Novel drug combats psychosis in Parkinson’s disease

The non-dopaminergic drug pimavanserin reduces psychotic symptoms in patients with Parkinson’s disease (PD) without worsening motor function, shows a randomized trial.

In a press statement, lead researcher Clive Ballard (King’s College London, UK) stressed that “the clinical benefits of pimavanserin were seen by patients, those caring for them, and independent blinded raters alike.”

Along with observed improvements in sleep, this suggests that tackling psychosis had “a broader effect on wellbeing of patients,” write Ballard and colleagues in The Lancet.

A total of 199 patients participated in the study, 185 of whom were included in the final analysis; all had a combined score of at least 6 on the neuropsychiatric inventory items delusions and hallucinations, or an individual score of at least 4. 

The researchers tried to provoke a placebo effect ahead of the start of drug treatment by first providing all patients with 2 weeks of psychosocial therapy. Nevertheless, patients assigned to the placebo group still had a 14% reduction in psychotic symptoms on the PD-adapted Scale for Assessment of Positive Symptoms (SAPS) over the 6-week study period.

However, patients taking pimavanserin – a selective serotonin 5-HT2A inverse agonist – had a significantly larger 37% improvement.

In an accompanying commentary, Susan Fox (Toronto Western Hospital, Ontario, Canada) writes: “Overall, the study opens up a new therapeutic avenue in treatment of Parkinson's disease psychosis.”

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62106-6/fulltext

Novel drug combats psychosis in Parkinson’s disease

Eating Peppers Tied to Lower Parkinson's Risk, Study Finds - Drugs.com MedNews

Eating vegetables that naturally contain nicotine, such as peppers and tomatoes, may reduce your risk of developing Parkinson's disease, according to a new study....

Eating Peppers Tied to Lower Parkinson's Risk, Study Finds - Drugs.com MedNews

New Drugs May Offer Hope to Parkinson's Patients - Drugs.com MedNews

"Progress is being made to expand our use of medications, develop new medications and to treat symptoms that either we haven't been able to treat effectively or we didn't realize were problems for patients," said Dr. Robert Hauser, professor of neurology and director of the University of South Florida Parkinson's Disease and Movement Disorders Center in Tampa.

Parkinson's disease, a degenerative brain disorder, affects more than 1 million Americans. It destroys nerve cells in the brain that make dopamine, which helps control muscle movement. Patients experience shaking or tremors, slowness of movement, balance problems and a stiffness or rigidity in arms and legs.

In one study, Hauser evaluated the drug droxidopa (see the structure right),  which is not yet approved for use in the United States, to help patients who experience a rapid fall in blood pressure when they stand up, which causes light-headedness and dizziness. About one-fifth of Parkinson's patients have this problem, which is due to a failure of the autonomic nervous system to release enough of the hormone norepinephrine when posture changes.

Hauser studied 225 people with this blood-pressure problem, assigning half to a placebo group and half to take droxidopa for 10 weeks. The drug changes into norepinephrine in the body.

Those on the medicine had a two-fold decline in dizziness and lightheadedness compared to the placebo group. They had fewer falls, too, although it was not a statistically significant decline.

In a second study, Hauser assessed 420 patients who experienced a daily "wearing off" of the Parkinson's medicine levodopa (see structure left), during which their symptoms didn't respond to the drug. He compared those who took different doses of a new drug called tozadenant, which is not yet approved, with those who took a placebo. All still took the levodopa.

At the start of the study, the patients had an average of six hours of "off time" a day when symptoms reappeared. After 12 weeks, those on a 120-milligram or 180-milligram dose of tozadenant (see structure below) had about an hour less of "off time" each day than they had at the start of the study.

Tozadenant, which works on brain receptors thought to regulate motor function, merits further study in future trials, Hauser said.

In another study, Hauser looked at 321 patients with early stage Parkinson's whose symptoms weren't handled well by a medicine called a dopamine agonist, typically the first drug prescribed for Parkinson's patients. During the 18-week study, Hauser assigned them to take either their usual medicine plus an add-on drug called rasagiline (brand name Azilect see below structure) or their usual medicine and a placebo.

Azilect is approved for use in patients with early stage disease as a single therapy or as an add-on to levodopa, Hauser said, but not yet as an add-on to dopamine agonists.

Those taking the Azilect   but not those taking the placebo   improved by 2.4 points on a standard Parkinson's disease rating scale.

Costs of the still unapproved drugs are not known. Azilect costs about $200 monthly at the 1-milligram daily dose used in the study.

Each of the studies was funded by the pharmaceutical company making the particular drug: Chelsea Therapeutics paid for the blood-pressure study; Biotie Therapies Inc., supported the "wearing-off" study; and Teva Pharmaceutical Industries sponsored the Azilect study. Hauser is a consultant for all three companies.

New Drugs May Offer Hope to Parkinson's Patients - Drugs.com MedNews

Promising drug slows down advance of Parkinson's disease and improves symptoms

The research team, led by senior author Jay S. Schneider, Ph.D., Director of the Parkinson's Disease Research Unit and Professor in the Department of Pathology, Anatomy and Cell Biology and the Department of Neurology at Jefferson, found that administration of GM1 ganglioside, a substance naturally enriched in the brain that may be diminished in Parkinson's disease brains, acted as a "neuroprotective" and a "neurorestorative" agent to improve symptoms and over an extended period of time slow the progression of symptoms.

What's more, once the study participants went off the drug, their disease worsened. The study enrolled 77 subjects and followed them over a 120-week period and also followed 17 subjects who received current standard of care treatment for comparison.

"The drugs currently available for Parkinson's disease are designed to treat symptoms and to improve function, but at this time there is no drug that has been shown unequivocally to slow disease progression," said Dr. Schneider. "Our data suggest that GM1 ganglioside has the potential to have symptomatic and disease-modifying effects on Parkinson's disease. If this is substantiated in a larger clinical study, GM1 could provide significant benefit for Parkinson's disease patients."

Ref : http://www.jns-journal.com/article/S0022-510X%2812%2900581-3/abstract

Promising drug slows down advance of Parkinson's disease and improves symptoms

Resveratrol might help improve mobility and prevent life-threatening falls among older people

In continuation of my update on Resveratrol...

"Our study suggests that a natural compound like resveratrol, which can be obtained either through dietary supplementation or diet itself, could actually decrease some of the motor deficiencies that are seen in our aging population," said Jane E. Cavanaugh, Ph.D., leader of the research team. "And that would, therefore, increase an aging person's quality of life and decrease their risk of hospitalization due to slips and falls."

Resveratrol might help improve mobility and prevent life-threatening falls among older people

Berries, Tea May Cut Men's Odds for Parkinson's: Study

In continuation of my update on the benefits of   berries, apple, tea...

Berries, Tea May Cut Men's Odds for Parkinson's: Study:  - Regularly consumption of food and drink rich in substances called flavonoids, such as berries, apples, tea and red wine, can lower a man's risk of developing Parkinson's disease by 40 percent, new research suggests.

Small Molecule c-jun-N-Terminal Kinase Inhibitors Blocks Brain Cell Destruction in Parkinson's Disease - a new hope !

Scientists from the Florida campus of The Scripps Research Institute have produced the first known compound to show significant effectiveness in protecting brain cells directly affected by Parkinson's disease, a progressive and fatal neurodegenerative disorder.  Although the findings were in animal models of the disease, the effectiveness of the compound, combined with its potential to be taken orally, offers the tantalizing possibility of a potentially useful future therapy for Parkinson's disease patients.  As per the claim by the lead researcher, Prof. Philip LoGrasso,   the compelling data on the first oral, brain-penetrating inhibitor to show significant efficacy in preventing neurodegeneration in both mouse and rat models of Parkinson's disease.

The new small molecule labeled SR-3306  is aimed at inhibiting a class of enzymes called c-jun-N-terminal kinases (JNK). Pronounced "junk," these enzymes have been shown to play an important role in neuron (nerve cell) survival. As such, they have become a highly viable target for drugs to treat neurodegenerative disorders such as Parkinson's disease.

The SR-3306 compound, which has been in development at Scripps Florida for several years, performed well in both cell culture and animal models. In cell culture, the compound showed greater than 90 percent protection against induced cell death of primary dopaminergic neurons, while in mouse models of induced neuron death, the compound showed protective levels of approximately 72 percent.

 "It was a surprise that level of neuroprotection reduced the behavioral impact so strongly," LoGrasso said, "but it's indicative of how it might perform in human patients. While SR-3306 doesn't represent a cure, it does appear to have the potential of stopping the progression of the disease."….

 Ref : http://pubs.acs.org/doi/pdfplus/10.1021/cn100109k

Memantine for Huntington's disease ?

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA glutamate receptors. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Memox by Unipharm.

Now researchers from Burnham & University of California have found that, Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity.

Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein. The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins. However, excessive extrasynaptic activity contributed to increased nerve cell death. The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity.

This finding is of great importance because of the fact that chronic neurodegenerative diseases like Huntington's, Alzheimer's and Parkinson's are all related to protein misfolding and the researchers have shown for the first time that that electrical activity controls protein folding, and if one has a drug that can adjust the electrical activity to the correct levels, one can protect against misfolding and also the research verifies that appropriate electrical activity is protective. They also found that normal synaptic activity was protective. Subsequently, they treated Huntington's disease model mice with both high and low doses of Memantine and found that the low doses were protective by blocking pathological extrasynaptic activity, while high-dose Memantine encouraged disease progression because it also blocked the protective synaptic NMDA receptor activity. Its really good achievement congratulations. After having small clinical trials, larger, international clinical trials are now being planned....


Source : http://www.eurekalert.org/pub_releases/2009-11/bi-rfp111309.php.

Statins as anticancer and anti diabetic agents ?

We know that statins are widely used as cholesterol lowering drugs. They act by inhibiting HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway that leads to the synthesis of farnesyl pyrophosphate, a precursor for cholesterol synthesis and the source of lipid moieties for protein prenylation. But researchers from University of Gothenburg, have found that statins might be useful as anticancer and antidiabetic too.

Statins lower cholesterol by blocking certain enzymes involved in our metabolism. However, they have also been shown to affect other important lipids in the body, such as the lipids that help proteins to attach to the cell membrane (known as lipid modification). Because many of the proteins that are lipid-modified cause cancer, there are now hopes that it will be possible to use statins in the treatment of cancer.

Studies show that statins can have a dramatic inhibitory effect on growth and development. As the researchers managed to identify the enzyme involved, they can also explain how the effect arises at molecular level. Not least that they can prevent the growth of cancer cells caused by lipid-modified proteins, but also that they can be effective in the treatment of diabetes and neurological disorders such as Parkinson's. In one of my earlier blog, I have mentioned about the simvastin (Simvastatin prevents progression of Parkinson's Disease ?).

So in the days to come statins may be useful as anticancer, anti diabetic and even to treat Parkinsons disaese....


Source : http://www.science.gu.se/english/News/News_detail/Cholesterol-lowering_medicines_may_be_effective_against_cancer.cid898016

Simvastatin prevents progression of Parkinson's Disease ?

About Simvastin :
Simvastatin, (marketed under the names Zocor, Simlup, Simcard, Simvacor) is a hypolipidemic drug belonging to the class of pharmaceuticals called "statins". It is used to control hypercholesterolemia and to prevent cardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus. When I was working with Bangalore based company, the sister company was working on it and now its marketing too.

Recently researchers from the Rush University, have found an interesting fact that Simvastin, may prevent Parkinson's disease from progressing further. 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.

If the researchers 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. Hope some relief to the sufferers of Parkinson disease....

Ref : http://www.rush.edu/webapps/MEDREL/servlet/NewsRelease?id=1304

Epilepsy Drugs Could Treat Alzheimer's And Parkinson's

Epilepsy Drugs Could Treat Alzheimer's And Parkinson's