Promising new Parkinson's Disease drug

TriCities.com - Parkinson's patients are hoping a promising new drug will help them get the most out of their current medications. Those medications often bring complications to Parkinson's patients but a non-dopamine drug may be able to help smooth things out.

Terry Bogard's clarinet has been a hobby for years. He's determined that his parkinson's Disease won't rob him of his music.

Terry Bogard said, "gradually, as it's gotten worse, my left hand is less able to, particularly my little finger, operate the keys that they're supposed to."

That's pretty common for patients taking the standard treatment for Parkinson's, Levodopa.

Dr. Robert Hauser said, "the problem is with levodopa it's a medication that gets absorbed, peaks, and is cleared. So we're trying to take a target that we'd like to have nice and smooth and we're usually a bullet that goes up and down to shoot at that target."

When the fluctuations are mild, doctors can move the Levodopa closer together, or add other dopamine medication. but Doctor Hauser is studying a non-dopamine drug to help

Preladenant is in the category called A2A or adenosine 2A inhibitors. And what these medications do is they interact with the dopamine system in the brain but they're unique and different because they're not dopamine.

Terry, who spent his career in clinical research, was happy to travel to take part in Doctor Hauser's study.

Dr. Hauser said, "this drug interacts with that dopamine system past where dopamine does its thing and it tends to move the system back toward normal. So it does have a more prolonged effect uh but it works right now we think in concert with levodopa. So you still have the fluctuations from levodopa but overall it helps smooth out that clinical response."

The Phase 3 study of Preladenant is underway now at multiple sites (find them at http://clinicaltrials.gov/ct2/show/nct01155479).


Doctor Hauser says if all goes well with FDA approval, perhaps as soon as two to three years from now, it will be the first non-dopamine treatment for Parkinson’s Disease.

Promising Developments in Neurotrophic Gene Therapy for Parkinson’s Disease

Promising Developments in Neurotrophic Gene Therapy for Parkinson’s Disease
Raymond Bartus, Ph.D. and Joao Siffert, M.D.
NWPF.org - Ceregene, Inc., a biopharmaceutical company, is progressing with enrollment and dosing in its CERE-120 (AAV2-neurturin) Phase 2b multi-center, placebo (sham)-surgery, double-blinded controlled trial in Parkinson's disease.

The purpose of this Phase 2b study is to evaluate the safety and potential benefits of CERE-120 (AAV2-neurturin) in the treatment of Parkinson's disease. CERE-120 is an experimental biological drug that uses gene transfer technology to deliver human neurturin, a neurotrophic (growth) factor, directly into the brain areas most affected by Parkinson’s disease – the dopamine producing neurons. Similar to other growth factors (such as GDNF), neurturin has been shown in laboratory tests to restore function and protect brain cells from further damage.

CERE-120 has been carefully studied in laboratory animals without any toxicity, even following very high doses. In addition, in animals with neuronal degeneration and motor deficits similar to Parkinson's disease, CERE-120 was shown to protect brain cells and restore their function.

Three clinical studies were then successfully conducted in people with Parkinson’s disease, collectively providing evidence that CERE-120 can generally be delivered safely and may possibly reduce Parkinson’s symptoms (Marks et al., Lancet Neurol, 2008; Marks et al., Lancet Neurol 2010; Siffert et al. Neurology, 2011 (abstract))

This current trial has incorporated knowledge gained from the three previous trials and is intended to more clearly establish benefit of CERE-120, while further supporting its safety (Bartus et al., Mov Disord 2011). This study is actively enrolling participants in 11 centers across the United States. These sites are among the best movement disorders centers in the country and include Baylor College of Medicine (Houston, TX), Beth Israel Medical Center (New York, NY), Columbia University Medical Center (New York, NY), Duke University School of Medicine (Durham, NC), Emory University Hospital (Atlanta, GA), Mount Sinai Medical Center (New York, NY), Rush University Medical Center (Chicago, IL), Stanford University School of Medicine (Palo Alto, CA), University of Alabama (Birmingham, AL), University of California (San Francisco, CA) and University of Pennsylvania Hospital (Philadelphia, PA).

Study participants are randomly assigned (like the flip of a coin) to either receive CERE-120 or undergo a “placebo” (sham) surgery (where minimal surgical intervention occurs and no medication is injected). After the study procedure, participants are followed for approximately 18 months in a double blind fashion and up to 3 years for safety tests. To date, approximately 50% of the 52 subjects have enrolled and many others are in the process of being enrolled. It is anticipated that enrollment will be completed in the fall of 2011.

Once the Phase 2 study is completed (anticipated in early 2013), and if there is a benefit of CERE-120, participants who had a placebo surgery will be offered CERE-120 at no cost and prior to commercial availability of CERE-120.

For more information about the study, log on towww.ceregene.com or call toll free at 1-855-CERE120 (1-855-237-3120)                       

From NorthWest Parkinson Foundation:

Worms leading way in Mac Parkinson’s research thespec.com - McMaster University researchers are looking to an army of tiny worms to lead them to new treatments for Parkinson’s disease. In a highly unusual study, the Mac scientists will take advantage of the serendipitous fact that the tiny worms, called nematodes, and humans share genetic similarities in the brain’s dopamine neurons that are affected by people with Parkinson’s. The project will use researchers fromthe McMaster’s faculties of engineering, sciences and health sciences and is being financed with a $450,000 grant from the Collaborative Health Research Projects program of the National Science and Engineering Research Council and the Canadian Institutes of Health Research. Bhagwati Gupta, a professor in the department of biology, says nematodes are frequently used in medical research, especially in cancer studies, but only now has a way been developed to effectively use them in Parkinson’sdisease studies. Normally, the worms — barely visible to the human eye — are placed in a petri dish and their movements monitored when subjected to various stimuli.things. But Ravi Selvaganapathy, an associate engineering professor and expert in the design, fabrication and development of micro devices, came up with an ingenious micro channel device that restricts the movement of the worms. They can only wiggle forward or backwards, creating a more optimum circumstance for them to be observed and tested. “What we found was their neurological development can be tracked by the speed by which they respond to an electric field,” said Selvaganapathy. “We have a way of telling the worm something to do and it does something in response,” says Selvaganapathy. He says the electrical impulse works like a police officer telling a suspected drunken driver to walk a straight line. The officer decides on the neurological state of the person by the way he walks. In the same way, the movement of the tiny worms is observed to see if they are moving normally or abnormally. Irregularly moving nematodes, which have been modified, can be given various drugs and chemicals to see how they respond. Over the next few years, the McMaster researchers over the next few years will test the effects of more than 500 compounds on nematodes. The research can be done much more quickly and less expensively with the tiny worms than with laboratory rats. Ram Mishra, a professor in the department of psychiatry and neuroscience who studies nervous system degeneration, says the study procedure is very simple but it can answer complicated questions. He hopes that someday, the findings can be used to develop drugs to help humans with Parkinson’s.

29th June 2011 - New research

  MALE  FEMALE DIFFERENCES IN PARKINSON'S DISEASE

Maturitas [2011] Jun 24 [Epub ahead of print] (K.P.Roland, J.M.Jakobi, C.Powell G.R.Jones)

There are clearly more men than women with Parkinson's Disease. In some countries, the ratio of men to women with Parkinson's Disease is more than 2 to 3 times greater. Only in Russia, and to an even greater extent in Japan is Parkinson's Disease clearly more common in women. This may be due to the large number of men who died during warfare, rather than an actual greater prevalence. Men and women also differ in the prevalence of certain types of symptoms. Rigidity, postural instability, and also dyskinesia caused by L-dopa have all been found to be more prevalent in females with Parkinson's Disease. Reports suggest that females with Parkinson's Disease also have different walking patterns compared to males with Parkinson's Disease, and women who do not have Parkinson's Disease. Females with Parkinson's Disease also experience increased freezing when walking when compared to men. Balance is also reduced in females with Parkinson's Disease in comparison to men with Parkinson's Disease.

THE PREVALENCE OF DROOLING IN PARKINSON'S DISEASE

27th June 2011 - New research

THE PREVALENCE OF DROOLING IN PARKINSON'S DISEASE

Journal of Neurology [2011] Jun 23. [Epub ahead of print] (Kalf JG, Bloem BR, Munneke M.)

Drooling as symptom of Parkinson's Disease has so far been poorly defined. This uncertainty is reflected by high variations in published prevalence rates. Drooling is when saliva flows outside the mouth. Drooling is generally caused by excessive production of saliva, inability to retain saliva within the mouth, or problems with swallowing. The aim of this study was to investigate the prevalence of saliva loss and the accumulation of saliva in Parkinson's Disease as an initial stage, and diurnal (daytime) drooling versus nocturnal (nighttime) drooling.

Of those people with Parkinson's Disease, 29% had no complaints at all with saliva control, 43% of them experienced accumulation of saliva or only nocturnal (nighttime) drooling, and 28% had diurnal (daytime) drooling. Most of those that had daytime drooling had nighttime drooling as well. The longer somebody had Parkinson's Disease the more prone they were to nocturnal (nighttime) drooling. Drooling was independently associated with involuntary mouth opening, and swallowing complaints. Diurnal (daytime) drooling typically appeared as Parkinson's Disease got worse.

DRUGS CAUSING PARKINSON'S DISEASE

17th June
2011 - New research

DRUGS CAUSING PARKINSON'S DISEASE

Movement Disorders [2011] June 14 [Epub ahead of print] (Bondon-Guitton E, Perez-Lloret S, Bagheri H, Brefel C, Rascol O, Montastruc JL.) A study assessing over 20,000 adverse drug reactions has found those drugs that can cause or worsen Parkinson's Disease. This is normally described as drug induced Parkinsonism. Among the suspect drugs, most involved central dopaminergic antagonists (49%), followed by antidepressants (8%), calcium channel blockers (5%), peripheral dopaminergic antagonists (5%), and H1 antihistamines (5%). Cases with lithium, valproic acid, amiodarone, anticholinesterases, or trimetazidine were also found. Some problems occurred due to the interaction of other drugs.

The majority (60%) of people affected were female. Nearly half of all people affected were between 60 and 79 years of age. Seriousness was observed in 44% of cases. Nearly 70% of cases were observed during the first 3 months after introduction of the "suspect" drug (involving mainly central dopaminergic antagonists). A second peak (affecting 20% of cases) was found 12 months after drug introduction (mainly due to calcium channel blockers). The most frequently reported parkinsonian symptom was rigidity. Improvement was favourable after partial or complete withdrawal of suspect drugs in 88% of cases.

URINARY DYSFUNCTION IN PARKINSON'S DISEASE

23rd June
2011 - New research

URINARY DYSFUNCTION IN PARKINSON'S DISEASE

Neurology, Neurosurgery and Psychiatry [2011] June 13 [Epub ahead of print] (Uchiyama T, Sakakibara R, Yamamoto T, Ito T, Yamaguchi C, Awa Y, Yanagisawa M, Higuchi Y, Sato Y, Ichikawa T, Yamanishi T, Hattori T, Kuwabara S.)

Urinary dysfunction is common in Parkinson's Disease, but little was known about urinary dysfunction in early and untreated Parkinson's Disease. After excluding those with other conditions that might have influenced urinary function, patients were evaluated using a urinary questionnaire and urodynamic studies. Nearly two thirds (64%) of those people with Parkinson's Disease complained of urinary symptoms. More than a quarter (28%) had urinary difficulty. The main cause

of urinary difficulty is detrusor underactivity. The detrusor is the muscle that contracts when urinating to squeeze out urine. This is because Parkinson's Disease can affect all muscles, including even those used for urinating. Bladder outlet obstruction was present in 16% of people with Parkinson's Disease. Few patients experienced quality-of-life impairment owing to urinary dysfunction, despite the problems it can cause. The urinary symptoms and urodynamic findings were not correlated with gender, type of Parkinson's Disease, or disease severity, and so were not likely to worsen over time. In cases with severe difficulty in urinating, other diagnoses should be considered.

Potential Cause of Severe Sleep Disorder Discovered, Implications for Parkinson's Disease

Science Daily - Researchers at the University of Toronto are the first to identify a potential cause for a severe sleep disorder that has been closely linked to Parkinson's disease and other neurodegenerative diseases.

"Our research is the first to establish a potential genetic link to human REM sleep behaviour disorder (RBD). That's important because between 60 and 80 per cent of people diagnosed with human RBD develop Parkinson's disease or other neurodegenerative disorders later in life," says Dr. John Peever, lead author of the study that recently appeared in The Journal of Neuroscience.

Rapid-eye-movement sleep behaviour disorder (RBD) is most often characterized by violent movements that occur during dreaming sleep, also called rapid-eye-movement sleep. People who suffer from RBD do not experience normal muscle paralysis that prevents them from enacting their dreams and they often hurt themselves or their bed partners with their rapid, forceful movements. In some cases, patients need to be tied to their bed to prevent serious injury to themselves or their bedpartners.

Peever's team focused on investigating a genetic cause of RBD because the underlying cause of this disorder is unknown. There is evidence indicating that reduced brain inhibition could cause RBD, so Peever's team genetically reduced brain inhibition in mice and then recorded their sleep and muscle activity.

"We found that mice with reduced brain inhibition acted just like human RBD patients and they moved violently during REM sleep," says Peever. "This link strongly suggests that patients with RBD may also have impaired brain inhibition."

They also found that RBD symptoms in mice could be alleviated by giving them clonazepam -- a drug used to treat human RBD.

Peever's research underscores the importance of identifying a cause of RBD as 60 -- 80 per cent of RBD sufferers subsequently develop Parkinson's.

"Treating RBD could have direct implications for understanding and perhaps treating Parkinson's disease," says Peever.

Marching Through Life With Parkinson’s

JANE E. BRODY
The New York Times - Dr. Karen Jaffe, an obstetrician-gynecologist in Cleveland, was only 48 when she learned she had Parkinson’s disease. Four years later, she continues to maintain a full-time medical and surgical practice, even performing ritual circumcisions.

“I’m doing everything I can to stay healthy,” she told me in an interview. “My medications and exercises control my tremor, so doing surgery is not a problem.”

For patients with Parkinson’s disease, like Dr. Jaffe, there still is no cure. But researchers have begun to make progress in identifying causes of the disease, and a new study promises to help identify better treatments.

Until then, many patients are getting by on grit and determination. In speaking recently with several of them, two common threads emerged: an initial unwillingness to believe or reveal the diagnosis, followed by acceptance and a determination to pursue whatever it takes to remain as healthy and functional as possible.

In addition to taking medication designed to replace the brain chemical, dopamine, that is diminished in this neurological disease, each person I spoke with is dedicated to regular, often vigorous physical activity that can minimize the disabilities caused by Parkinson’s.

One, David Wolf, 51, of Buffalo, has even taken up fencing, saying (in jest, I hope), “There’s nothing like running someone through with a sword to make your day.” Another, Rena Bulkin, 68, of Manhattan, goes to a gym several times a week to do aerobics, stretching and range-of-motion and balance exercises. “If I don’t work out, my symptoms are much worse,” she said.

Dr. Jaffe dances the tango and whacks a heavy punching bag to reduce her symptoms and enhance function. “The punching bag helps my arms and relieves my frustrations,” she said. “It feels so good to hit the thing.”

She also rides an exercise bike at low resistance and high speed — 80 to 90 revolutions a minute — an activity that was shown in studies at the Cleveland Clinic to significantly reduce arm tremor.

The Parkinson’s patients also emphasized the importance of having a physician who is both expert in the disease and willing to work with patients to find treatments that produce the most benefits with the fewest side effects.

Theirs is a lesson worth learning by the growing numbers of people with Parkinson’s and their caregivers. The sooner one comes to terms with the diagnosis and starts treatment, the less rapidly the disease is likely to worsen.

More Than a Movement Disorder

Parkinson’s disease is a slowly progressive neurodegenerative condition involving a significant loss of dopamine, a neurotransmitter produced in a section of the brain called the substantia nigra that helps to control movement and emotional responses.

While manifestations of the disease can vary widely from person to person, the most common physical symptoms include tremor, or shakiness or trembling in the hands, arms, legs, jaw and face; rigidity of the muscles; slowness of movement or difficulty starting to move; and problems with balance and coordination.

Other symptoms may include fatigue, depression, anxiety, irritability, restlessness, tingling, memory problems, slowed thinking, changes in body temperature, sweating and constipation.

Although the disease usually does not produce recognizable symptoms until the seventh decade or beyond, it sometimes affects much younger people like Dr. Jaffe, Mr. Wolf and the actor Michael J. Fox, 50. Although Dr. Jaffe said she can no longer play the piano — “My left hand can’t keep up with my right hand, and I wasn’t very good in the first place” — she was able to knit a number of cotton wraps that were sold to raise money for the Michael J. Fox Foundation for Parkinson’s Research.

The foundation, in partnership with industry, is sponsoring an international study of biological markers that can help monitor progression of the disease. Results of the study, called the Parkinson’s Progression Markers Initiative, are expected to facilitate the testing of new drugs that may slow or stop the disease in its tracks.

Dr. Kenneth Marek, a neurologist at Yale University and principal investigator for the biomarkers study, said in an interview, “We need a way to keep track of whether a medicine is working or not.” Because the disease progresses very slowly in some patients and rapidly in others, different treatments are likely to be more effective in some patients than in others.

He said, “A roadblock in developing new drugs has been the inability to predict what will happen over time.”

Dr. Jaffe's husband is participating in this study, as a control subject. Two other participants, Marty Bullock, 68, of Stillwater, Okla., and his wife, Gay Lyn, plan to drive 560 miles every three months to Houston for the next five years, to be prodded and poked to give blood, urine and spinal fluid samples for analysis.

“After my diagnosis, I looked for a research program to participate in,” said Mr. Bullock. “It’s my understanding that Parkinson’s disease doesn’t get any better, so I wanted to see if perhaps I can help benefit someone else in the future.”

From Northwest Parkinson Foundation

Researchers identify why dopamine replacement therapy has a paradoxical effect on cognition

EurekAlert - Dopamine replacement therapy, which is used to manage motor symptoms associated with Parkinson's disease, can, at times, adversely affect cognition.

Dr. Oury Monchi, Ph. D. in neuronal modeling and Head of the Neurophysiological and Neuroimaging Research theme at the Centre de recherche de l'Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated with the Université de Montréal, and Dr. Penny A. MacDonald, Neurologist and postdoctoral fellow in Dr. Monchi's laboratory, have identified the reasons why within the framework of a clinical study recently published in Brain: A Journal of Neurology. This marks the second time in three months that Brain has published the results of IUGM researchers.

"The aim of our study was to understand the effects of dopamine replacement therapy on various aspects of cognition in patients with Parkinson's disease. When it comes to this particular disease, the part of the brain most affected by dopamine depletion is the striatum which is divided into several structures.

In Parkinson's disease, the dorsal striatum is more severely affected than the ventral striatum, which remains relatively unaffected, at least during the first phases of the disease. We observed that while dopamine replacement therapy enhances the functions of the dorsal striatum, it is at the expense of the ventral striatum which suffers a dopamine overdose, impairing its function", states Dr. Monchi.

Until now, the effect of dopamine replacement therapy on cognition in individuals with Parkinson's disease was controversial. The purpose of this study however, was to further investigate. This led to a series of laboratory tests and neuroimaging studies that allowed researchers to clearly define the distinct cognitive functions performed by the dorsal and ventral striatum, thereby shedding some light on the issue.

"The best treatment option for managing the motor symptoms of Parkinson's disease remains dopamine replacement therapy. In some patients however, it can have a negative effect on specific aspects of cognition.

Our discovery will therefore enable us to explore different medication and non-medication based avenues that could help improve the overall health of those affected. Our findings may contribute to helping develop personalized medicine - an avenue that is currently commanding a great deal of attention", exclaims Dr. MacDonald.