APRIL 2008   


29th April 2008 - News release

spheramine - retinal cell therapy for Parkinson's Disease

It has been claimed that a novel cell therapy using retinal pigment epithelial (RPE) cells called Spheramine can improve the symptoms of people with Parkinson’s disease. The cellular product, called  Spheramine, consists of retinal pigment epithelial (RPE) cells attached attached to tiny gelatin bead microcarriers implanted in the brain. The microcarriers are necessary for the cells to survive in the brain. For more information go to Spheramine.  RPE cells, despite being in the eye, also produce L-dopa, the precursor of dopamine whose deficiency usually causes Parkinson's Disease. The implanted cells serve as a new potential source of L-dopa to enhance dopamine production.

A pilot study was initiated that followed 6 patients with moderate to advanced Parkinson's Disease to investigate the safety, tolerability, and efficacy of the Spheramine implantation. They found no Spheramine-related serious adverse events. The researchers reported a 44% reduction in symptoms, and a 23% improvement in quality of life. Results from the pilot study have prompted the initiation of a larger clinical. For more information go to the News release. The method does not account for the fact that it is insufficient dopamine formation rather than a lack of dopamine producing cells that is known to cause Parkinson's Disease. 

                                                                                                                                                     26th April 2008 - New research

sleep problems in Parkinson's Disease

Movement Disorders [2008] 23 (1) : 35-41 (Verbaan D, van Rooden SM, Visser M, Marinus J, van Hilten JJ.) Complete abstract

Researchers evaluated nighttime sleep problems and daytime sleepiness in people with Parkinson's disease. Over 400 people with Parkinson's Disease were compared to controls. Compared to controls, a significantly greater proportion of people with Parkinson's Disease had excessive daytime sleepiness, excessive nighttime sleep problems, or used sleep medication.

People with Parkinson's Disease were no different from other regarding falling asleep. Women with Parkinson's Disease experienced more nighttime sleep problems than men. Depressive symptoms were the greatest cause of differences between people with Parkinson's Disease and others. Nighttime sleep problems were related to dopamine-agonist and L-dopa dose. Daytime Sleepiness was increased with age, dopamine-agonist dose, and the severity of Parkinson's Disease. Nighttime sleep problems and daytime sleepiness occur frequently in Parkinson's Disease, with excessive daytime sleepiness being reported more commonly than nighttime sleep problems.

                                                                                                                                                                              24th April 2008 - New research

Anti-Oxidant Therapy fails Again in Parkinson's Disease

The anti-oxidant mitoquinone (MitoQ) failed to show any benefit in Parkinson's disease. Mitoquinone, a drug that is a highly potent derivative of coenzyme Q10, was completely ineffective in a clinical trial. The drug combines ubiquinone, the anti-oxidant portion of the coenzyme Q10 molecule, with a lipophilic triphenylphosphonium cation.

The resulting agent is a thousand times more potent than coenzyme Q10 in protecting cells from oxidative damage. Yet Parkinson's Disease patients taking mitoquinone experienced worse side effects and greater deterioration than patients taking a placebo. The side effects experienced included nausea, which affected 85% of patients. Vomiting and diarrhea occurred in 52% and 26% of patients respectively. The researchers said that anti-oxidants can no longer be considered a practical treatment approach. Idiopathic Parkinson's Disease has long been known to be due to insufficient dopamine rather than oxidative damage. For more information go to the Complete article. Last year, a clinical study using coenzyme Q10 also found no evidence of efficacy in Parkinson's disease. For more information go to the Complete article.


23rd April 2008 - New review


Fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X chromosome. Fragile X Syndrome is the most common form of hereditary mental retardation. Carriers of premutation (CGG) expansions of the fragile X gene are generally thought to be spared most of the problems associated with the full mutation. However, a recently discovered neurological disorder - FXTAS (Fragile X-associated Tremor/Ataxia Syndrome) - involving progressively severe tremor and difficulty with walking and balance, appears to specifically affect some older pre-mutation carriers. They are often oblivious to the fact that they are carriers and that they have symptoms of FXTAS rather than Parkinson's Disease, because the symptoms can coincide. For more information go to FXTAS.

The disorder affects at least a third of male carriers over 50 years of age. Older men were much more likely to develop symptoms. Especially prone are those men who have grandchildren with Fragile X Syndrome, because that makes it more likely that they are a carrier of the mutation. Women are hardly affected. Tremor is usually the first symptom to appear, most typically at around 60 years of age, but often earlier. Tremor is usually followed by ataxia (incoordination), then proneness to falling. Males were more agitated, aggressive, depressed, apathetic, disinhibited, and irritable. There is also impairment of intellectual functioning, that is eventually on a scale similar to that seen in Alzheimer's Disease. In those female carriers without the core features (tremor, and difficulty with walking and balance), there were more complaints of chronic muscle pain, and history of tremor than is normal.


21st April 2008 - New research

which is better - l-dopa or dopamine agonists ?

Cochrane Database of Systematic Reviews [2008], Issue 2 (Stowe RL, Ives NJ, Clarke C, van Hilten J, Ferreira J, Hawker RJ, Shah L, Wheatley K, Gray R.)  Complete abstract

Dopamine agonists are being increasingly used as a primary treatment for Parkinson's disease, but there remains uncertainty about their clinical effectiveness relative to L-dopa. This study aimed to quantify more reliably the benefits and risks of dopamine agonists compared to placebo or L-dopa in early Parkinson's disease.

The researchers analysed all relevant clinical trials. Patients taking dopamine agonists were less likely develop dyskinesia, dystonia and motor fluctuations. However, various "non-motor" side effects were all increased when taking dopamine agonists.  These included oedema, somnolence, constipation, dizziness, hallucinations and nausea. People taking dopamine agonists were also much more likely to discontinue treatment due to adverse events. Symptom control of Parkinson's Disease was better with L-dopa than with dopamine agonists.


20th April 2008 - New research

Non-motor symptoms as the first symptoms of parkinson's disease

Movement Disorders [2008] 23 (1) : 101-106 (O'Sullivan SS, Williams DR, Gallagher DA, Massey LA, Silveira-Moriyama L, Lees AJ.) Complete abstract

Non-motor symptoms (NMS), those that did not concern physical movement, are a well recognized component of the clinical picture in some patients. However, the prevalence of non-motor symptoms as the initial symptoms in proven cases of Parkinson's Disease was unknown. Over 400 people with Parkinson's Disease were assessed for their initial symptoms. Over 20% of people with Parkinson's Disease were found to have initial symptoms that were non-motor symptoms instead. The most frequent symptoms that initiated Parkinson's Disease in those people were pain (15%), urinary dysfunction (3.9%), anxiety or depression (2.5%).

When the initial symptoms were non-motor symptoms, there was a delayed diagnosis of Parkinson's Disease, most probably because the non-motor symptoms can occur because of other medical disorders. These people were more likely to be misdiagnosed and were more commonly referred to orthopaedic surgeons or rheumatologists rather than neurologists. The initial symptoms being non-motor symptoms does not affect the subsequent response to Parkinson's Disease drugs, but is associated with shorter disease duration.


19th April 2008 - News release

altropane - a new diagnostic drug for Parkinson's disease

Alseres Pharmaceuticals are beginning Phase III clinical trials on Altropane, which is an investigational, diagnostic drug developed by Alseres to enable doctors to distinguish Parkinsonian Syndromes from non-Parkinsonian Syndromes in patients with tremor. There is presently a 20%-30% rate of misdiagnosis in Parkinson's Disease, that has resulted in many people presently being treated for Parkinson's Disease that don't even have it. The presence of tremor is the main cause of misdiagnosis.

SPECT imagingAltropane is a molecular imaging agent that specifically binds to the dopamine transporter (DAT) protein found on the surface of dopamine-producing neurons, making it visible during  "SPECT" imaging. Since most forms of Parkinsonian Syndromes result in the decreased activity of dopamine-producing cells, it would be expected that these patients also have fewer DATs (dopamine transporter proteins) than do patients without Parkinsonian Syndromes. Patients could be distinguished because Non-Parkinsonian patients would have more Altropane-binding visible in the SPECT image, while Parkinsonian patients would have less. For more information go to the Complete article.

It is not explained why an additional diagnostic tool, such as a drug, is actually needed to be used with SPECT imaging, when SPECT imaging is already more than 98% reliable in diagnosing Parkinson's Disease. The medical disorders distinguished by Altropane are no different from those that  SPECT imaging already distinguishes. For more information got to Functional brain imaging.


18th April 2008 - New research

genetic Parkinson's disease goes back 2,500 years

Annals of Neurology [2008] Apr 15 [Epub ahead of print] (Ross OA, Wu YR, Lee MC, Funayama M, Chen ML, Soto AI, Mata IF, Lee-Chen GJ, Chen CM, Tang M, Zhao Y, Hattori N, Farrer MJ, Tan EK, Wu RM.) Complete abstract

Neurology [2008] 70 (16 Pt 2) : 1456-1460 (Haugarvoll K, Rademakers R, Kachergus JM, Nuytemans K, Ross OA, Gibson JM, Tan EK, Gaig C, Tolosa E, Goldwurm S, Guidi M, Riboldazzi G, Brown L, Walter U, Benecke R, Berg D, Gasser T, Theuns J, Pals P, Cras P, De Deyn PP, Engelborghs S, Pickut B, Uitti RJ, Foroud T, Nichols WC, Hagenah J, Klein C, Samii A, Zabetian CP, Bonifati V, Van Broeckhoven C, Farrer MJ, Wszolek ZK.) Complete abstract

There are a number of genetic causes of Parkinson's Disease. A large study amongst Han Chinese showed that one of these genetic mutations, LRRK2 (leucine-rich repeat kinase 2) nearly doubled the risk of Parkinson's Disease, and that the genetic mutation goes back around 2,500 years.

The study proved two points - that genetic Parkinson's Disease increases the likelihood of Parkinson's Disease rather than inevitably causes it, and that Parkinson's Disease goes back thousands of years. Another study showed that people with a form of that genetic Parkinson's Disease (LRRK2) appeared to be no different from people with idiopathic Parkinson's Disease, in age of onset and clinical features. So people would not readily know whether or not they had genetic Parkinson's Disease, or that the development of their symptoms had been genetically more likely since they were born.


17th April 2008 - New research


Sinemet consists of L-dopa and Carbidopa (a dopa decarboxylase inhibitor that  helps to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons). Stalevo consists of L-dopa, Carbidopa and Entacopone (Comtan). Entacapone (Comtan) inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. At present, the Stalevo combination is approved by the FDA for use in patients who suffer a wearing off of the effect of the Sinemet combination. Sinemet and Stalevo were compared for their therapeutic effects. The change in activity of daily living scores was a bit better with Stalevo. Physician-rated improvements were 25% higher with Stalevo. Clinical Global Impression scores were marginally better with Stalevo, as were daily living and motor subscales of the Unified Parkinson's Disease Rating Scale. Overall adverse events were more common with the Stalevo combination than with the Sinemet combination, but serious adverse events were similar for the two products. The difference was primarily in nausea (26.6% versus 13.5%) and diarrhea (8.7% versus 2.8%).

Motor complications tended to be less common with the Stalevo combination. Dyskinesia occurred in 5.3% of Stalevo patients and 7.4% of Sinemet patients. The study author claimed that the findings provide the basis for Novartis, who market the Stalevo combination in the U.S.A., to apply for use of Stalevo for early Parkinson's disease as well. This study was published as an abstract and presented at a conference. For more information go to the Complete article.

                                                                                                                                                     15th April 2008 - New research

using inosine to increase urate  to reduce Parkinson's disease

American Journal of Epidemiology [2008] 167 (7) : 831-838 (Gao X, Chen H, Choi HK, Curhan G, Schwarzschild MA, Ascherio A.) Complete abstract

End-of-dose wearing off was seen in 13.9% versus 20%, respectively (P=0.09). The Michael J. Fox Foundation announced a $5.6 million award for a Phase 2 clinical trial to investigate the potential of inosine - a naturally occurring chemical that gives rise to urate in the body - to slow or stop the progression of Parkinson's disease. For more information go to the Complete article. Urate is a natural metabolite and antioxidant in humans. Inosine is widely available to consumers in dietary supplement form. Inosine is able to forum urate, which is why it is being proposed to increase urate levels. For more information go to Urate formation.

A recent large study confirmed that higher dietary urate was associated with a lower risk of Parkinson's Disease Disease. The authors consequently suggest that dietary changes expected to increase plasma urate level may contribute to a lower risk of Parkinson's Disease. However, no rationale has been provided by the authors that would explain the link. The evidence to date surrounding inosine and Parkinson's Disease does not prove a cause-effect relationship.  Also, elevated urate levels are known to cause health risks, only some of which have been characterized to date.


14th April 2008 - New book

Parkinson's Disease and Other Movement Disorders

Mark Edwards, Niall Quinn and Kailash Bhatia

Publisher's description : Movement disorders are a group of neurological conditions that are characterised by problems with movement. Parkinson's disease is the most common of these conditions. Its treatment is complex, but effective, and there have been many recent exciting developments in the field. Other movement disorders are less common and extremely diverse, so it is difficult for practitioners to become proficient in diagnosing and treating them all. This book will help neurologists and other clinicians in the recognition and treatment of this group of disorders. Written in a concise, easy-to-use handbook format, it should appeal to a multidisciplinary audience. The text is accompanied by a DVD. Click here for more details  


12th April 2008 - News report


Eisai have been clinically testing Perampanel (E2007), which is an orally administered, highly selective non-competitive AMPA-type glutamate receptor antagonist, for use in Parkinson's disease, Neuropathic pain, Epilepsy, Multiple sclerosis and Migraine. The intended use for Perampanel was as an add-on therapy to L-dopa in patients with late-stage Parkinson's Disease. However, Perampanel failed in clinical trials to have any effect in Parkinson's Disease. Eisai have consequently decided to terminate further clinical trials for Parkinson's Disease, and its possible future use, but will continue its testing with other medical disorders. For more information go to the News release.

This is the latest of several new approaches to Parkinson's Disease that has been found when properly tested to have no significant effect. Given that Parkinson's Disease is largely due to reduced dopamine, the assessment of Perampanel was lacking a scientific rationale from the outset, because even in theory it was known to have no effect on the formation of dopamine.


10th April 2008 - New research

DEMENTIA AND SURVIVAL IN PARKINSON'S DISEASE                                    

Neurology [2008] 70 (13) : 1017-1022 (Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D.) Complete abstract

The risk of dementia in Parkinson disease is high, with important clinical consequences for people with Parkinson's Disease. However, the absolute risk of dementia and how it affects survival in Parkinson's Disease were not known. Researchers assessed the prevalence of Parkinson's Disease with dementia as people age. Over 60% of people with Parkinson's Disease were eventually found to also have dementia. The cumulative incidence of dementia was
found to steadily increase with age and duration of Parkinson's Disease. So for those that live until 90 years of age the likelihood of dementia increases to 80% to 90%. Women live with Parkinson's Disease longer than men and spend more years with dementia.

At the age of 70, a man with Parkinson's Disease but no dementia has a life expectancy of 8 years, of which 5 years would be expected to be dementia free and 3 years would be expected to be with dementia. Although dementia was found to be common in Parkinson's Disease, and appear almost inevitable in the oldest of sufferers, no comparison was made with the general population to see if people without Parkinson's Disease were almost as likely to develop dementia. Parkinson's Disease is biochemically distinct from dementia. So there is no inevitable reason why they should coincide.


9th April 2008 - New research

TREATING PARKINSON'S DISEASE WITH TROPHIC FACTORS                                                   

Neurotherapeutics [2008] 5 (2) : 270-280 (Peterson AL, Nutt JG.) Complete abstract

Trophic factors are proteins that support and protect cells. A number of them have been reported to act on dopaminergic neurons, the cells whose reduced activity causes Parkinson's Disease. Consequently, it has been claimed that they are potential therapeutic candidates for Parkinson's Disease. They all protect dopaminergic neurons if given prior to, or with, selective neurotoxins. Fewer trophic factors, primarily GDNF (glial-derived neurotrophic factor) and neurturin (NRTN), have been shown to restore function in damaged dopaminergic neurons
after the acute effects of neurotoxins have subsided. However, a major barrier to clinical use has been delivery.

GDNF delivered by intracerebroventricular injection was ineffective, probably because GDNF did not reach the target. Intraputaminal infusion was also ineffective, probably because of limited distribution within the putamen, which is where it was aimed. A clinical trial with gene therapy for NRTN is underway in an attempt to overcome these problems with targeting and distribution. So far, clinical trials have focused on restoration of function. Protection - slowing or halting progression and functional decline - has been suggested to be a more likely effect of trophic agents. Beneficial use for such compounds in patients with Parkinson's Disease remains unproven.


7th April 2008 - New research

TRANSPLANTED CELLS STILL DEVELOP PARKINSON'S DISEASE                                                   

Nature Medicine [2008] Apr 7 [Epub ahead of print] (Jia-Yi Li1, Elisabet Englund, Janice L Holton, Denis Soulet, Peter Hagell, Andrew J Lees, Tammaryn Lashley, Niall P Quinn, Stig Rehncrona, Anders Björklund, Håkan Widner, Tamas Revesz, Olle Lindvall, Patrik Brundin) Complete abstract

Nature Medicine [2008] Apr 7 [Epub ahead of print] (Jeffrey H Kordower, Yaping Chu, Robert A Hauser, Thomas B Freeman, C Warren Olanow) Complete abstract

The dopaminergic neurons are the cells whose deficient activity causes Parkinson's Disease. It had been theorised that new cells transplanted  in to the brain would increase the formation of dopamine because those new cells would
not have developed Parkinson's Disease.

However, two new studies have shown that transplanted cells will cease to function normally, and will still develop changes that are characteristic of Parkinson's Disease. In one study, two subjects who had transplanted dopaminergic neurons developed alpha-synuclein positive Lewy bodies, which are signs of Parkinson's Disease. This shows that implanted cells can develop the same biochemical fault that occurs in Parkinson's Disease. In another study, another individual who'd had new cells, was found to have developed in those cells the Parkinson's Disease symptom of Lewy body–like inclusions that stained positively for alpha-synuclein and ubiquitin. The study confirms that Parkinson's Disease is a biochemical state that can affect any cells - both those that were already there, and those that are placed there.


6th April 2008 - New research

CHOLESTEROL LOWERS THE RISK OF PARKINSON'S DISEASE                                                   

Movement Disorders [2008] Mar 31 [Epub ahead of print] (Huang X, Abbott RD, Petrovitch H, Mailman RB, Ross GW.) Complete abstract

Low density lipoproteins transport cholesterol through the arteries. For more information go to Low density lipoproteins. Low-density lipoprotein cholesterol levels are claimed to be inversely associated with Parkinson's Disease. Basically, it was believed that the the more cholesterol somebody has, the less likely they were to have Parkinson's Disease. To test this hypothesis, the authors studied
over 3,000 men, whose LDL-Cholesterol levels had been measured.

These men were assessed for nearly ten years for the development of Parkinson's Disease. The incidence of Parkinson's Disease increased with decreasing LDL-Cholesterol in a dose-dependent manner. So cholesterol actually made Parkinson's Disease less likely. The association was only significant for men aged 71 to 75 years, but it did make a great difference to chances of getting Parkinson's Disease. This prospective study supports the hypothesis that low LDL-Cholesterol is associated with an increased risk of Parkinson's Disease. The study does not explain why more cholesterol, something usually assumed to be unhealthy, actually lowers the likelihood of Parkinson's Disease.


4th April 2008 - New research

THE EFFECT OF PARKINSON'S DISEASE ON CAREGIVERS                                                
                                                                                                                                                                           European Journal of Physical Rehabilitation Medicine [2008] 44 (2) : 39-45 (Lokk J.)
Complete abstract

The task of managing care for patients with Parkinson's disease often falls upon a family member taking on the role as a caregiver. The aim of this study was to evaluate the strain on caregivers of Parkinson's Disease patients.  The mean age of caregivers was 68, with nearly two thirds being female, probably because there are more men than women with Parkinson's Disease to care for. The general health of caregivers was regarded as satisfactory, independently of how long the person they had been caring for had Parkinson's Disease. However, caregivers still suffered a variety of problems due to being caregivers.

The following problems occurred in caregivers, with the percentage of caregivers that experienced them : disease related stress 61%,  insufficient sleep 31% (often because of the disturbed sleep of the person they were caring for), decreased mood 31%, daily problems with tiredness and sleep disturbance 30%, hypertension 27%, muscle strain headache and fatigue 17%, gastro-intestinal problems 14%. Most of these were unrelated to the duration of the Parkinson's Disease of the person they were caring for. Caregivers found motor dysfunction the most difficult problem to deal with in those they cared for, with 58% of caregivers citing this as the worst problem. More than half of the caregivers experienced little or no understanding of their situation.


2nd April 2008 - New research

                                                                                                                                             Parkinsonism Related Disorders [2008] Mar 26; [Epub ahead of print] (Lee MS, Lam P, Ernst E.) Complete abstract

The after effect of exercise is reduced muscle contraction, which is the same aim as Parkinson's Disease drugs. For this reason, and to maintain mobility, many people supplement their Parkinson's Disease treatment with exercise. It has often been claimed that Tai Chi is a particularly good form of exercise for this purpose. Tai Chi is a traditional Chinese martial art and form of exercise. For more information go to Tai Chi.

The objective of this review was to assess the effectiveness of Tai Chi as a treatment option for Parkinson's Disease. All relevant studies in the medical literature were examined. Of the seven studies included, one randomised clinical trial found Tai Chi to be superior to conventional exercise for Parkinson's Disease, and the prevention of falls. Another trial found no effects of Tai Chi on locomotor ability compared with Qigong. The third failed to show any effects of Tai Chi in Parkinson's Disease. The remaining studies were either non-randomised or uncontrolled clinical trials. In conclusion, the evidence is insufficient to suggest that Tai Chi is effective in Parkinson's Disease.


1st April 2008 - New research


Journal of the Neurological Sciences 2008 Mar 25; [Epub ahead of print] (Havlikova E, van Dijk JP, Rosenberger J, Nagyova I, Middel B, Dubayova T, Gdovinova Z, Groothoff JW.) Complete abstract
                                                                                                                                               Many patients with Parkinson's disease suffer from non-motor symptoms such as sleep disturbances, excessive daytime sleepiness and fatigue. The aim of this research was to find out whether fatigue in Parkinson's Disease is caused by sleepiness and sleep problems, or depression, and how that is related to a person's functional status. Sleepiness did not show significant association with fatigue in any aspect of fatigue.

Neither did the quality of a person's sleep. It was depression that was significantly associated with all aspects of fatigue, the strongest being the relationship with general fatigue, then reduced motivation, then mental fatigue, then physical fatigue, and finally with reduced activity. The worsening of functional status was significantly related most of all to reduced activity, then general fatigue, then physical fatigue, and then mental fatigue. So it is primarily depression that causes fatigue in Parkinson's Disease. Fatigue can in turn worsen symptoms.


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