November 13, 2009 by mike.

Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson’s disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson’s disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.

“Statins are one of the most widely used cholesterol-lowering drugs throughout the world,” said study author Kalipada Pahan, PhD, professor of neurological sciences at Rush University Medical Center. “This may be a safer approach to halt the disease progression in Parkinson’s patients.”

Pahan and colleagues from Rush, along with researchers at the University of Nebraska Medical Center in Omaha published these findings in the October 28 issue of the Journal of Neurosciences.

The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson’s pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson’s.

“Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson’s,” said Pahan. “If we are able to replicate these results in Parkinson’s patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease.”

The study was supported by grants from National Institutes of Health and Michael J. Fox Foundation for Parkinson’s Research.

Parkinson’s is a slowly progressive disease that affects a small area of cells within the mid-brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in dopamine, which is a vital chemical neurotransmitter. The decrease in dopamine results in one or more of the classic signs of Parkinson’s disease that includes, resting tremor on one side of the body, generalized slowness of movement, stiffness of limbs, and gait or balance problems. The cause of Parkinson’s disease is unknown. Both environmental and genetic causes of the disease have been postulated.

Parkinson’s disease affects about 1.2 million patients in the United States and Canada. Although 15 percent of patients are diagnosed before age 50, it is generally considered a disease that targets older adults, affecting one of every 100 persons over the age of 60. This disease appears to be slightly more common in men than women.

Source: Deborah Song
Rush University Medical Center

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November 13, 2009 by mike.

Researchers at Iowa State University have found an essential key to possibly cure Parkinson’s disease and are looking for others.

Anumantha Kanthasamy, a distinguished professor of biomedical sciences and W. Eugene and Linda R. Lloyd Endowed Chair in Neurotoxicology at the ISU College of Veterinary Medicine, has been working to understand the complex mechanisms of the disease for more than a decade and thinks he has found hope for the cure.

Parkinson’s disease sufferers lack a sufficient amount of a brain chemical called dopamine.

Kanthasamy’s research shows that there is specific protein that is naturally present in human brains that — for no known reason — kills the brain cells that make dopamine.

The cells that are being killed are the ones that produce the needed dopamine.

“We have millions of cells in our brains,” said Kanthasamy, “In Parkinson’s, about 10,000 of these brain cells die; no one knows why.”

Kanthasamy discovered that a novel protein — known as protein kinase-C (specifically PKCδ) - is killing the dopamine-producing cells.

Kanthasamy and his research staff discovered a compound that neutralizes the cell-killing kinase-C and allows the dopamine-producing cells to survive and function.

“With a lot of hard work, and little bit of luck, we found something important,” he said. “And when you find something like this you say, ‘This is great because it can be a target for developing new drugs.’”

Now, Kanthasamy’s group is looking for additional compounds that also can serve to neutralize protein kinase-C. By identifying more compounds that perform the function of neutralizing kinase-C, researchers are more likely to locate one that works well and has few side effects.

This discovery is expected to provide new treatment options to stop the progression of the disease or even cure it.

The study is being funded by a Grow Iowa Values Fund grant. The goal of the grant program is to support development of technologies with commercial potential and to support the growth of companies using those technologies. Kanthasamy is working on this research with PK Biosciences Corp., an Iowa-based startup company. Funding was also provided by the National Institutes of Health.

“Once we find the compound, we need to make sure it’s safe. If everything goes well, it could take about 10 years, and then we might be able to see something that will truly make a difference in the lives of people with this disorder,” said Kanthasamy.

Parkinson’s disease strikes around 50,000 people each year, and there are approximately 1 million people with the disease. Parkinson’s sufferers include actor Michael J. Fox and former boxing champion Muhammad Ali.

As people grow older, the cells that produce dopamine naturally die, causing dopamine levels to fall gradually over time. When the levels continue to drop below 60 to 70 percent, the person will start to have Parkinson’s disease symptoms, according to Kanthasamy.

“Everybody has a little Parkinson’s in theory,” he said. “But you can’t see it until the level of dopamine gets too low.”

Eliminating the symptoms of Parkinson’s disease doesn’t require people to be restored to 100 percent of previous dopamine levels, but only to a fraction of that.

“If you can bring dopamine up to the 40-50 percent level, you’ll see a functioning, normal person,” he said.

Currently, there is no cure for Parkinson’s and available therapies only treat the symptoms.

Major contributing factors for getting Parkinson’s disease include prolonged exposure to metals or pesticides and other environmental chemicals, according to Kanthasamy.

Symptoms of Parkinson’s disease include trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; slowness of movement; and impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. Because the disease typically affects people over the age of 50, the National Institutes of Health anticipates the incidence of Parkinson’s will increase as the nation’s population ages.

Source: Anumantha Kanthasamy
Iowa State University

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August 8, 2009 by mike.

SAN DIEGO—A simple smell test may soon be used to aid the diagnosis of Parkinson’s disease and to identify relatives and others at risk for the disease. Research on the use of smell tests in Parkinson’s disease was presented at the 58th Annual Meeting of the American Academy of Neurology.

Since at least 1955, hyposmia has been known to occur in patients with Parkinson’s disease, according to Nicolaas Bohnen, MD, Associate Professor of Radiology and Neurology at the University of Michigan in Ann Arbor. But interest in the phenomenon has grown markedly in the past few years, driven by the hope of developing neuroprotective treatment for patients in the early stage of the disorder. “The idea is to have biomarkers for early diagnosis,” said Dr. Bohnen, “and this interest is related to neuroprotective treatment.” While no definitive neuroprotective treatment has emerged, recent studies of coenzyme Q10 and rasagiline have hinted that such a therapy might be possible.

PASSING THE SMELL TEST

Dr. Bohnen’s team sought to determine whether a selective pattern of smell deficit might exist in patients with Parkinson’s disease. They used the University of Pennsylvania Smell Identification Test (UPSIT), a self-administered battery of 40 scratch-and-sniff odors ranging from turpentine to roses to pizza. The researchers compared smell ability in 26 Parkinson’s disease patients and 26 controls matched for age, sex, and smoking history.
The investigators found that patients with Parkinson’s disease did worse compared with controls on identifying eight odors (listed here in order of decreasing odor identification): licorice, coconut, banana, dill pickle, paint thinner, turpentine, cherry, and soap. Patients were better able to distinguish only one smell: lemon.

The existence of a selective deficit corroborates well with findings from a similar study in the United Kingdom, although there were some differences. In particular, British patients especially had trouble identifying wintergreen, while the American patients in Dr. Bohnen’s study had fewer difficulties in identifying this odor. “The cultural affinity for specific smells may differ between groups, as people are more exposed in daily life to specific smells,” he said. Difficulty recognizing banana was common to both groups.

“I’m unaware of any good explanation for why there is this specific deficit in Parkinson’s disease,” said Dr. Bohnen. While the disease is characterized by well-described pathology in the olfactory nucleus, “smell recognition is also a cognitive function. It’s relatively complex.”
Whatever the underlying physiology, the selective pattern may provide a reliable and easily administered biomarker for earlier diagnosis, assuming further studies confirm these results. “If a physician has a clinical suspicion, selective hyposmia could be used to help make the diagnosis,” Dr. Bohnen said. He also noted that smell testing may be more reliable than motor testing, especially for patients in the earliest stages or for those with comorbid conditions that also affect movement, such as arthritis. Early results from an ongoing study conducted by his group suggest that in first-degree relatives of patients with Parkinson’s disease, a combination of smell and cognitive testing is better at predicting a dopamine deficit than are motor tests.

CAFFEINE AND HYPOSMIA

Hyposmia in first-degree relatives of Parkinson’s disease patients also correlates with low caffeine intake, according to a third study. High caffeine consumption previously has been shown to be associated with a lower risk of Parkinson’s disease. In this study of 159 relatives of patients with Parkinson’s disease, Matthew Stern, MD, and colleagues from Pennsylvania Hospital in Philadelphia found that lifetime caffeine intake was negatively correlated with UPSIT score. Twenty-five percent of those consuming one cup or less per day of a caffeinated beverage over their lifetime were at or below the 10th percentile in UPSIT performance, compared with only 8% of those consuming more than one cup per day. “The effect may be the result of poor olfactory performance in individuals who will go on to develop Parkinson’s disease,” the researchers concluded, although they noted an alternative explanation is that hyposmia is “an intermediate phenotype” for the disease, due to the sharing of epidemiologic associations and risk factors with those for clinical Parkinson’s disease.
NR

—Richard Robinson

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March 8, 2009 by mike.

Teams of scientists from Australia and the United States have used yeast and mammalian cells to discover a connection between genetic and environmental causes of Parkinson’s disease (PD).

Yeasts are single cell organisms, used widely in biological research because their structure resembles that of cells found in animals and humans. Yeasts share many genes, or their functional equivalents, with humans and offer the ability to screen or test thousands of genes and analysing their effects.

Two genes (alpha-synuclein and PARK9) had separately been associated with forms of Parkinson’s disease, while manganese poisoning can cause PD-like symptoms in miners and welders exposed to high manganese levels. Findings connecting alpha-synuclein, PARK9 and sensitivity to manganese, made possible by yeast research, have been published online in the February issue of the prestigious international journal, Nature Genetics.

“This is the first time that we’ve been able to connect three pieces of the Parkinson’s disease jigsaw puzzle and it tells us we’re on the right track to understanding what goes wrong in this disease” said Dr Antony Cooper from Sydney’s Garvan Institute of Medical Research and head of the project group in Australia.

Parkinson’s disease involves the degeneration of neurons that produce the neurotransmitter dopamine. Autopsies show an abundance of the small protein alpha-synuclein in affected regions of the brain, so scientists have known for some time that over-expression of the protein is toxic.

When a European group discovered PARK9’s involvement in an inherited form of Parkinson’s disease they examined some of the surviving neurons from patients who had ‘sporadic’ Parkinson’s, as opposed to inherited forms of the disease, and found they contained ten times the levels of PARK9 when compared with similar parts of the brain in patients without the disease.

“It’s possible that the surviving neurons remained functional, unlike the degenerated neurons surrounding them, because high levels of PARK9 protected them in some way,” said Cooper.

“Little was known of PARK9’s function but as yeast contains an equivalent gene, we were able to analyse its function.”

“We found that high levels of the PARK9 in a cell diminish the toxic effects of alpha-synuclein. We also found that it appears to be a manganese pump, capable in theory of removing excess levels of the metal from cells.”

“We need to know what is happening at the critical early stages of the disease, so that we can stop it, but we only get to examine human brains after death, when the damage has been done. Using yeast allows us to examine the early damaging stages“

A key, and perplexing, question for researchers in the field has been whether or not there is a single cause, or related group of genetic determinants, that result in dopaminergic neuron loss, or ‘Parkinson’s disease’.

“We would love to be able to link all the genes that we know have something to do with Parkinson’s disease,” said Cooper. “If you discover there’s a central pathway involved, it provides much better potential for finding a successful treatment“

“So far, we’ve linked PARK9, alpha-synuclein and manganese toxicity. These linkages are not coincidental. They’re likely to be affecting a pathway and we suspect it’s a central pathway. To confirm that would be very exciting indeed.”

Dr Cooper has been collaborating for several years with Dr Susan Lindquist, from the Whitehead Institute for Biomedical Research and Dr Aaron Gitler, from the University of Pennsylvania School of Medicine, to find how alpha-synuclein can damage cells.

To confirm that their results were not specific to yeast alone, Gitler, Cooper and Lindquist collaborated with Associate Professor Guy Caldwell, from the University of Alabama, and Associate Professor Jean-Christophe Rochet from the University of Purdue in Indiana, who verified their results in other Parkinson model systems.

“We wanted to check our findings were relevant in other Parkinson’s models, because the more models it fits into, the more you believe it’s real,” said Cooper.

Garvan Institute
——————————————————————————–

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February 8, 2009 by mike.

By Rick Nauert, Ph.D.
Senior News Editor
Reviewed by John M. Grohol, Psy.D. on January 27, 2009

A new study offers tantalizing hope that the drug rasagiline can do what no other medication for Parkinson’s disease does — slow the progression of the devastating degenerative brain disease.

The study investigated the long-term effects of rasagiline (Azilect) on newly diagnosed patients and discovered people who began the drug earlier continued to do better than those for whom treatment was delayed six months.

A research paper, “Long-term Outcome of Early Versus Delayed Rasagiline Treatment in Early Parkinson’s Disease” was recently published in the journal Movement Disorders.

“Patients who received rasagiline right from the beginning rather than after a six-month delay experienced less progression of the clinical signs and symptoms of Parkinson’s disease that interfere with activities of daily living such as eating, walking and dressing,” said the study’s lead author Robert A. Hauser, MD.

“This is potentially consistent with a slowing of underlying disease progression, although other possible mechanisms also need to be considered.”

The study, sponsored by Teva Pharmaceutical Industries Ltd. (Israel), Teva Neuroscience, Inc. (USA) and H. Lundbeck A/S (Denmark), was a long-term open label extension of the multisite trial known as TEMPO.

In TEMPO, more than 400 untreated patients with early Parkinson’s disease were randomly assigned to rasagiline for a year (1 mg daily or 2 mg daily) or to placebo for six months followed by rasagiline for six months (2 mg daily).

At the end of a year, patients receiving rasagiline from the start fared better as measured by the Unified Parkinson’s Disease Rating Scale. They experienced less worsening of motor symptoms, such as rigidity and tremor, and had fewer problems with activities of daily living than patients who began rasagiline six months later.

The open-label extension study followed more than 300 patients from the TEMPO study for up to 6.5 years. In this extension study, all patients continued on rasagiline (1 mg. daily) and could take other Parkinson’s disease medications as needed.

The researchers found those who started rasagiline right from the beginning of the TEMPO study continued to fare better than patients in the delayed-start group. Over the course of the entire study, the early-start group had 16 percent less progression of the signs and symptoms of Parkinson’s disease, and this greater clinical benefit was observed even as patients received conventional Parkinson’s disease medications in addition to rasagiline.

Rasagiline appeared to be well tolerated in this long-term study.

If the clinical outcomes from the TEMPO and extension study hold up under further scrutiny, it may indicate that early initiation of rasagiline confers a protective effect against disease progression, Dr. Hauser said.

If this is the case, it reinforces the importance of individuals being diagnosed and treated as soon as possible.”

The study authors point out that early initiation of any drug to relieve symptoms of Parkinson’s disease may lead to a better clinical outcome compared to delayed administration — something that will be elucidated as more delayed-start studies are performed with other Parkinson’s medications.

Source: University of South Florida Health

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January 11, 2009 by mike.

Tiny capsules implanted in the brain have been developed to reverse the effects of Parkinson’s disease.
The capsules contain pig cells that produce chemicals and proteins to help repair damaged brain tissue.Early results suggest the treatment could halt the tremors and stiffness that blight Parkinson’s sufferers.
Parkinson’s is caused by the loss of nerve cells in the brain that control muscle movement.
Early signs often include tremor in one hand or arm when the body is resting, as well as muscle stiffness.
The treatment, being developed by Australian firm Living Cell Technologies, uses special cells that produce cerebrospinal fluid that appear to patch up the damaged part of the brain in Parkinson’s patients.

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