte antigen region or HLA -- which contains a large number of genes related to immune system function -- was strongly linked with Parkinson's disease.

"That means the immune system probably plays a role in your body developing Parkinson's disease," said Dr. Cyrus Zabetian of the University of Washington and Veteran's Administration Puget Sound Health Care System, whose study appears in the journal Nature Genetics.

Zabetian said there had been hints that the immune system may be linked to Parkinson's disease, a neurodegenerative disease that affects 1 to 2 percent of people over age 65.

"This is the best evidence we've seen so far," Zabetian said in a telephone interview.

The finding came from a large, long-term study of more than 2,000 Parkinson's disease patients and 2,000 healthy volunteers from clinics in Oregon, Washington, New York and Georgia.

Parkinson's sufferers have tremors, sluggish movement, muscle stiffness and difficulty with balance.

Researchers looked at clinical, genetic and environmental factors that might contribute to the development and progression of Parkinson's disease and its complications.

"We found strong evidence that a gene within the HLA region is associated with Parkinson's disease," Zabetian said.

HLA genes play an important role in helping the body discern between foreign invaders and the body's own tissues.

"We don't know specifically which gene because there is a cluster of genes in that region, but it is the first really strong link that the immune system plays a role," he said.

That may mean infections, inflammation or an auto-immune response play some role in the development of Parkinson's disease, Zabetian said.

"What this allows us to do is to hone in on the immune system," he said.

Although current medical treatments may improve symptoms, none can slow or halt the progression of the disease.

The study was funded in part by the National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health.

Study Finds Features Linked to Mortality Risk in Parkinson's


Cognitive impairment, dysphagia, postural instability gait difficulty associated with risk

16 nov 2009-- A variety of motor and non-motor factors may be associated with a higher risk of mortality in patients with early Parkinson's disease, according to research published in the November issue of the Archives of Neurology.

Raymond Y. Lo, M.D., of the Parkinson's Institute and Clinical Center in Sunnyvale, Calif., and colleagues analyzed Kaiser Permanente Medical Care Program data on 573 subjects with Parkinson's disease that was newly diagnosed during 1994 and 1995. Subjects were followed for death until the end of 2005.

During follow-up, the researchers note that 352 subjects died. Factors associated with a higher risk of all-cause mortality included severe cognitive impairment based on Mini-Mental State Examination scores, symmetry of motor signs, older age at diagnosis, dysphagia, and postural instability gait difficulty subtype (hazard ratios, 2.7, 2.0, 1.1, 1.4, and 1.8, respectively).

"In this multiethnic incident Parkinson's disease cohort, we conclude that several motor and non-motor features in early Parkinson's disease can predict higher mortality risk, particularly older age at diagnosis, postural instability gait difficulty, cognitive impairment, and hallucinations. Our findings are in keeping with those of others, suggesting that these results are robust and generalizable. With effective clinical predictors, we can improve understanding of the disease process, refine risk stratification in designing clinical trials, and guide decision making in clinical practice," the authors conclude.

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Attempting to zap Parkinson's through spinal cord

WASHINGTON, 20 mar 2009 – Implanting a pacemaker-like device deep in the brain helps some Parkinson's disease patients move better, but could less risky zapping of the spinal cord work instead? It did in mice and rats nearly immobilized with Parkinson's-like symptoms: Scientists at Duke University Medical Center turned on the electricity and videotaped the rodents immediately scurrying around almost like normal.

The research, reported in Friday's edition of the journal Science, is just a first step. More animal testing is needed to tell if the approach could be tried in people. Implants in marmosets, a type of primate, are to begin soon.

But sufferers of chronic pain already can have spinal cord stimulators implanted that send electrical currents to block the "I'm hurting" messages sent to and from the brain. For Parkinson's, the idea is similar.

The 1.5 million Americans with Parkinson's gradually lose brain cells that produce dopamine, a chemical key to the circuitry that controls muscle movement. The result: Haywire brain signaling that leads to increasingly severe tremors and periodically stiff or frozen limbs. Medication helps early in the disease. More severely affected patients may try "deep brain stimulation," where wires are implanted inside the brain to deliver tiny electrical zaps that disable overactive nerve cells and improve motor control.

Exploring a less invasive approach, the Duke team attached tiny wires to the spinal cords of mice and rats whose brains produced so little dopamine that they had the slow, stiff motions of advanced Parkinson's disease.

When the electricity was turned on, the animals became 26 times more active and movement visibly improved in seconds, Duke neuroscientist Dr. Miguel Nicolelis and colleagues wrote.

Why would it work?

Proper movement requires orderly nerve cell firing to different muscles at different moments in time, like members of an orchestra must play in proper sequence for a symphony.

There's increasing if circumstantial evidence that rhythmic waves of brain activity, called oscillations, play a role in Parkinson's movement problems — and that interrupting those abnormal waves allows the more normal, symphony-like brain cell firing to resume, said Dr. Walter Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke, which helped fund the work.

The spinal cord stimulation appears to have sent a signal up to the brain that interrupted those oscillations.

Koroshetz cautioned that much work remains, including testing whether the stimulator's effect might last long enough to be useful.

But, "it's something that has definitely got some scientific traction to it," he said. "It's a really good idea."

Clues on how trace metal may be linked to Parkinsons: study

PARIS 02 feb 2009 – Manganese, a metal that is naturally present in the human body, may contribute to Parkinson's disease when defective genes interact to enhance its toxicity, according to a study published Sunday.

Parkinson's attacks the nervous system and is characterized by the loss of cells which produce dopamine, a critically important neurotransmitter that ferries chemical messages within the brain.

Symptoms include muscular rigidity, difficulty with initiating movements, lack of balance, and slowness of voluntary actions.

In experiments on yeast cells, researchers showed that the toxicity caused by an over-abundance of a protein, alpha-synuclein, previously linked to the disease is greatly reduced in the presence of a second protein, known as ATP13A2.

The latter is thought to play a role in transporting metal molecules, especially manganese, a known risk factor for Parkinson's.

Manganese is an essential trace nutrient in virtually all forms of life. The human body contains about 10 milligrammes, stored mainly in the liver and kidneys.

A team led by Susan Lindquist at the Howard Hughes Medical Institute in Cambridge, Massachusetts demonstrated that yeast cells lacking ATP13A2 were more sensitive to the metal.

They were able to duplicate the same genetic interaction in laboratory-grown rat neurons.

Their findings, published in Nature Genetics, a publication of the Nature Publishing Group, suggest that humans with mutations in the genes encoding these proteins may be particularly vulnerable to manganese poisoning.

A neurodegenerative condition similar to Parkinson's -- often called "manganism" -- has been linked to manganese exposure amongst miners and welders.

Manganese exposure is regulated by the US Occupational Safety and Health Administration.

Meanwhile, in another study published in Nature Genetics, researchers identified the first genetic variant ever linked to the condition known as essential tremor.

Like Parkinson's, essential tremor is a degenerative neurological disease characterised by tremor of the arms and hands that can impair writing, drinking, eating and other everyday activities.

Earlier studies suggested that the condition may occur in as many as 13 percent of persons over 65.

Researchers led by Kari Stefansson of deCODE Genetics, a company based in Reykjavik, Iceland, compared the genomes of 452 essential tremor patients from Iceland against a control group of 14,394 persons.

They found that a specific variant in the gene known as LINGO1 was strongly linked to the disease.

LINGO1 is involved in cell-to-cell interactions within the nervous system, and is known to regulate neuron survival.

Inhibiting the gene's activity has been shown to improve neurological function in test animals, and could be a promising path for new drug treatments.

Pioneering gene therapy for Parkinson's shows early progress

The first attempt at gene therapy against Parkinson's disease has yielded promising results and is safe, according to early data from this ground-breaking experiment.
The pilot study, conducted among 11 men and one woman in New York, marks the first-ever use of a "Trojan horse" technique against this tragic disease.
It entails taking a gene and tucking it inside a disabled cold virus, which is then injected into a key area of the brain. The harmless virus "infects" the local cells and thus stealthily delivers the corrective piece of genetic code.
The 12 volunteers, all of whom have advanced Parkinson's, showed significant improvement in trembling, jerkiness and other symptoms, and none had any side effects, according to an assessment carried out a year after the operation.
The paper, appearing Saturday in the British journal The Lancet, could be an important spur for gene therapy.
In the 1990s, the dramatic rise of biotechnology spurred hopes of a "new dawn" for medicine in which inherited diseases could be wiped out by simply replacing the faulty genes in targeted cells with the right ones.
But this vision became darkened by setbacks as scientists gradually realised that an individual's genome is complex, interwoven tapestry -- and substituting one gene with another can have far-reaching consequences elsewhere.
In 1999, this frontier research was blighted by the death of an 18-year-old American volunteer, Jesse Gelsinger, whose immune system ran amok following a gene transplant to fix a liver enzyme deficiency.
In 2002, French researchers were stunned when three out of 10 children they had cured with corrective genes to fix X-SCID, an inherited immunodeficiency disorder, suddenly developed leukaemia.
In this climate of deep prudence, researchers led by Matthew During, a professor at Cornell University's Weill Medical College, Cornell University, were placed under tight constraints in their experiment, which aimed primarily at testing for safety.
Parkinson's is an incurable, degenerative disease of the central nervous system that causes uncontrollable shaking, along with impaired speech and movement. In approximately one third of cases it also results in dementia. The disease affects at least one percent of people over the age of 65.
The cause is a loss of dopamine, a chemical messenger that helps direct movement. The substance is provided in a part of the brain called the substantia nigra.
Attempts to treat Parkinson's have focussed essentially on providing a pharmaceutical substitute for dopamine or on restoring or protecting dopamine-producing cells.
During's team took a different tack, though. They aimed at part of the brain called the subthalamic nucleus, which becomes hyperactive as a result of Parkinson's and "blocks" signals to the nervous system, thus hampering motor control.
Using a magnetic resonance imaging (MRI) scanner to pinpoint their operations, the team delicately delivered a gene that controls an enzyme, glutamic acid decarboxylase (GAD), into the volunteers' subthalamic nucleus.
The idea was to use the gene as a switch to reverse the subthalamic nucleus' activity, turning it into an inhibitor rather than exciter of motor output signals.
None of the patients suffered any ill-effects from the surgery, or from the transplanted gene. Within three months of the operation, they reported substantial improvements in the side of the body that was opposite to the brain hemisphere where the gene was delivered, and the improvement continued until 12 months, the endpoint of the trial.
The researchers say the results, while preliminary, are encouraging, especially as US health watchdogs only gave them cautious authorisation for a gene transplant on one side of the brain, not both.
But Parkinson's researcher Jon Stoessl of the University of British Columbia, expressed caution.
The long-term effect of this therapy on the subthalamic nucleus' role in learning remains unclear, he said in a commentary, also carried by The Lancet.
Another unknown is whether the virus, even though disabled and transferred to only a tiny part of the brain, could affect neighbouring structures, he said.
Finally, there was no proof yet that this technique was any more effective than tried-and-tested implants to stimulate the subthalamic nucleus, Stoessl said.

FDA OKs drug patch to treat Parkinson's

The treatment options for patients with early Parkinson's expanded Wednesday with the approval of a new drug in patch form — a first for medicines to treat symptoms of the disease.
The once-daily Neupro patch contains a drug called rotigotine, which has not been sold before in the United States, the Food and Drug Administration said. The drug patch, made by Schwarz Pharma AG, is the first for the treatment of symptoms of Parkinson's disease.
Parkinson's disease results from the loss of dopamine-producing brain cells. Dopamine is crucial for the communication between cells that control muscle movement, which explains the trembling commonly seen in Parkinson's patients.
Rotigotine works by activating dopamine receptors in the brain, mimicking the neurotransmitter's effect.
The most common side effects for Neupro include skin reactions at the patch site, dizziness, nausea, vomiting, drowsiness and insomnia, the FDA said. Most are typical with this class of drugs.
Other potential safety concerns include sudden onset of sleep while engaged in activities such as driving or operating machinery, hallucinations and decreased blood pressure when standing up, the agency said.
An estimated 1 million people in the U.S. have Parkinson's, with an additional 60,000 cases diagnosed each year.

Ropinirole Prolonged-Release Reduces Parkinson's 'Off' Time

KANSAS CITY, Kan., April 2 -- For patients with Parkinson's disease poorly controlled by levodopa alone, the addition of ropinirole (Requip) both reduced "off" time and allowed for lower doses of levodopa, found a multicenter international study.
Among 393 patients in the randomized study, prolonged-release ropinirole as an adjunct to levodopa led to a mean reduction in daily "off" time of 2.1 hours, compared with 0.3 hours for patients on placebo, reported Rajesh Pahwa, M.D., of University of Kansas here, and colleagues, in the April 3 issue of Neurology.
"We also found the drug helped improve quality of life and motor function," said Dr. Pahwa and colleagues.
Ropinirole is a non-ergot dopamine agonist used as both monotherapy and adjunctively for early and advanced Parkinson's disease. The drug is also approved for restless legs syndrome.