PARKINSON'S DISEASE NEWS

AUGUST 2007

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31st August 2007 : New research

DOES MANGANESE EXPOSURE REALLY CAUSE PARKINSON'S DISEASE ?

Journal of Toxicological and Environmental Health (Part B - Critical Reviews) [2007] 10 (6) : 417-465 (Santamaria AB, Cushing CA, Antonini JM, Finley BL, Mowat FS.) Complete abstract

Recent studies report that exposure to manganese, an essential component of welding and some steels, results in neurotoxicity or Parkinson's Disease in welders. This review presents a critical analysis of the published studies that were conducted on a variety of Manganese exposed occupational cohorts during the last hundred years, and the regulatory history of Manganese and welding fumes. Data indicates that Manganese exposures in welders are less than those associated with the reports of manganism in miners and smelter workers. It was also found that although manganism was observed in very highly exposed workers, that the scant exposure data available for welders do not support a conclusion that welding is  associated with  neurotoxicity.

PSYCHIATRIC EFFECTS OF DBS SURGERY IN PARKINSON'S DISEASE

Movement Disorders [2007] Aug 22; [Epub ahead of print] (Appleby BS, Duggan PS, Regenberg A, Rabins PV.)
Complete abstract

Deep brain stimulation (DBS) has been approved by the FDA for use in the treatment of Parkinson's disease, essential tremor, and dystonia. Case reports and case series have reported significant psychiatric side effects in some individuals. The goal of this study was to assess the benefits and psychiatric risks of DBS. A search was conducted on PubMed, EBSCO, and PsycInfo that covered the time period 1 Jan 1996-30 Dec 2005.

98.2% of studies that assessed motor function reported some level of improvement. Most reported side effects were device or procedure related (e.g., infection and lead fracture). The prevalence of depression was 2-4%, mania 0.9-1.7%, emotional changes 0.1-0.2%, and the prevalence of suicidal ideation/suicide attempt was 0.3-0.7%. The completed suicide rate was 0.16-0.32%. In conclusion, DBS has effect in Parkinson's disease, dystonia, and essential tremor, but there is a high rate of suicide in patients treated with DBS.

29th August 2007 : News report

PARKINSON'S GOGGLES

About 40% of people with Parkinson's disease suffer from gait freeze, walking difficulties, difficulty turning corners, small shuffling steps. They may also find it hard to cross thresholds, and so freeze if the floor surface or colour  changes. Parkinson's goggles are designed to help patients feel like they are walking on a steady floor.

The goggles have a sensor that activates an LCD screen to show patients a tile pattern on the floor. The checkerboard pattern projected on the floor makes them feel like they have something to step over. There is also an auditory feedback cue. The goggles are still being tested. About 10 patients have tried them so far in this study, and the goal is 20 people. Patients in the study wore the goggles for a half hour a day for two weeks, and some seem to still see the tiles after they take off the goggles. For more information go to the Complete article.

28th August 2007 : News report

Transdermal Rotigotine as Safe and Effective as Pramipexole

A transdermal patch system with rotigotine, a dopamine agonist, appears safe and shows efficacy comparable with pramipexole and better than placebo for people with advanced Parkinson's disease say researchers. The abdominal patch application, recently licensed in Europe for use in early and late Parkinson's Disease, has been shown to provide maintained mean plasma rotigotine concentrations. The primary efficacy measure was mean decrease  in hours per day in "off" time, with equivalent significant improvements over placebo (0.88) maintained for pramipexole (-2.8) and rotigotine (-2.5). The time spent "on without troublesome dyskinesis" (hours/day) was increased over placebo (1.5) for both pramipexole (3.0) and rotigotine (3.1). The frequencies of adverse events were similar across the three treatments.

Those most common for rotigotine were nausea (17%), dyskinesia (12%), somnolence (12%), and application-site erythema/pruritus (9%). The work was carried out for Schwarz Pharma, who are developing transdermal rotigotine. For more information go to the Complete article. This study was published in Lancet Neurology [2007] 6 : 513-530 (Poewe WH, Rascol O, Quinn N et al)  Complete abstract. Unfortunately, the problem with all dopamine agonists is that they become progressively counterproductive because they decrease the sensitivity of  the  dopamine receptors that they initially stimulate.

24th August 2007 : New research

L-DOPA METABOLITE WORSENS PARKINSON'S DISEASE

Neurochemical research [2007] August 24th [Epub ahead of print] (Lee ES, Chen H, King J, Charlton C.)  Complete abstract

The cause of the L-dopa's adverse effects has not been established to date. 3-O-methyldopa (3-OMD), which is a major metabolite of L-dopa, was tested to determine whether it plays a role in the adverse effects. 3-OMD impaired locomotor activities by decreasing movement time, total distance, and number of movement by 70%, 74% and 61%, respectively.

It decreased the dopamine turnover rate by 40%, and inhibited dopamine transporter and uptake. 3-OMD induced cytotoxic effects via oxidative stress and decreased mitochondrial membrane potential, indicating that it can also damage neuronal cells. 3-OMD also potentiated L-dopa toxicity. Therefore, L-dopa treatment can accelerate the progression of Parkinson's Disease because of its metabolite 3-O-Methyldopa.

23rd August 2007 : New research

COFFEE AND TEA LOWER THE RISK OF PARKINSON'S DISEASE

Movement Disorders [2007] August 21st [ahead of print] (Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J.)  Complete abstract

Several prospective studies have assessed the association between coffee consumption and Parkinson's disease risk, but the results were inconsistent. A massive study was carried out in Finland on nearly 30,000 subjects. They examined the association of coffee and tea consumption with the risk of Parkinson's Disease.  There was a clear trend in both men and women for coffee drinkers to be less prone to Parkinson's Disease.  In both sexes combined, the multivariate-adjusted likelihood for subjects drinking 3 or more cups of tea per day compared to non-tea drinkers also showed a clearly lower risk of Parkinson's Disease.

23rd August 2007 : New clinical trial

NEW CLINICAL TRIAL OF THE JACOBSON RESONATOR

This study will evaluate a new non-invasive, non significant risk device therapy as a supplemental symptomatic treatment for Parkinson’s Disease. For more information go to the  Complete article. The device utilizes technology involving extremely low level electromagnetic fields (EMF) to provide whole body immersion. EMF treatment with the Jacobson Resonator is a new technology. For more information go to Magnetic therapy. It has shown promising results in a Phase I pilot study earlier in 2007, which preceded this Phase II study.                           

23rd August 2007 : News report

FDA CONSIDER FIRST ADULT STEM CELL TRIALS FOR PARKINSON'S DISEASE

Biopharmaceutical company BrainStorm Cell Therapeutics has arranged a meeting with the U.S. Food and Drug Administration (FDA) to coordinate clinical trials for its flagship product for the treatment of Parkinson's disease. The company said it aims to be the first worldwide to win approval to conduct trials using adult stem cells taken from patients. BrainStorm has hired Dr Andra E.Miller, director of cell and gene therapies of the Biologics Consulting Group Inc. to handle the FDA negotiations. For more information go to the Complete article.

22nd August 2007 : News report

SAFINAMIDE FAILS IN CLINICAL TRIALS

Merck and Newron plan further tests on their safinamide drug for Parkinson's disease with a lower dose after a late trial showed a higher dose lacked any significant effect. The 18-month clinical trial pooled data from patients taking both the 50-100 mg and 150-200 mg doses who had had the disease for less than five years. "The primary endpoint, time to intervention, did not reach statistical significance when data from both safinamide dose groups were pooled," the companies said in a statement.

They said their analysis showed that the lower doses of safinamide alongside dopamine led to improvements and reduced the need to make changes to treatment regimes. "Additional Phase III studies are planned to further assess the efficacy of this dose of safinamide," they added.  For more information go to the  Complete article. Safinamide has a novel dual mechanism of action based on the enhancement of the dopaminergic function (through potent, reversible inhibition of MAO-B, and dopamine uptake) and reduction of glutamatergic activity by inhibiting glutamate release. For more information go to Safinamide.

19th August 2007 : New research

GDNF FAILS TO HAVE ANY BENEFIT IN PARKINSON'S DISEASE

Acta Neurochirurgica Supplement [2007] 97 (Part 2) : 135-154 (N.K.Patel, S.S.Gill) Complete abstract

Amgen previously carried out a trial using GDNF. Patients claimed it to be a cure. Despite ongoing protests, Amgen ceased its use because they claimed it was toxic and ineffective. For more information go to  Complete article.  GDNF is a neurotrophic factor - a protein that regulates neuronal survival, differentiation, growth and regeneration. It is  claimed to represent an alternative for treating dopaminergic neurons in Parkinson's Disease but is difficult to administer clinically because it does not pass through the blood-brain barrier. 

In an independent trial in England, continuous GDNF infusion in five patients showed good tolerance, few side effects and clinical benefit within 3 months of treatment. The clinical improvement was sustained and progressive.  A second clinical trial in ten patients also showed a greater than 30% bilateral benefit in both on and off-medication score at 24 weeks. A randomized controlled clinical trial was recently conducted to confirm the previous clinical trial results. However, GDNF infusion over 6 months did not confer the predetermined level of clinical benefit. The researchers suggest that technical differences between the recent trial and previous studies contributed to this negative outcome.

15th August 2007 : News report

TWO PARKINSON'S DISEASE DRUGS CAUSE HEART RISKS

Two drugs used to treat Parkinson's Disease have been found to cause damage to heart valves. The drugs, pergolide (Permax) and cabergoline (Dostinex or Cabaser), are dopamine agonists.  Researchers looked at the medical records of 11,417 patients who had received Parkinson's drugs between 1988 and 2005.

They found that pergolide and cabergolide increase the risk of a heart valve condition by 7 and 5 times, when compared to another Parkinson's Disease drug. Patients on Parkinson's drugs besides these did not increase their risk of developing the condition.  Permax had already been withdrawn from sale in the U.S.A.. For full details go to the  Complete article. Canadian Health Authorities have now ordered the cessation of the sale of Permax in Canada.  For full details go to the  Complete article.

14th August 2007 : New resource

PARKINSON'S DISEASE BLOG NETWORK

The Parkinson's Disease Blog Network is a new Parkinson's Disease resource set up to centralize Parkinson's Disease blogs. It was developed and is maintained by Incendia Health Studios, an inVentiv Health company. It has been designed to serve as a real-time, virtual Parkinson's disease discussion and community forum, allowing users to exchange information and thoughts on topics ranging from symptoms to diet and treatment. All blogs registered on the network are listed with a brief descriptor and assigned to one of three categories : resource, medical or personal. Each includes spaces for user comments, a five-point rating scale, and tracks the number of "views". This enables the blogs found to be the most useful to be the most prominently featured. For their web site go to the Parkinson's Disease Blog Network

14th August 2007 : News report

OVER 60% OF NEWLY DIAGNOSED RECEIVE NO DRUG TREATMENT IN THE FIRST YEAR

Decision Resources, one of the world's leading research and advisory firms found that 61 percent of newly diagnosed Parkinson's disease patients do not receive any drug treatment in the first year of diagnosis. According to the new report it is likely that this occurs as a result of patients' decisions to delay treatment until symptoms become sufficiently troublesome. Furthermore, patients may be reluctant to begin L-dopa therapy, knowing that side-effects will arise. For full details go to the  Complete article.

13th August 2007 : New books

PARKINSON'S DISEASE and related disorders (PARTS 1 AND 2)

William C.Koller, Eldad Melamed

The two volumes on Parkinsons disease in the Handbook of Clinical Neurology cover the dramatic advances in understanding of the biochemical background of Parkinsonism and the resulting developments in its pharmacological management. These volumes give an account of the subject for both clinical neurologists and those researching in the neurosciences. Part I covers the scientific background, general aspects of Parkinson's disease, clinical aspects and etiology. Part II covers the medical and surgical treatment of Parkinsons disease, complications of therapy and the other parkinsonian syndromes. For details of Part I go to Book details. For details of Part II go to Book details.

13th August 2007 : New research

IS PARKINSON'S DISEASE DUE TO A LOSS OF TWO CELL TYPES RATHER THAN ONE ?

Authors of new research are claiming that the loss of two types of brain cells - not just one as previously thought - may trigger Parkinson's disease. The evidence, based on mouse models, shows a link between the loss of both norepinephrine and dopamine neurons and the delayed onset of symptoms associated with Parkinson's disease.

They suggest that it's possible that simultaneously treating both the dopamine and norepinephrine loss could further ameliorate Parkinson's disease. For full details go to the  Complete article. The results will be published in the Proceedings of the National Academy of Sciences, Early Edition online during the week of August 13th-17th. Although the authors claim that there is loss of dopamine producing cells in Parkinson's Disease, no research has ever shown this. Dopamine producing cells have only ever been shown to reduce their activity in Parkinson's Disease. Also, norepinephrine is made via the same biochemical means as dopamine, so it is obvious that a lack of dopamine will be associated with a lack of norepinephrine.

12th August 2007 : New research

DOES URIC ACID LOWER THE CHANCE OF GETTING PARKINSON'S DISEASE ?

American Journal of Epidemiology  [2007] - Advance Access published online (MG Weisskopf, E O'Reilly, H Chen, MA Schwarzschild and A Ascherio)

In 1996 scientists reported that men with above average serum uric acid levels had a 40% reduction in their likelihood of later developing Parkinson's disease Abstract. The scientists suggested that the antioxidant properties of uric acid might protect against oxidative damage and nerve cell death in Parkinson's Disease. A recent follow up study, using a larger population showed that participants with the highest uric acid levels had a 55% lower likelihood of developing Parkinson's Disease than those participants with the lowest uric acid levels Abstract. The principal investigator consequently claimed that uric acid could become the first biomarker of Parkinson's disease. For full details go to the  Complete article.

However, there is only a general tendency for Parkinson's Disease to be associated with uric acid levels. Uric acid levels could therefore not determine whether or not somebody had or would have Parkinson's Disease. Also, the reason for this association is likely to be different from the explanation given. High protein diets, likely to produce uric acid, are also high in the L-dopa precursors L-tyrosine and L-phenylalanine.  L-tyrosine and L-phenylalanine would lessen the tendency towards Parkisnon's Disease because they can increase dopamine levels. For more information on Uric acid.

11th August 2007 : News report

Michael J. Fox Foundation Announces $1.2 Million in Funding

The Michael J. Fox Foundation for Parkinson's Research announced $1.2 million in awards to four research teams working in the drug development pipeline.  The research projects will be : the autophagy pathway, a cellular pathway involved in clearing away protein such as alpha-synuclein; optimizing administration of the compound MX-4565, a non-feminizing estrogen analog that has been shown to be effective in protecting nerve cells from toxic stresses; the potential of the protein osteopontin as a Parkinson's Disease treatment; and a molecule called fisetin, which can maintain levels of glutathione, which is produced naturally as a defence against oxidative stress.

9th August 2007 : New clinical trial

CREATINE TO BE TESTED AS A TREATMENT FOR PARKINSON'S DISEASE

Creatine is an acid naturally produced by the body for regulating cell energy. For more information go to Creatine. Because some evidence suggests it may have antioxidant properties, creatine is also marketed as a nutritional supplement. Avicena Group, Inc. a biotechnology company are supplying the creatine and a placebo for a NINDS study involving 1,720 patients.

The drug being tested is significantly different from over-the-counter creatine supplements. Efficacy will be determined over 5 to 7 years by means of tests that measure ability to walk, carry out other daily activities, cognitive function, and general quality of life. For full details go to the Complete article. There are weaknesses in this study. Even in theory creatine does nothing to raise dopamine levels, which is the fundamental aim in Parkinson's Disease. There is no need to take creatine because the body can make its own from common dietary substances. In previous studies, creatine was not really found to be  effective  in Parkinson's Disease.

8th August 2007 : News report

FDA APPROVE HIGHER DOSE OF STALEVO FOR PARKINSON'S DISEASE

The U.S. Food and Drug Administration (FDA) has approved a new higher dose strength of  Stalevo (carbidopa, levodopa and entacapone). Stalevo is indicated for Parkinson's disease patients with signs and symptoms of end-of-dose "wearing off." The approval of the higher 200mg Stalevo (50 mg carbidopa, 200 mg levodopa, 200 mg entacapone) gives physicians greater dosing flexibility in the treatment of patients experiencing symptom re-emergence due to end of dose wearing off. The new dosage strength may lessen the burden of managing multiple medications. For full details go to the Complete article. For more information on  Stalevo.

7th August 2007 : New research

PREDICTORS OF FREEZING IN PARKINSON'S DISEASE

Movement Disorders [2007] 22 (7) : 953-956 (Macht M, Kaussner Y, Moller JC, Stiasny-Kolster K, Eggert KM, Kruger HP, Ellgring H.)  Complete abstract

A survey of over 6000 Parkinson's disease patients were examined for the relationship between freezing and age, gender, duration, subjective severity of Parkinson's disease, and antiparkinsonian medication. 47% of people with Parkinson's Disease reported experiencing freezing regularly. Freezing was associated with longer disease duration and the more advanced stages of Parkinson's Disease. Freezing episodes were more likely in men than in women. Freezing was more common in patients taking, in addition to L-dopa, Entacapone, Amantadine, or dopamine agonists. Patients considering tremor as their main symptom reported freezing less frequently. Common Parkinson's Disease drugs given in combination with L-dopa were not negatively related to episodes of  freezing.

Movement Disorders [2007] 22 (7) : 1046-1050 (Khedr EM, Rothwell JC, Shawky OA, Ahmed MA, Foly N, Hamdy A.) Complete abstract

2nd August 2007 : New research

How Alpha-Synuclein can cause Parkinson's Disease  

Neuroscience Bulletin [2007] 23 (1) : 53-57 (Gao N, Li YH, Li X, Yu S, Fu GL, Chen B.) Complete abstract

Alpha synuclein has been known to increase Parkinson's Disease, but the means has not been known. New research has shown that alpha-synuclein genetically interferes with the formation of tyrosine hydroxylase. Tyrosine hydroxylase is the enzyme needed to form dopamine via the following means L-tyrosine > L-dopa > dopamine. Dopamine formation is essential for the relief of Parkinson's Disease. So Alpha Synuclein causes Parkinson's Disease symptoms by reducing dopamine formation. For more information on Alpha-Synuclein

 

1st August 2007 : New research

Is L-dopa also good for Restless Legs Syndrome ?  

Movement Disorders [2007] Jul 20; [Epub ahead of print] (Conti CF, de Oliveira MM, Andriolo RB, Saconato H, Atallah AN, Valbuza JS, Coin de Carvalho LB, do Prado GF.) Complete abstract

The treatment of Restless Legs Syndrome using L-dopa has been claimed. An assessment was made of all the clinical trials that had used L-dopa for Restless Legs Syndrome. Nine eligible clinical trials were included. The subjective analyses of these studies showed contradictory results, but the objective analyses showed that treatment group had a statistically significant improvement of periodic leg movement (PLM) index, favouring the treatment group. The most common adverse event seen was gastrointestinal symptoms. The short-term treatment with L-dopa was effective and safe for PLM, but there were only a few trials assessing long-term treatment in RLS. As the assessment gave inconclusive results, it suggests that Restless Legs Syndrome is not simply due to a lack of L-dopa and dopamine as has been theorised. For more information on Restless Legs Syndrome

 

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