PARKINSON'S DISEASE NEWS

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15th November 2008 - History

ADOLF HITLER AND PARKINSON'S DISEASE

The Nazi leader, Adolf Hitler, was known to have Parkinson's Disease from 1933 until his suicide in 1945 [reference]. At the end of the Second World War he was largely confined to his bunker in Berlin. In his final days in the bunker, he shuffled around his room, mumbling to himself, repeating the same phrases, sometimes pointing to his hand and saying repeatedly, "Look it is getting better". It's not trembling so much, and I can keep it still". He had trembling hands and stooped shoulders. The stoop may have been due in part to a lack of exercise. He also had tremor in his left leg. The right arm trembled more than the left. With his hand extended and fingers spread he did not tremor. His shaking was related to emotional upsets. When the military situation became far worse his left hand tremor was stronger. At the end he had a stooped back, could barely walk, a shuffling gait, his right leg was dragging, he had head shaking.  His left hand violently trembled on a limply dangling arm. Physically, he had quickly deteriorated and developed the appearance of an old man. The Nazi hierarchy had throughout tried to conceal his Parkinson's Disease by all means. There are two films of Adolf Hitler's last public appearance, one that was shown in which he displayed no symptoms of Parkinson's Disease, and another that was purposefully not shown in which he was displaying the symptoms of Parkinson's Disease.

Hitler was treated by his personal physician, Dr Theo Morrell.  Theo Morell was well known in Germany for his unconventional, holistic and alternative treatments. Dr Morell kept very detailed diaries of his treatment of Hitler's Parkinson's Disease. For more details see the The Secret diaries of Hitler's Doctor  This is the complete book. Hitler was being given 28 different pills a day along with numerous injections every few hours. Dr Morell saw Hitler every day, sometimes 2 or 3 times daily. Field Marshall Gerd von Rundstedt described Hitler as constantly fumbling with Vitamultin tablets or "whatever junk Morell had given him". Hitler was also a vegetarian, drank no alcohol, didn't smoke, and drank decaffeinated coffee. Dr Morell made an attempt at temporarily influencing Hitler's Parkinson's Disease by subcutaneous injections of Harmin (one drop, then one drop, then two drops), and by administering one drop of Homburg 680 (am, midday, evening). On April 22nd, 1945 Hitler dismissed Morell from his bunker in Berlin, saying that he didn't need any more medical help. Dr Morell's methods still continued after he went, because he left behind a lot of pre-prepared medicine.  A week later, Hitler was dead.

12th November 2008 - New research

CEASING DOPAMINERGIC DRUGS IN ADVANCED PARKINSON'S DISEASE

Journal of the American Medical Directors Association [2008] 9 (9) : 670-675 (Tse W, Frisina PG, Halbig TD, Gracies JM, Liang L, Tarshish C, Lesser G, Neufeld R, Koller WC, Libow LS.) Complete abstract

There is a biochemical reaction to dopaminergic drugs, which causes them to have an opposite after effect.  L-dopa causes somebody to produce even less of their own dopamine. Dopamine agonists eventually cause the dopamine receptors to become less sensitive. Researchers determined the effects of dopaminergic medication withdrawal in advanced Parkinson's Disease. Patients were divided between those that continued with L-dopa, and those that ceased the use of L-dopa. Those patients who completely ceased their use of L-dopa actually showed no difference from those that did not. Overall, no significant changes were observed between the control and experimental groups in cognitive, behavioural, and motor functions. Of interest, some of the drug withdrawal patients actually showed modest improvements in cognitive function. The researchers consequently suggest that in patients with advanced Parkinson's Disease and dementia, dopaminergic medication withdrawal may be a feasible way to reduce the use of multiple drugs, and potential medication-related side effects, with a minimal risk of worsening motor deterioration.

9th November 2008 - New research

POWER LINES AFFECT NEUROLOGICAL DISORDERS

American Journal of Epidemiology [2008] Nov 5; [Epub ahead of print] (Huss A, Spoerri A, Egger M, Roosli M; for the Swiss National Cohort Study.) Complete abstract

Residence near power lines has been shown to increase the likelihood of certain neurological disorders. The relationship between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among nearly 5 million people. Overall, the adjusted likelihood of mortality in Alzheimer's Disease in people living within 50m of a 220-380 kV power line was 1.24 times greater compared with persons who lived at a distance of 600m or more. Alzheimer's Disease and dementia tend to increase in likelihood as Parkinson's Disease progresses. The number of years somebody lives near near power lines also increases the risk of mortality in Alzheimer's Disease. People living at least 5 years within 50m of power lines had an increased likelihood of 1.51 times normal, which increases to 1.78 times after 10 years of living near power lines. The likelihood doubled after 15 years of living near power lines. The pattern was similar for senile dementia. However, there was little evidence of increased mortality in Parkinson's Disease.

5th November 2008 - News release

NEW DOSAGES OF STALEVO

One of the major problems in medicine is inappropriate dosages. Either dosages are insufficient to rid symptoms, or more commonly are excessive. Excessive dosages can be tempting because they can completely rid symptoms. However, they often cause a biochemical reaction called "feedback inhibition". Feedback inhibition causes the body to counteract the effect of any drug by reducing the very same function that the drug is attempting to increase. Consequently, excessive dosages can eventually cause the same very same medical problem that it is attempting to treat. Dopamine is produced naturally in the brain. For more information go to the Biochemistry of Parkinson's Disease. Parkinson's Disease drugs greatly interfere with this natural formation of dopamine.

Stalevo consists of L-dopa and Carbidopa (as does Sinemet), and also Entacapone, which prolongs their effect. It is seen by many as a more effective drug than Sinemet. New dosages of Stalevo have been approved for use in the U.S.A.. The approval of Stalevo 75 and 125 tablets (18.75 mg carbidopa, 75 mg levodopa, 200 mg entacapone and 31.25 mg carbidopa, 125 mg levodopa, 200 mg entacapone, respectively) provides physicians with options that may enable more customized approaches to treating people with Parkinson’s Disease. This enables them to avoid dosages that are excessive to the patients needs. These new dosage strengths complement the already existing Stalevo 50, 100, 150 and 200 tablets. For more information go to the Complete article.

The U.S. patents for Stalevo have been challenged. The challenger, Wockhardt, has filed a new drug-marketing application based on this challenge, that would enable them to produce and market a generic version of Stalevo in 12.5, 200 and 50 mg strengths. For more information go to the Complete article.

24th October 2008 - New research

tremor only PARKINSON'S DISEASE

Acta Neurologica Belgica [2008] 108 (2) : 48-52 (Leventoglu A, Baysal AI.) Complete abstract

Although tremor is often considered to be a characteristic symptom of Parkinson's Disease, about 30% of people who have Parkinson's Disease don't have tremor. However, there are some people with Parkinson's Disease whose symptoms are virtually only tremor. Researchers analysed what happened to people whose first symptoms were tremor, in order to see if they eventually developed other symptoms of Parkinson's Disease, such as rigidity and bradykinesia (slowing of movement). Even amongst those people with only tremor there were found to be different types : those with rest tremor, mainly in the upper limbs; those with rest tremor only in a lower limb; and those with only jaw tremor. Some patients with pure Parkinsonian tremor were found to be without bradykinesia or rigidity for a long time. This means that instead of the typical (and false view) of Parkinson's Disease including tremor, rigidity and bradykinesia (slowing of movement), that there were those at one extreme with only tremor, and those at the other extreme who have no tremor at all. There is therefore clearly no characteristic set of symptoms that define Parkinson's Disease.

17th October 2008 - New review

implanted neurons DEVELOP PARKINSON'S DISEASE

Nature Reviews Neuroscience [2008] 9 (10) : 741-745 (Brundin P, Li JY, Holton JL, Lindvall O, Revesz T.) Complete abstract

This review details how new cells put in to the brain to rid Parkinson's Disease develop the signs of Parkinson's Disease themselves. The Neuropathological changes in Parkinson's disease usually progress slowly and spread according to a characteristic pattern. Recent papers have shed light on this progression of pathology by examining the fate of neurons grafted into the brains of patients with Parkinson's Disease. Two of these studies demonstrate that new healthy neurons grafted in to the brains of people with Parkinson's Disease gradually develop the same pathology as the existing neurons. According to these studies, implanted neurons developed biochemical symptoms of Parkinson's Disease after transplantation : alpha-synuclein- and ubiquitin-positive Lewy bodies. It is inevitable that any new cells will eventually function at the same insufficient rate as the existing cells, because their biochemical environment would be identical.

15th October 2008 - New research

vitamin d deficiency in parkinson's disease

Archives of Neurology [2008] 65 (10) : 1348-1352 (Evatt ML, Delong MR, Khazai N, Rosen A, Triche S, Tangpricha V.) Complete abstract

Researchers compared the prevalence of vitamin D deficiency in patients with Parkinson's Disease with age-matched healthy controls and patients with Alzheimer disease. Significantly more patients with Parkinson's Disease (55% of them) had insufficient vitamin D, in comparison to 36% healthy controls, and 41% in people with Alzheimer's Disease. The researchers claim that this data supports a possible role of vitamin D insufficiency in Parkinson's Disease. They suggest that further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in the cause and clinical course of Parkinson's Disease. However, Vitamin D has no role at all in the formation of dopamine, the substance whose deficiency causes Parkinson's Disease. For more information go to the Biochemistry of Parkinson's Disease. Also, in severe cases of Vitamin D deficiency, there is no known relationship with Parkinson's Disease as there would be if Vitamin D deficiency could cause it. The primary role of Vitamin is in the formation and structure of bone. Sunlight is a known source of Vitamin D. The link between Vitamin D and Parkinson's Disease may be due to those people with Parkinson's Disease who have mobility problems being exposed to less sunlight. Although sunlight and certain foods are sources of Vitamin D, they are usually insufficient sources. However, vitamin supplements usually supply 50%-100% of a person's needs.

13th October 2008 - New clinical trial

Nexalin device clinical trial

The Michael J.Fox Foundation is to carry out a clinical trial using the Nexalin Device. For more information go to The Michael J.Fox Foundation. Nexalin Therapy is a technology that uses a mild stimulation of the brain to treat a variety of mood disorders, specifically Anxiety, Depression, and Insomnia. The waveform of Nexalin is administered by placing medical grade conductive pads produced specifically for the Nexalin device on the forehead and behind each ear, which are connected to the Nexalin device with thin cables. The patient is placed in a reclining chair for the duration of a treatment session, which typically lasts for approximately forty minutes. For more information go to Nexalin Advanced Therapy. The disorders usually treated share a similar biochemistry with Parkinson's Disease. The intended effect appears to be like a milder version of DBS (Deep Brain Stimulation) but without using surgery as DBS does. In January 2008, a number of Parkinson's Disease patients carried out their own informal study. For more information go to ParkinsonsRebels.

8th October 2008 - New research

THE EFFECT OF RASAGILINE ON PARKINSON'S DISEASE

Fortschritte der Neurologie Psychiatrie [2008] 76 (10) : 594-599 (Jost WH, Klasser M, Reichmann H.) Complete abstract

Rasagiline (Azilect) is a is a MAO-B inhibitor that is sometimes used for the treatment of Parkinson's Disease on its own, or by people who are taking L-dopa, who are having end of dose fluctuations. This large study gave special attention to the effect of Rasagiline on the patients' quality of life. Different aspects of quality of life were rated by the patients using the self-rating Parkinson's Disease Questionaire (PDQ-39) and the Columbia University Rating Scale (CURS). In addition, patients documented the number of hours spend in the OFF-state. Rasagiline was found to be most used alongside L-dopa (in 82% of people taking it), and then by people taking dopamine agonists (in 66% of cases). The symptom score was reduced by 22% using Rasagiline. The proportion of patients with OFF-periods, which is the main purpose of its use, reduced from 66% to 49%. Time spent in the OFF period was also reduced from an average of 2 hours to 45 minutes. Quality of Life improved by 15%. Rasagiline was found to give better effects than Selegiline in every respect. Besides the side effects that it causes, Rasagiline will eventually lead to an opposite effect due to a biochemical process called "feedback inhibition". This is a means the body uses to counteract anything artifical imposed on it.

3rd October 2008 - New review

PARAQUAT AS A CAUSE OF PARKINSON'S DISEASE

Paraquat is the trade name for N,N'-Dimethyl-4,4'-bipyridinium dichloride, a quaternary ammonium herbicide. Other members of this class include diquat, cyperquat, diethamquat, difenzoquat and morfamquat. The compound is widely used as a quick-acting, non-selective herbicide. It kills green plant tissue on contact and is redistributed within the plant but does not harm mature bark. Paraquat was first produced for commercial purposes in 1961 by ICI (now Zeneca) and is today among the most commonly used herbicides. Pesticides are known to be associated with an increased rate of Parkinson's Disease [1].

Common means : Paraquat is used as a herbicide. There is a greatly increased likelihood of developing symptoms by people involved in horticulture and agriculture [2]. Pesticides are also known to affect well water [3].

Means of toxicity : Paraquat structurally resembles MPTP and its metabolite MPP+. MPTP and MPP+ are neurotoxic chemicals, that induce Parkinson's Disease in exposed humans. Paraquat might therefore might, as do MPTP and MPP+ inhibit tyrosine hydroxylation, which is essential for the formation of dopamine.

Symptoms : Paraquat is known to kill dopaminergic neurons in mice [4, 5], and is associated with the symptoms of Parkinson's Disease in humans [6]. However, it is claimed that Paraquat only potentiates the effect of Maneb - another fungicide [7, 8], and that is has no effect on humans on its own [9].

References : [1] Neurology [1998] 50 (5) : 1346-1350 (J.M.Gorell, C.C.Johnson, B.A.Rybicki, E.L.Peterson, R.J.Richardson); [2] Scandinavian journal of work, environment & health. [2000] 26 (4) : 359-362 (F.Tuchsen, A.A.Jensen); [3] Pesticides in well water : http://www.pueblo.gsa.gov; [4] Antioxidants & redox signaling [2005] 7 (5-6) : 649-653 (D.Bonneh-Barkay, W.J.Langston, D.A.Di Monte); [5] Brain Research [1999] 823 (1-2) : 1-10 (A.I.Brooks, C.A.Chadwick, H.A.Gelbard, D.A.Cory-Slechta, H.J.Federoff); [6] Neurology [1997] 48 (6) : 1583-1588 (H.H.Liou, M.C.Tsai, C.J.Chen, J.S.Jeng, Y.C.Chang, S.Y.Chen, R.C.Chen); [7] Journal of Neuroscience [2000] 20 (24) : 9207-9214 (M.Thiruchelvam, E.K.Richfield, R.B.Baggs, A.W.Tank, D.A.Cory-Slechta); [8] Brain Research [2000] 873 (2) : 225-234 (M.Thiruchelvam, B.J.Brockel, E.K.Richfield, R.B.Baggs, D.A,Cory-Slechta); [9] Klinische Wochenschrift [1988] 66 (22) : 1138-1141 (T. Zilker, F.Fogt, M.Von Clarmann)

26th September 2008 - New research

L-DOPA CO-DRUGS

A new collection of disease-specific stem cell lines have been produced, all of which were developed using the new induced pluripotent stem cell (iPS) technique. The new cell lines were developed from the cells of patients suffering from a range of conditions from Down Syndrome to Parkinson's disease. The cell lines the researchers produced carry the genes or genetic components for 10 different diseases, including Parkinson's Disease. They wanted to  produce a large number of disease models for stem cell research community to accelerate research. They believe that these cells are invaluable tools that will allow researchers to watch the development diseases outside of the patients, and that this will make it possible to find new treatments, and eventually drugs, to slow or even stop the course of a number of diseases, including Parkinson's Disease. "The cell lines available from the iPS Core will allow stem cell researchers around the world to explore possible gene therapies for some conditions, and will aid in the development of drugs for others," Daley said.
                                                                                                                                                                                           The biochemistry of the dopaminergic neurons (the cells involved in Parkinson's Disease) is already well known. Therefore, there is limited potential benefit from further examination of these cells. Most medical researchers are not aware of what is already known of the biochemistry of Parkinson's Disease.  Consequently, the vast majority of research being carried out is fundamentally flawed because it is based on false assumptions and scientific ignorance.

4th August 2008 - News report

a ten year old with parkinson's disease

At the age of ten, Andrew Carnegie who is now 12 years old, started developing Parkinson's Disease symptoms. He suffered from stiffness and cramps in the muscles. He lost his balance easily, and fell frequently. Numerous attempts at obtaining a diagnosis failed. He was not readily diagnosed with Parkinson's Disease because he was so much younger than the false and stereotypical view of Parkinson's Disease only occurring in old people. After he was eventually diagnosed, regular Sinemet readily rid his symptoms. For more information go to the Complete article. There have previously been children even younger than 10 years old who have had Parkinson's Disease. The youngest known case of Parkinson's Disease was described in 1875 by Henri Huchard who had a patient that had all of the symptoms of Parkinson's Disease who was only three years old. A ten year old American girl experienced her first symptom at only two years old. It is uncommon for people under the age of thirty to develop Parkinson's Disease, which usually occurs when people are significantly older. However, Parkinson's Disease does not become progressively more likely with age, because amongst the very oldest of people (those between 110 and 119 years old) Parkinson's Disease is hardly known.

3rd August 2008 - New forum

the irish parkinson's disease forum

The Irish Parkinson's Disease Forum has been set up for Irish people with an interest in Parkinson's Disease to discuss Parkinson's Disease, and the issues and events in Ireland concerning it. This includes the work and activities of the two Irish Parkinson's Disease organisations : The Parkinson's Association of Ireland, and PALS support group, which is primarily for younger people. The Irish Parkinson's Disease Forum is at present the only Parkinson's Disease Forum for Irish people. The forum is new, independent and open to anyone to become a member.  For their web site, double click on The Irish Parkinson's Disease Forum

2nd August 2008 - New research

an autoimmune hypothesis of parkinson's disease

Cell Transplantation [2008] 17 (4) : 363-372 (Monahan AJ, Warren M, Carvey PM.) Complete abstract

Studies have demonstrated that a number of substances readily cause toxic damage to the cells that produce dopamine. However, neuroprotective strategies aimed at dealing with this toxicity have been largely ineffective in treating Parkinson's Disease. The researchers suggest that this may be because the progression of Parkinson's Disease is a consequence of an additional mechanism. Whilst they considered this, they discovered that animals whose dopamine producing cells  were exposed to the neurotoxins exhibited blood-brain barrier (BBB) dysfunction. The blood brain barrier is what usually protects the brain from a number of damaging substances. If the blood-brain barrier (BBB) in people with Parkinson's Disease is disrupted, immune cells could enter brain and produce a self-perpetuating (progressive) degenerative process. In this review, the authors propose that peripheral immunity contributes to the degenerative process of Parkinson's Disease and may be responsible for the progressive nature of the disease. In order to understand this hypothesis, the authors claim that the reader must question the conventional wisdom that the blood-brain barrier  is intact in Parkinson's Disease.

In support of their theory, the leading researcher concerning the blood brain barrier in Parkinson's Disease claimed several years ago that the blood brain barrier was dysfunctional in Parkinson's Disease [1] [2]. However, these studies were not age controlled, which is a considerable failing, because people with Parkinson's Disease tend to be older. His subsequent studies effectively nullified the basis for the blood brain barrier theory being dysfunctional in Parkinson's Disease. He first found that the blood brain barrier tended towards being dysfunctional in older people anyway, regardless of whether or not they had Parkinson's Disease [3]. He also found that when people developed Parkinson's Disease they did not have a dysfunctional blood brain barrier [4]. The blood brain barrier being no more dysfunctional in Parkinson's Disease than in anyone else of a similar age leaves the autoimmune theory of Parkinson's Disease without the basis it requires.

31st July 2008 - News release

michael j.fox foundation funds "RAPID RESPONSE AWARDS"

The Michael J. Fox Foundation is funding what they describe as "Cutting-edge Approaches to Parkinson's Disease" under Rapid Response Innovation Awards 2008. Among the projects funded are : (1) To determine whether a gene silencing technique can be effective in reducing alpha-synuclein, a protein whose aggregation, or clumping, in the brain is sometimes found in Parkinson’s Disease. (2) Using newly induced pluripotent stem cell technology to shed greater light on the Parkinson’s-implicated genes parkin and LRRK2. (3) To better understand epidemiological findings that have consistently shown smoking may protect against Parkinson's Disease. Researchers hope to elucidate the mechanisms by which nicotine may protect dopamine neurons through development of a screening test for small molecules that could increase nicotine receptor expression in the brain. (4) To find better treatments for the digestive problems that affect Parkinson’s patients’ quality of life, as well as test the Braak hypothesis, which claims that Parkinson’s disease progresses through the body to the brain in a series of stages starting in the gastrointestinal system. For more information go to The Michael J.Fox Foundation.

These latest projects, are lacking in a sound scientific rationale : (1) Alpha synuclein cannot logically be claimed to cause Parkinson's Disease because alpha synuclein occurs in people without any trace of Parkinson's Disease. (2) The Parkin and LRRK2 genes have merely inclined a small proportion of people towards Parkinson's Disease. They certainly aren't inevitable causes of Parkinson's Disease, even in the small proportion of people that are affected by them. (3) Nicotine receptors have never been shown to be responsible for Parkinson's Disease. Drugs already known to affect the nicotine receptors have never rid anyone of Parkinson's Disease. (4) The Braak hypothesis that Parkinson's Disease is caused by the gastrointestinal system is equally unsound. L-dopa rids Parkinson's symptoms despite not having any beneficial effect on the gastro-intestinal system. There are dozens of cell types in the brain that would be affected by Braak's theory. Yet Parkinson's Disease can occur without somebody simultaneously suffering from every other neurological disorder.

28th July 2008 - New review

parkinson's disease SYMPTOM QUESTIONNAIRES

Despite the increasing use of scanning methods to diagnose Parkinson's Disease, symptom questionnaires remain the most common method of assessing symptoms.  The most commonly used symptom questionnaire is the Unified Parkinson Disease Rating Scale (UPDRS). The UPDRS was developed to address the need for a comprehensive Parkinson's Disease measurement tool. It encompasses earlier rating scales : Hoehn and Yahr staging scale, and the modified Schwab and England activities of daily living scale. In monotherapy, a “Total UPDRS” score is the combined sum of parts I, II, and III: 0 (not affected) to 176 (most severely affected). In adjunct therapy, part IV is included. Part IV contains 11 questions and the scale can range from 0 to 23. For an understanding of the UPDRS go to UPDRS.

The Hoen and Yahr characterises patients according to a scale of five stages of severity, from Stage 1, which is mild, to Stage 5, which is incapacitated. For the questionnaire go to the Hoehn and Yahr scale. The Schwab and England Activities of Daily Living assesses patients in terms of their degree of independence concerning their functions - with a range a percentages from 100% to 0%. Rating can be assigned by the rater or the patient. For the questionnaire go to the Schwab and England.

The PDQ39 assesses the quality of life. The PDQ-39 is the most widely used Parkinson's Disease specific measure of health status. It contains thirty nine questions, covering eight aspects of quality of life. Scores on the PDQ range from 0 to 100, with higher scores reflecting greater problems. For the questionnaire go to PDQ 39. The PDQL is a self administered measure that contains 37 items contained in four sub-scales : parkinsonian symptoms, systemic symptoms, social functioning. An overall scale can be derived, with a higher score indicating better perceived quality of life. For the questionnaire go to the PDQL. For more information on the diagnosis of Parkinson's Disease, go to Diagnosis of Parkinson's Disease.

26th July 2008 - New research

HALLUCINATIONS IN parkinson's disease

Practical Neurology [2008] 8 (4) : 238-241 (Poewe W.) Complete abstract

Visual hallucinations occur in up to 40% of people with Parkinson's disease. However, hallucinations are not actually due to Parkinson's Disease. Age and cognitive decline are the most important intrinsic risk factors, but hallucinations are often triggered by conditions such as infection and dehydration. The single most important trigger, however, is the use of  CNS drugs, especially drugs for Parkinson's Disease. While hallucinations and psychosis can be triggered by amantadine and anticholinergics, they are more commonly experienced after changes in dopaminergic drugs. Dopamine agonists have the greater potential to induce hallucinations compared with L-dopa. Attempting to reduce Parkinson's Disease drugs is an important part in the management of these symptoms, but atypical neuroleptics like clozapine or quetiapine are often also used. Visual hallucinations in Parkinson's disease patients with dementia can also be improved by treatment with the cholinesterase inhibitor rivastigmine.

22nd July 2008 - New research

blood mechanisms claimed to cause parkinson's disease

Many people with Parkinson's Disease have elevated levels of a protein called alpha-synuclein in their brains. As alpha-synuclein accumulates, the resulting toxicity is claimed to cause damage to the cells that produce dopamine. Researchers were surprised to notice that there were also large amounts of alpha-synuclein in the blood.  The researchers discovered that the activity of genes that control the formation of hemoglobin, which is what enables blood to carry oxygen, precisely matched the activity of the alpha-synuclein gene, suggesting a common switch controlling both the formation of blood, and the damage that occurs in Parkinson's Disease. The  protein called GATA-1, which turns on the genes in the blood, was also a major switch for producing alpha-synuclein. They also demonstrated that a related protein, GATA-2, was produced in brain cells that were vulnerable to Parkinson's Disease. The researchers claim that being able to reduce the formation of alpha-synuclein by 40%  may be enough to treat some forms of Parkinson's disease. For more information go to the Complete article.

The main weakness in the claim that alpha-synuclein causes Parkinson's Disease and that its reduction will rid it, is that a lot of people with Parkinson's Disease do not have large amounts of alpha-synuclein. There is no evidence that alpha-synuclein actually causes Parkinson's Disease, only that it can be associated with it. Alpha-synuclein is associated with a variety of medical disorders that are not Parkinson's Disease. Parkinson's Disease does not usually coincide with these medical disorders as it would if alpha-synuclein was the cause of Parkinson's Disease. Alpha-synuclein produced in the blood is unable to pass in to the brain in order to cause Parkinson's Disease anyway.

19th July 2008 - News release

michael j.fox foundation funds nine new approaches

The Michael J. Fox Foundation for Parkinson’s Research has announced approximately $2.4 million funding for nine research projects. This annual program provides resources to help push potential Parkinson's Disease drug targets toward clinical trials. Target validation is a phase of drug development in which researchers work to determine whether a molecule or mechanism of interest is a true drug target.

The nine projects are (1) CaMKII as a Therapeutic Target in Parkinson's Disease, (2) Evaluation of the Striatum-enriched Genes CalDAG-GEF1 and CalDAG-GEF2 as Targets for the Treatment and Prevention of L-DOPA Induced Dyskinesia, (3) Hsp90 as a Target for Neuroprotective Agents in Parkinson's Disease, (4) NBD Peptides in a Non-Human Primate Model of Parkinson's Disease, (5) Mu Opioid Receptors as a Drug Target for Treating Motor Fluctuations in PD, (6) Dopaminergic Neuroprotection by Regulator of G-protein Signaling 10 (RGS10), (7) Validation of the NR2D Subunit of the NMDA Receptor as a Therapeutic Target for Parkinson's Disease, (8) NR2B as a Therapeutic Target in Parkinson's Disease, (9) SIRT1 Activators as Therapy for Parkinson's Disease. For more information go to The Michael J.Fox Foundation.

These projects all aim at finding targets for new drugs. However, none of them, even in theory, address the known biochemical fault in Parkinson's Disease, which is insufficient formation of dopamine. All of the projects are biochemically far removed from the possibility of increasing dopamine formation, and are consequently without any scientific rationale that would justify their use. The Michael J.Fox Foundation web site claims "We don't just fund research. We fund results." However, none of the projects previously funded by the Foundation have ever resulted in anyone being rid of Parkinson's Disease.

16th July 2008 - New research

suicide in parkinson's disease

Movement Disorders [2008] Jul 10; [Epub ahead of print] (Nazem S, Siderowf AD, Duda JE, Brown GK, Ten Have T, Stern MB, Weintraub D.) Complete abstract

In Parkinson's disease, there is a high prevalence of depression. This is because dopamine, whose deficiency normally causes the muscular symptoms of Parkinson's Disease, also affects the emotions. Many people with Parkinson's Disease consequently effectively become biochemically depressed. Depression increases the likelihood of suicide and thoughts of death. However, little was known of their prevalence in Parkinson's Disease. People with Parkinson's Disease were assessed using the Paykel scale.  Respondents answer each item either "yes" or "no" to the following questions. The items can assess suicidality during the past week, month, year or lifetime. More relevant to somebody with Parkinson's Disease is for the answers to concern recent months :

1. Have you ever felt that life was not worth living ?
2. Have you ever wished you were dead? for instance, that you could go to sleep and not wake up ?
3. Have you ever thought of taking your life, even if you would not really do it ?
4. Have you ever reached the point where you seriously considered taking your life or perhaps made plans how you would go about doing it?
5. Have you ever made an attempt to take your life ?

Extensive psychiatric, neuropsychological, and neurological assessments were also carried out. Thoughts of death occurred in 28% of patients. Thoughts of suicide occurred in 11% of patients. Thoughts of either had occurred in 30% of patients. Of all those assessed, 4% had attempted suicide during their lifetime. Depression was far more common than normal. Even more common was impulse control disorder, but this was probably due to Parkinson's Disease drugs, especially dopamine agonists. Psychosis was also far more common in Parkinson's Disease, but this was also probably due to Parkinson's Disease drugs, especially L-dopa.

13th July 2008 - New research

essential tremor developing in to parkinson's disease

Movement Disorders [2008] Jul 10; [Epub ahead of print] (Minen MT, Louis ED.) Complete abstract

There is a blurred distinction between Essential Tremor and Parkinson's Disease. There are people with Essential Tremor who have a degree of muscle rigidity, which is more characteristic of Parkinson's Disease. Most people with Parkinson's Disease have tremor, but around 30% don't have tremor at all. Patients with essential tremor can develop Parkinson's Disease. However, few studies have examined the clinical features of this combination syndrome. Patients with ET-PD were compared to those with Parkinson's Disease and others with only Essential Tremor. the time it took to go from the onset of Essential Tremor to Parkinson's Disease was brief - less than five years in nearly 40% of people, but in around 30% of people, Essential Tremor took over 20 years before developing in to Parkinson's Disease. The gender distribution of ET-PD was identical to the male dominance seen in Parkinson's Disease (67.9% male), making it appear to be the same illness. This differed from the gender distribution in Essential Tremor, in which there are roughly equal numbers of men and women. The initial cardinal symptom of people who went from Essential Tremor to Parkinson's Disease was rest tremor in 100% of patients. In ET-PD, the side of greatest initial Essential Tremor severity usually matched that of the greatest Parkinson's Disease severity. So the co-occurrence of the two diagnoses in the same patient may be mechanistically related.

10th July 2008 - New review

It is widely claimed that Parkinson's Disease is primarily due to a lack of dopamine, and L-dopa, which forms it. However, dopamine on its own does nothing at all. Dopamine has to stimulate the dopamine receptors before it has any effect. Dopamine receptors are proteins, which means that they are a long chain of amino acids - just like a pearl necklace is a long chain of pearls. There are five types of dopamine receptor : D1, D2, D3, D4, D5. Each of them are different sizes, as they have a different number of amino acids. D1 has 446. D2 has short and long versions, with the short version being 414 long, and the long version being 443 long. D3 is 400 amino acids long. D4 is usually 387 amino acids long. However, there are a large number of genetic variants of D4, especially amongst Americans. Each of these variants is less functional than the main form of D4, and so may constitute one of the causes of Parkinson's Disease. D5 is 477 amino acids long. The dopamine receptors do not all function in the same way either. The receptors D2, D3 and D4 inhibit the excessive muscle contraction seen in Parkinson's Disease. However, the receptors D1 and D5 are stimulatory, and so increase muscle contraction. Dopamine (and L-dopa, which makes it) reduce the primary symptoms of Parkinson's Disease, which is excessive muscle contraction because the combined effect of D2, D3 and D4 is more powerful than the combined stimulatory effect of D1 and D5.

Dopamine agonists make use of the different functions of the dopamine receptors by primarily stimulating those dopamine receptors that reduce excessive muscle contraction - usually D2 or D3. For example, Mirapex primarily stimulates D3. Parlodel primarily stimulates D2. Whilst Neupro stimulates three dopamine receptors D1, D2, D3. The problem with taking dopamine agonists is that this can disproportionately stimulate certain dopamine receptors rather than others - often giving rise to compulsive behaviours, especially with those that stimulate D3. Continuous use of dopamine agonists also makes the  dopamine receptors progressively less sensitive. Dopamine agonists consequently have progressively less effect, and can also cause naturally produced dopamine to be less effective. In the long term this can make Parkinson's Disease progressively worse. 

5th July 2008 - New research

CALCIUM channel BLOCKERS - A CAUSE OF PARKINSON'S DISEASE

Parkinsonism Related Disorders [1998] 4 (4) : 211-214 (Garcia-Ruiz PJ, Javier Jimenez-Jimenez F, Garcia de Yebenes J.) Complete abstract

Calcium channel blockers are drugs that are widely used to reduce high blood pressure. For more information go to Calcium channel blockers. The symptoms of Parkinson's Disease are a frequent side effect of some calcium channel blockers (CCB). CCB-induced Parkinsonism usually improves spontaneously after discontinuation of the offending drug, but many patients still exhibit persistent symptoms after their withdrawal. It is not known whether Parkinsonism caused by Calcium channel blockers represents sub-clinical Parkinson's disease unmasked by drugs. Researchers studied the development of patients with CCB-induced Parkinsonism, and compared their clinical characteristics with those people with idiopathic Parkinson's Disease. Most patients with CCB-induced Parkinsonism improved spontaneously. Two years after Calcium channel blocker withdrawal, only 14% exhibited akinetic rigid syndrome. However,  92% of them still had tremor. Those people whose Parkinson's Disease symptoms were caused by Calcium channel blockers differed from other people with Parkinson's Disease  in: age at onset (averaging 70 years old rather than 59 years old), presenting symptom (tremor at first evaluation being more common), and a far more common history of arterial hypertension.

4th July 2008 - News release

spheramine (retinal cell therapy) fails clinical trials 

It had been claimed that a cell therapy using retinal pigment epithelial (RPE) cells, called Spheramine, could improve the symptoms of people with Parkinson’s disease. 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. Titan Pharmaceuticals, have announced that Spheramine did not meet the Phase IIb clinical study’s primary or secondary endpoints. There was no significant difference in effect detected between Spheramine and sham surgery. The Phase IIb trial was designed to explore the safety, tolerability and efficacy of Spheramine.  For the statement go to Titan Pharmaceuticals.  It was pointed out on the Viartis web site, over two months before the clinical trial results were known, that Spheramine did not account for the insufficient dopamine formation that is known to cause Parkinson's Disease.

3rd July 2008 - New research

THYROID FUNCTION IN PARKINSON'S DISEASE

Parkinsonism Related Disorders [1999] 5 (1-2) : 49-53 (Bonuccelli U, D'Avino C, Caraccio N, Del Guerra P, Casolaro A, Pavese N, Del Dotto P, Monzani F.) Complete abstract

Thyroid disease is the endocrine dysfunction most frequently reported in association with idiopathic Parkinson's Disease. The aim of this study was to assess thyroid function in Parkinson's Disease, and to verify the effect of long term L-dopa or dopaminergic therapy on thyroid function. Thyroid dysfunction was observed in over than 10% of people with Parkinson's Disease. No significant difference in the prevalence of thyroid autoimmunity and dysfunction was found between people with Parkinson's Disease and those with other nerological disorders. Treatment with L-dopa and other dopaminergic drugs did not affect thyroid function. The severity of Parkinson's Disease did not affect thyroid function either. L-dopa and the thyroid hormones are made from L-tyrosine - a nutrient normally consumed in the diet. Therefore, somebody who has both Parkinson's Disease and Hypothyroidism may be suffering, at least partially, from L-tyrosine deficiency, a problem that can be readily resolved using an L-tyrosine supplement.

1st July 2008 - New web site

Hacia adelante - SPANISH LANGUAGE WEB SITE FOR PARKINSON'S DISEASE

Hacia adelante is a new Spanish language web site for Parkinson's Disease. For the web site go to : Hacia adelante. “Hacia adelante” provides useful information for patients and caregivers from diagnosis through disease progression, including information on managing Parkinson's Disease , treatment options, medical worksheet templates, and resource links. Teva created the Spanish-language resource guide as part of its commitment to providing helpful resources for all people affected by Parkinson's Disease. “Hacia adelante” is available to anyone through their neurologist or by simply visiting www.parkinsonshealth.com under the "Take Control" section. The free resource is available for viewing or download in both Spanish and English.

28th June 2008 - New research

ONE OF THE WORLD'S LOWEST PREVALENCES OF PARKINSON'S DISEASE

Movement Disorders [2008] Jun 25; [Epub ahead of print] (Dotchin C, Msuya O, Kissima J, Massawe J, Mhina A, Moshy A, Aris E, Jusabani A, Whiting D, Masuki G, Walker R.) Complete abstract

The prevalence of Parkinson's Disease varies worldwide from 7 to 407 people per 100,000. For more information go to Prevalence of Parkinson's Disease. The prevalence of Parkinson's Disease appears to be low in sub-Saharan Africa, but little data exists. So the authors conducted a study of the prevalence of Parkinson's Disease in rural Tanzania. Crude prevalence rates were found to be very low : 30/100,000 (for men), 11/100,000 (for women) and 20/100,000 (overall). This makes Tanzanian women, the second least likely group of people in the world to develop Parkinson's Disease. This is despite rural Tanzania having very low levels of healthcare. It is in stark contrast to the U.S.A., where, despite extensive healthcare, people are 30 times more likely to develop Parkinson's Disease. Tanzanian women also have the world's lowest ratio of women to men having Parkinson's Disease, with the women being nearly a third less likely to develop Parkinson's Disease than men. No explanation is given for such low prevalence rates of Parkinson's Disease amongst Tanzanian women.

26th June 2008 - New research

THE PREVALENCE OF PATHOLOGICAL GAMBLING IN PARKINSON'S DISEASE

Journal of Gambling Studies 2008 Jun 17; [Epub ahead of print] (Crockford D, Quickfall J, Currie S, Furtado S, Suchowersky O, El-Guebaly N.) Complete abstract

Pathological gambling has often been identified in people with Parkinson's Disease treated with dopamine agonists. When somebody takes dopamine agonists such as Ropinirole (Requip) and Pramipexole (Mirapex), they disproportionately stimulate the D3 dopamine receptor, far more than L-dopa does. This causes arousal in the limbic system, which is where the D3 dopamine receptor is primarily located. Given that the limbic system is connected with the pleasure centre,  the use of certain dopamine agonists can especially lead to compulsions such as gambling. This study was undertaken to establish the prevalence of pathological gambling in Parkinson's Disease. The prevalence was found to be nearly 10% of people with Parkinson's Disease. This meant that pathological gambling was more than 5 times more likely than in people that didn't have Parkinson's Disease. The increased prevalence of pathological gambling in the Parkinson's Disease group was related to dopamine agonist use and also younger age. Most people suffering from pathological gambling reported that their gambling increased after diagnosis and starting treatment.

25th June 2008 - New research

DYSKINESIA IS RELATED TO WEIGHT

European Journal of Neurology [2008] 15 (5) : 493-496 (Sharma JC, Ross IN, Rascol O, Brooks D.) Complete abstract

L-dopa dose per kilogram body weight is reported to be a significant factor for dyskinesia in Parkinson's disease. This study investigated this hypothesis. Analysis of L-dopa therapy patients revealed that people with dyskinesia had received significantly higher L-dopa dose, and also had a higher L-dopa dose per kilogram body weight. The most significant factor was the higher L-dopa dose per kilogram body weight. Younger age was the factor that was the second most related to dyskinesia. Gender, absolute L-dopa dose, weight, disease duration, and initial motor Unified Parkinson's disease rating score were not significant. Higher L-dopa dose per kilogram body weight is an independently significant factor for developing dyskinesia. This relationship should be considered as an important factor in the treatment of Parkinson's Disease when aiming to prevent and manage dyskinesia, because those of a lower weight will be far more prone to dyskinesia.

24th June 2008 - New research

CHRONIC PAIN IN PARKINSON'S DISEASE

Mvement Disorders [2008] Jun 10; [Epub ahead of print] (Negre-Pages L, Regragui W, Bouhassira D, Grandjean H, Rascol O) Complete abstract

Pain a frequent, but poorly studied symptom of Parkinson's Disease. This survey aimed to assess the prevalence of chronic pain in Parkinson's Disease, to describe Parkinson's Disease patients with chronic pain, and to record analgesic consumption. 62% of people with Parkinson's Disease were found to suffer from chronic pain. 26% of people with Parkinson's Disease had pain unrelated to Parkinson's Disease ("non-PD-pain", caused mainly by osteoarthritis), while 39% had chronic pain related to Parkinson's Disease ("PD-pain"). In this last group, Parkinson's Disease was the sole cause of pain in the majority, whilst the others suffered from indirectly aggravated pain of another origin, which was mainly osteoarthritis. Parkinsonian patients with "PD-pain" were younger at Parkinson's Disease onset, had more motor complications, more severe depressive symptoms than those without pain or with "non-PD pain." "PD-pain" was more intense, but was less frequently reported to doctors, and was associated with less frequent analgesic consumption than "non-PD-pain." Pain was twice more frequent in Parkinson's Disease patients than in patients without Parkinson's Disease. Chronic pain is frequent but underreported in Parkinson's Disease.

15th June 2008 - New book

PARKINSON'S DISEASE AND MOVEMENT DISORDERS

TN Mehrotra

A concise, practical overview of Parkinson's Disease and other movement disorders and their management. It lays out disease epidemiology and pathology, symptoms and signs, features, approaches, fluctation function, pharmacokinetic strategies, and a detailed description of the disease through subjective treatment at various levels. Includes the latest information on the diagnosis and treatment of Parkinson's Disease. Focuses on the long-term care of patients suffering from movement disorders. Begins with a historical perspective on the evolution of treatment for movement disorders. Discusses special issues of the disease such as sleep, depression and dementia, and young onset.