DUODOPA WITH COMT INHIBITORS FOR PARKINSON'S DISEASE

10th December 2011 - New research

European Journal of Neurology [2011] Dec 5 [Epub ahead of print] (D.Nyholm, A.Johansson, H.Lennernäs, H. Askmark)

Duodopa is a combination of L-dopa and carbidopa in the form of a gel. It is administered throughout the day using a portable pump directly into the small intestine through a surgically placed tube. This ensures a flow of L-dopa that can be adjusted according to the person's needs. It enables more consistent plasma concentrations of L-dopa. The side effects of Duodopa are similar to those observed with oral administration of L-dopa and carbidopa.

COMT inhibitors (Catechol-O-methyltransferase inhibitors) may be used to decrease the need for L-dopa, because they reduce its breakdown. COMT inhibitors have already been successfully used orally as Stalevo, which is a combination of L-dopa and carbidopa (the same as Sinemet), plus a COMT inhibitor (Entacapone). So researchers have investigated whether COMT inhibitors can also be taken orally in order to reduce the L-dopa requirement used with Duodopa. Both major COMT inhibitors (entacapone and tolcapone) were tested. The additional oral use of either of the COMT inhibitors was found to reduce the need of L-dopa by 20%. They did this without altering plasma L-dopa concentrations, reducing symptoms, or by reducing "off" time.  

SMOKING REDUCES THE RISK OF PARKINSON'S DISEASE

19th November 2011 - New research

SMOKING REDUCES THE RISK OF PARKINSON'S DISEASE

Fukuoka Igaku Zasshi [2011] 102 (8) : 254-265 (Kiyohara C, Kusuhara S.) 

Movement Disorders [2011] Nov 16 [Epub ahead of print] (Searles Nielsen S, Gallagher LG, Lundin JI, Longstreth WT Jr, Smith-Weller T, Franklin GM, Swanson PD, Checkoway H.)

The risk of developing Parkinson's Disease has been found to be far lower in people that smoke. Current smokers reduce the risk of developing Parkinson's Disease down to 31%. Those people that have ever been smokers reduce the risk down to 55%. Former smokers reduce the risk to 72%. The risk of Parkinson's Disease therefore effectively increases over time if somebody gives up smoking. These results were obtained by assessing all the possible studies concerning smoking and Parkinson's Disease. Even the risk for passive smokers was reduced to only 34%. What the results do not show is whether those people inclined to be smokers are for some reason less likely to develop Parkinson's Disease, or if smoking has an effect on the biochemistry involved in Parkinson's Disease.

Tobacco smoke contains chemicals that are MAO inhibitors. MAO inhibitors are a type of drug (such as Selegiline and Rasagiline) used commonly in Parkinson's Disease. MAO inhibitors affect Parkinson's Disease by maintaining dopamine levels. The main drug in tobacco, which is nicotine, is heavily involved in the activity of acetylcholine, a chemical in the body that affects the activity of dopamine.

PRAMIPEXOLE CLINICAL TRIAL RESULTS

Neurology [2011] 77 (8) : 767-774 (A.H.Schapira, P.Barone, R.A.Hauser, Y.Mizuno, O.Rascol, M.Busse, L.Salin, N.Juhel, W.Poewe)

Clinical trials compared the clinical efficacy in Parkinson's Disease of the more convenient to use extended-release (ER) formulation of the dopamine agonist pramipexole, and the standard immediate-release (IR) pramipexole. Pramipexole is also known as Mirapex, Mirapexin, or Sifrol. For more information go to Mirapex and Mirapex ER. In the first clinical trial, both forms of pramipexole were more effective than a placebo. Both formulations (extended release and immediate release) were similarly effective in Parkinson's Disease and were equally tolerated. In the second clinical trial, both forms of pramipexole were more effective than a placebo. Off times decreased by up to 150 minutes per day, but a placebo achieved an 84 minute reduction in off times, thereby lessening the actual reduction in off time to just over an hour per day. Immediate release pramipexole was slightly more effective than extended-release pramipexole, but otherwise, extended-release pramipexole could be readily substituted for immediate-release pramipexole.

14 November- New blog

THE DOPAMINE CHRONICLES

The Dopamine Chronicles is the new Parkinson's Disease blog of cartoonist Martin Bee. His blog specialises in Parkinson's Disease cartoons. In the words of Martin Bee "Any of you diagnosed with this disease probably can relate to the reaction. The Dopamine Chronicles is all about me continuing my art, my toons and so on. So I decided to do (almost) a cartoon a day about Parkinson’s and me." Martin Bee is a 60 year old Vietnam Veteran who was a Navy Corpsman stationed with the 1st Marine Division whilst he was in Vietnam. After leaving the Navy, he graduated in Art and then worked in design and illustration. Despite being diagnosed with Parkinson's Disease, which included a shaking right hand, he could still draw. Although Parkinson's Disease hindered his drawing technique, he altered the techniques he used in order to overcome the problems it caused him. 

TRICHLOROETHYLENE MULTIPLIES THE RISK OF PARKINSON'S DISEASE

Annals of Neurology [2011] Nov 14 [Epub ahead of print] (S.M.Goldman, P.J.Quinlan, G.W.Ross, C.Marras, C.Meng, G.S.Bhudhikanok, K.Comyns, M.Korell, A.R.Chade, M.Kasten, B.Priestley, K.L.Chou, H.H.Fernandez, F.Cambi, J.W.Langston, C.M.Tanner)

Exposure to the solvent Trichloroethylene has been found to multiply the risk of Parkinson's Disease by six times. Results were similar for estimates of exposure duration and cumulative lifetime exposure. Trichloroethylene is a solvent that is used extensively in industry and the military and is a common environmental contaminant. It has been used to extract vegetable oils, in coffee decaffeination, and in the preparation of flavouring extracts from hops and spices. Much of its use has been banned because of toxicity. Trichloroethylene is the most common organic contaminant in groundwater, and so can cause toxicity via the water supply. Around 30% of U.S. water supplies are contaminated by Trichloroethylene. For more information go to Trichloroethylene.

A previous study showed that workers with workstations adjacent to the source of Trichloroethylene and who were subjected to chronic inhalation and dermal exposure from handling Trichloroethylene soaked metal parts all had Parkinson's disease. Lesser chronic respiratory exposure to Trichloroethylene led to many features of Parkinsonism.

Dr. Robert Hauser has recently penned an outstanding paper reviewing all the new therapies in the Parkinson's disease pipeline.

Dr. Robert Hauser has recently penned an outstanding paper reviewing all the new therapies in the Parkinson's disease pipeline.  Dr. Hauser is professor at the NPF Center of Excellence at the University of South Florida in Tampa.


Int J Neurosci. 2011;121 Suppl 2:53-62.
Future Treatments for Parkinson's Disease: Surfing the PD Pipeline.
Hauser RA.
Source
Departments of Neurology, Molecular Pharmacology and Physiology, College of Medicine , University of South Florida, Tampa, Florida USA.
Abstract
ABSTRACT Our current wish list for the treatment of Parkinson's disease (PD) includes therapies that will provide robust and sustained antiparkinsonian benefit through the day, ameliorate or prevent dyskinesia, and slow or prevent the progression of the disease. In this article, I review selected new therapies in clinical development for motor features or treatment complications of PD, and some that may slow disease progression. These include adenosine 2a (A2a) antagonists (istradefylline, preladenant, and SYN115), levodopa/carbidopa intestinal gel (LCIG), IPX066-an extended-release formulation of carbidopa/levodopa, XP21279-a sustained-release levodopa prodrug, ND0611-a carbidopa subcutaneous patch, safinamide-a mixed mechanism of action medication that may provide both MAO-B and glutamate inhibition, PMY50028-an oral neurotrophic factor inducer, antidyskinesia medications (AFQ056 and fipamezole), and gene therapies (AAV2-neurturin and glutamic acid decarboxylase gene transfer). Some of these therapies will never be proven efficacious and will not come to market while others may play a key role in the future treatment of PD.

Exposure to Toxic Solvents Linked to Parkinson's Disease

HealthDay – 9 hours ago

MONDAY, Nov. 14 (HealthDay News) -- Exposure to the industrial solvent trichloroethylene (TCE) appears to greatly increase the risk of Parkinson's disease, and exposure to two other solvents also boosts the chances of developing the neurodegenerative disorder, a new study indicates.
As many as 500,000 people in the United States have Parkinson's disease and more than 50,000 new cases are diagnosed in the country each year. Some research suggests that genetic and environmental factors might trigger Parkinson's, and several studies have reported that exposure to solvents may increase the risk.
In this new study, U.S. researchers interviewed 99 pairs of elderly twins about their lifetime occupations and hobbies. Exposure to TCE was associated with a sixfold increased risk of Parkinson's disease. Exposure to perchloroethylene (PERC) and carbon tetrachloride (CCI4) were also associated with increased risk.
The study was led by researchers at The Parkinson's Institute in Sunnyvale, Calif., and was published Nov. 14 in the journal Annals of Neurology.
"Our findings, as well as prior case reports, suggest a lag time of up to 40 years between TCE exposure and onset of [Parkinson's], providing a critical window of opportunity to potentially slow the disease process before clinical symptoms appear," said Dr. Samuel Goldman and colleagues in a journal news release.
While this study focused on job-related exposure, the solvents are common in soil, groundwater and the air in the United States. For example, TCE is detected in up to 30 percent of the nation's drinking water supplies, according to the researchers.
"Our study confirms that common environmental contaminants may increase the risk of developing [Parkinson's], which has considerable public health implications," Goldman and colleagues said.
All three solvents linked to Parkinson's are used extensively worldwide and TCE is a common agent in paints, adhesives, carpet cleaners and dry-cleaning solutions. In the United States, millions of pounds of TCE are released into the environment each year.

NEUROPATHY IS COMMON IN PARKINSON'S DISEASE

November 5,2011

Neuropathy has been found to be nearly seven times more prevalent in Parkinson's Disease. Neuropathy is the malfunction of nerves throughout the body. Neuropathy can cause a pins-and-needles sensation, numbness, burning pain, loss of vibration sense, and a loss of position sense, which is not knowing where the arms and legs are. Walking and even standing can become unsteady. The effects of neuropathy can progress to far more widespread and serious symptoms. For more information go to Polyneuropathy. The researchers found that Vitamin B12 deficiency was a more common cause of neuropathy. Vitamin B12 levels were found to be significantly lower in people with Parkinson's Disease. They believed that the Vitamin B12 deficiency in Parkinson's Disease could be related to the effect of long term use of L-dopa. They consequently suggested that both Vitamin B and Vitamin B12 monitoring and supplementation, as well as serial clinical assessment for neuropathy, may be advisable in people with Parkinson's Disease..

Structure of Parkinson's disease protein identified

Tuesday, November 01, 2011

A team of researchers from the Petsko-Ringe and Pochapskylaboratories at Brandeis have produced and determined the structureof alpha-synuclein, a key protein associated with Parkinson’s disease.

Their findings, recently published in Proceedings of the National Academy of Sciences(PNAS), provide information that may someday be used to produce a newkind of treatment for the incurable degenerative brain disorder.

Alpha-synuclein is found in large quantities in the brain. Its association with Parkinson’s disease has stirred curiosity since it was discovered in 1997.

“Nobody knows what it does, but there’s a lot of it,” says Pochapsky.“The question is whether the unfolded or coagulated Lewy body proteinjust represents the pathological form of something that’s normally doingsomething.”

To explore that question, the scientists wanted to find out what theform alpha-synuclein is in before it turns into Lewy body clumps,figuring that if it is possible to stabilize, the progression ofParkinson’s disease could be either slowed or reversed.

“Even if we don’t know what it is, we at least want to know in whatform alpha-synuclein protein should be under normal conditions,” saysPochapsky.

By Susan Chaityn Lebovits
http://medicalxpress.com/news/2011-10-parkinson-disease-protein.html

Abnormal oscillation in the brain causes motor deficits in Parkinson's disease

                                          
The research group headed by Professor Atsushi Nambu (The National Institute for Physiological Sciences) and Professor Masahiko Takada (Primate Research Institute, Kyoto University) has shown that the 'oscillatory' nature of electrical signals in subcortical nuclei, the basal ganglia, causes severe motor deficits in Parkinson's disease, by disturbing the information flow of motor commands. The group also found that chemical inactivation of the subthalamic nucleus (a structure of the basal ganglia) in parkinsonian monkeys improved the motor impairments by reducing the 'oscillations.' The results of this study were reported in European Journal of Neuroscience, November 2011 issue.