Another resarch on the importance of Glutathione ...
I take NAC which is supposed to be a Glutathione precurser ... any body else is taking it???
http://www.associatedcontent.com/art...arkinsons.html

Lack of Glutathione Linked to Parkinson's Disease
By Rafael_B
Published Dec 20, 2007

According to a new study, published in the most recent issue of the prestigious Journal of Neuroscience, researchers have shown (in animal models) that the lack of glutathione is linked to the development of the Parkison's disease. The study was led by Julie Andersen, PhD., from the Buck Institute for Age Research, Novato, California

The Parkison's disease is a neurodegenerative disorder. Common symptoms are: tremor, slowness of movement and rigidity. No cure is available today for the Parkison's disease. Glutathione is recognized as a potent detoxifying antioxidant that helps the body repair damage from stress, pollution, infection and damage.

Scientists have shown in this study that mice exhausting their levels of glutathione in dopamine-producing neurons developed nerve damage and symptoms that mimic the Parkinson's disease (PD) in humans. Dopamine is a neurotransmitter involved in a myriad in nerve functions.

In this study a special kind of mice was bred. These genetically engineered mice cold are induced (chemically) to develop a depletion of glutathione in neurons as adults and in different stages of their adulthood. When the glutathione depletion was induced in young adults no Parkinsonian-like nerve damage and symptoms occurred. On the contrary if the induction was done in late middle age mice developed loss of neurons specifically related to Parkison's disease.

Another interesting effect was seen in this study. Loss of glutathione in neurons may also have a strong effect of energy production. Energy, at the cellular lever is produced in a sub cellular structure known as mitochondria. Mitochondria are true "power plants" within the cell. Lack of glutathione may have an effect on an enzymatic complex of the mitochondria known as mitochondrial complex I.

Glutathione is available to be taken as a dietary supplement. However, the antioxidant glutathione cannot pass the blood-brain barrier to reach the glutathione starving neurons. So no effect can be seen in Parkinson patients taking glutathione orally.

1: Biofactors. 1997;6(3):321-38.

Lipoic acid increases de novo synthesis of cellular glutathione by improving
cystine utilization.

Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H, Tritschler HJ, Flohé L,
Packer L.

Department of Molecular and Cell Biology, University of California, Berkeley
94720-3200, USA.

Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a
therapeutic agent, and is reported to have beneficial effects in disorders
associated with oxidative stress, but its mechanism of action remains unclear. We
present evidence that lipoic acid induces a substantial increase in cellular
reduced glutathione in cultured human Jurkat T cells human erythrocytes, C6 glial
cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect
depends on metabolic reduction of lipoic acid to dihydrolipoic acid.
Dihydrolipoic acid is released into the culture medium where it reduces cystine.
Cysteine thus formed is readily taken up by the neutral amino acid transport
system and utilized for glutathione synthesis. By this mechanism lipoic acid
enables cystine to bypass the xc- transport system, which is weakly expressed in
lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key
enzyme of glutathione synthesis, gamma-glutamylcysteine synthetase, which is
regulated by uptake-limited cysteine supply, to work at optimum conditions. Flow
cytometric analysis of freshly prepared human peripheral blood lymphocytes, using
monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly
to normalize a subpopulation of cells severely compromised in thiol status rather
than to increase thiol content beyond physiological levels. Hence lipoic acid may
have clinical relevance in restoration of severely glutathione deficient cells.

PMID: 9288403 [PubMed - indexed for MEDLINE]

I was taking 200 mg per day of N-acetyl cysteine until a few months ago. The vitamin/supplement mix I take now (Vitalizer Gold by Shaklee) contains 50 mg of N-acetyl cysteine. I was also taking acetyl carnitine and alpha lipoic acid but am not currently doing so.

Thanks. I take 600mg N-acetyl cysteine and 300mg alpha lipoic acid daily. There is a lot of stuff on the internet on their benifits to PD. But ofcourse the PD doctors never recognise this and we are left to our own judgement. That is why this forum is really valuable.

Any comment on the following?
http://www.medicalnewstoday.com/articles/88119.php

Society For Neuroscience Selects Boston University Medical Center Researcher's Abstract
Main Category: Neurology / Neuroscience News
Article Date: 08 Nov 2007 - 2:00 PST
David Farb, PhD, recently had an abstract selected that was highlighted by the Society for Neuroscience (SFN). The abstract details how antioxidants influence dopamine release from striatal synaptosomes. It was presented at SFN's 37th annual meeting November 7th in San Diego, California.

Farb is the professor and chairman of the Department of Pharmacology & Experimental Therapeutics at Boston University School of Medicine. He is also the director of the Biomolecular Pharmacology Training Program, the interdepartmental program in biomedical neuroscience, and heads the Laboratory of Molecular Neurobiology.

Farb's abstract details the relationship between antioxidants and dopamine. Antioxidants can protect the central nervous system from oxidative damage. The level of oxidation and reduction of molecules reflects conditions within the nervous tissue. Increased levels of oxidative damage are believed to be involved in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and stroke.

In the brain, neurons communicate with each other via synaptic connections in which signals are transmitted by the release of chemical neurotransmitters from presynaptic axon terminals. Farb and fellow BUSM researchers examined the release of a specific neurotransmitter, dopamine, from isolated pre-synaptic axon terminals.

Researchers sought to determine whether the presence of antioxidant compounds could influence spontaneous dopamine release from synaptosomes. They concluded that the release of dopamine could be influenced by numerous factors, including input from other neurotransmitters as well as the reducing/oxidizing state of the cell. Inclusion of the water soluble, sulfhydryl containing antioxidant glutathione, or the glutathione precursor NAC lowered spontaneous dopamine release by 85 percent. The antioxidant vitamin E had no effect on dopamine release.

"Not all antioxidants are equivalent," said Farb. "Our results suggest that the ability of NAC or glutathione at therapeutic doses to rapidly and reversibly stabilize the release of dopamine raises the possibility that such antioxidants may have significant potential for the treatment of oxidative damage in neurodegenerative diseases."

Farb chairs the Executive Committee for the Medical Sciences Training Program and is a member of the Bioinformatics Program. He also served as neurosciences consultant for WGBH-Boston PBS affiliate on the NOVA episode, Mirror Neurons and, as a member of the Drug Development Work Group of Mass Insight. He also co-authored the Massachusetts Technology Road Map for Drug Discovery.

Farb has served as a consultant to large and small pharmaceutical companies, intellectual property law and portfolio investment firms. He was a member of the founding Scientific Advisory Boards of CoCensys and DOV Pharmaceuticals and the Scientific Founder of Scion Pharmaceuticals (acquired by Wyeth), which commercialized his patents on high throughput electrophysiology and small molecule modulators of amino acid receptors. Farb currently serves on the SAB of DOV Pharmaceuticals and Helicon Therapeutics (pending). He holds nine issued U.S. patents and one patent issued in Australia.

Farb's current research is directed toward understanding the mechanisms of action of abused substances and steroid hormones and their interactions with excitatory and inhibitory amino acid receptors in the central nervous system. The research focuses on the mechanism of action and discovery of neuromodulators as therapeutic agents and on the structure, function, and cellular dynamics of ion channels and receptors in the brain and spinal cord. Recently, Farb's laboratory demonstrated that pregnanolone hemisuccinate inhibits reinstatement of cocaine seeking behavior and this compound has been acquired by NIDA for preclinical development in its Medications Development Program.

...is that Farb sure is cozy with Big Pharma. I just wonder if he would tell us if NAC (which is non-patentable) was just as good as anything that he might hope to find that could patentable.

The second thought that somebody owes Dr. Perlmutter an apology for the years they laughed at his work with glutathione.

And third is a mental note to pick up some NAC.

Linus Pauling was a Nobel winner...

http://lpi.oregonstate.edu/infocente...gical_activity

Protein-Bound Alpha-Lipoic Acid

Enzyme Cofactor
R-LA is an essential cofactor for several mitochondrial enzyme complexes that catalyze critical reactions related to energy production and the catabolism (breakdown) of alpha-keto acids and amino acids (17). In each case, R-LA is covalently bound to a specific lysine residue in one of the proteins in the enzyme complex. The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-coenzyme A (CoA), an important substrate for energy production via the citric acid cycle. The alpha-ketoglutarate dehydrogenase complex catalyzes the conversion of alpha-ketoglutarate to succinyl CoA, another important citric acid cycle intermediate. The activity of the branched-chain ketoacid dehydrogenase complex results in the catabolism of the branched-chain amino acids, leucine, isoleucine and valine (18). The glycine cleavage system is a multi-enzyme complex that catalyzes the oxidation of glycine to form 5,10 methylene tetrahydrofolate, an important cofactor in nucleic acid synthesis (19).

Free Alpha-Lipoic Acid

When considering the biological activities of supplemental free LA, it is important to keep in mind the limited and transient nature of the increases in plasma and tissue LA (see Metabolism and Bioavailability above) (3).

Antioxidant Activities

Scavenging Reactive Oxygen and Nitrogen Species: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive compounds with the potential to damage DNA, proteins and lipids (fats) in cell membranes. Both LA and DHLA can directly scavenge (neutralize) physiologically relevant ROS and RNS in the test tube [reviewed in (3)]. However, it is not clear whether LA acts directly to scavenge ROS and RNS in vivo. The highest tissue concentrations of free LA likely to be achieved through oral supplementation are at least 10 times lower than those of other intracellular antioxidants, such as vitamin C and glutathione. Moreover, free LA is rapidly eliminated from cells, so any increases in direct radical scavenging activity are unlikely to be sustained.

Regeneration of Other Antioxidants: When an antioxidant scavenges a free radical, it becomes oxidized itself and is not able to scavenge additional ROS or RNS until it has been reduced. DHLA is a potent reducing agent with the capacity to reduce the oxidized forms of several important antioxidants, including vitamin C and glutathione (20). DHLA may also reduce the oxidized form of alpha-tocopherol (the alpha-tocopheroxyl radical) directly or indirectly, by reducing the oxidized form of vitamin C (dehydroascorbate), which is able to reduce the alpha-tocopheroxyl radical (21). Coenzyme Q10 is an important component of the mitochondrial electron transport chain that also has antioxidant activity. DHLA can also reduce oxidized forms of coenzyme Q10 (22), which may also reduce the alpha-tocopheroxyl radical (23). Although DHLA has been found to regenerate oxidized antioxidants in the test tube, it is not known whether DHLA effectively regenerates other antioxidants under physiological conditions (3).

Metal Chelation: Redox-active metal ions, such as free iron and copper, can induce oxidative damage by catalyzing reactions that generate highly reactive free radicals (24). Compounds that chelate (bind) free metal ions in a way that prevents them from generating free radicals offer promise in the treatment of neurodegenerative and other chronic diseases, in which metal-induced oxidative damage may play a role (25). Both LA and DHLA have been found to inhibit copper- and iron-mediated oxidative damage in the test tube (26, 27), and to inhibit excess iron and copper accumulation in animal models (28, 29).

Induction of Glutathione Synthesis: Glutathione is an important intracellular antioxidant that also plays a role in the detoxification and elimination of potential carcinogens and toxins. Studies in animals have found that glutathione synthesis and tissue glutathione levels are significantly lower in aged animals than in younger animals, leading to decreased ability of aged animals to respond to oxidative stress or toxin exposure (30). LA has been found to increase glutathione synthesis in cultured cells and in the tissues of aged animals fed LA. Recent research suggests that LA may increase glutathione synthesis in aged animals by increasing the expression of gamma-glutamylcysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis (31) and by increasing cellular uptake of cysteine, an amino acid required for glutathione synthesis (32).

Adverse Effects

In general, LA supplementation has been found to have few serious side effects. Intravenous administration of racemic LA at doses of 600 mg/day for 3 weeks (53) and oral racemic LA at doses as high as 1800 mg/day for 6 months (56) and 1200 mg/day for 2 years (55) did not result in serious adverse effects when used to treat diabetic peripheral neuropathy. Two minor anaphylactoid reactions and one severe anaphylactic reaction, including laryngospasm, were reported after intravenous LA administration (40). The most frequently reported side effects to oral LA supplementation are allergic reactions affecting the skin, including rashes, hives and itching. Gastrointestinal symptoms, including abdominal pain, nausea, vomiting and diarrhea have also been reported. Malodorous urine has also been noted by people taking 1200 mg/day of LA orally (60).

Parkinson's disease
Co-Q10
Parkinson's disease is a degenerative neurological disorder characterized by tremors, muscular rigidity, and slow movements. It is estimated to affect approximately 1% of Americans over the age of 65. Although the causes of Parkinson's disease are not all known, decreased activity of complex I of the mitochondrial electron transport chain and increased oxidative stress in a part of the brain called the substantia nigra are thought to play a role. Coenzyme Q10 is the electron acceptor for complex I as well as an antioxidant, and decreased ratios of reduced to oxidized coenzyme Q10 have been found in platelets of individuals with Parkinson's disease (55, 56). A 16-month randomized placebo-controlled trial evaluated the safety and efficacy of 300, 600, or 1200 mg/d of coenzyme Q10 in 80 people with early Parkinson's disease (57). Coenzyme Q10 supplementation was well tolerated at all doses and was associated with slower deterioration of function in Parkinson's disease patients compared to placebo. However, the difference was statistically significant only in the group taking 1200 mg/d. More recently, a small placebo-controlled trial showed that oral administraton of 360 mg/d of coenzyme Q10 for four weeks moderately benefited Parkinson's disease patients (58). Although these preliminary findings are promising, they need to be confirmed in larger clinical trials before recommending the use of coenzyme Q10 in early Parkinson's disease.


organic coffee
Parkinson’s Disease

Several large prospective cohort studies have found higher coffee and caffeine intakes to be associated with significant reductions in Parkinson’s disease risk in men (18-20). In a prospective study of 47,000 men, those who regularly consumed at least one cup of coffee daily had a risk of developing Parkinson’s disease over the next 10 years that was 40% lower than men who did not drink coffee (19). Caffeine consumption from other sources was also inversely associated with Parkinson’s disease risk in a dose-dependent manner. Studies in animal models of Parkinson’s disease suggest that caffeine may protect dopaminergic neurons by acting as an adenosine A2A-receptor antagonist in the brain (21). In contrast to the results of prospective studies in men, inverse associations between coffee or caffeine consumption and Parkinson’s disease risk were not observed in women (18, 19). The failure of prospective studies to find inverse associations between coffee or caffeine consumption and Parkinson’s disease in women may be due to the modifying effect of estrogen replacement therapy. Further analysis of a prospective study of more than 77,000 female nurses revealed that coffee consumption was inversely associated with Parkinson’s disease risk in women who had never used postmenopausal estrogen, but a significant increase in Parkinson’s disease risk was observed in postmenopausal estrogen users who drank at least 6 cups of coffee daily (22). In a prospective cohort study that included more than 238,000 women, a significant inverse association between coffee consumption and Parkinson’s disease mortality was also observed in women who had never used postmenopausal estrogen, but not in those who had used postmenopausal estrogen (18). It is not known how estrogen modifies the effect of caffeine on Parkinson’s disease risk (23). Although the results of epidemiological and animal studies suggest that caffeine may reduce the risk of developing Parkinson’s disease, it is premature to recommend increasing caffeine consumption to prevent Parkinson’s disease, particularly in women taking estrogen.

flavinoids
Neurodegenerative Disease

Inflammation, oxidative stress and transition metal accumulation appear to play a role in the pathology of several neurodegenerative diseases, including Parkinson's disease and Alzheimer’s disease. Because flavonoids have anti-inflammatory, antioxidant and metal chelating properties, scientists are interested in the neuroprotective potential of flavonoid-rich diets or individual flavonoids. At present, the extent to which various dietary flavonoids and flavonoid metabolites cross the blood brain barrier in humans is not known (84). Although flavonoid-rich diets and flavonoid administration have been found to prevent cognitive impairment associated with aging and inflammation in some animal studies (85-88), prospective cohort studies have not found consistent inverse associations between flavonoid intake and the risk of dementia or neurodegenerative disease in humans (89-93). In a cohort of Japanese-American men followed for 25-30 years, flavonoid intake from tea during midlife was not associated with the risk of Alzheimer’s or other types of dementia in late life (89). Surprisingly, higher intakes of isoflavone-rich tofu during midlife were associated with cognitive impairment and brain atrophy in late life (see Soy Isoflavones) (90). A prospective study of Dutch adults found that total dietary flavonoid intake was not associated with the risk of developing Parkinson disease (91) or Alzheimer’s disease (92), except in current smokers whose risk of Alzheimer’s disease decreased by 50% for every 12 mg increase in daily flavonoid intake. In contrast, a study of elderly French men and women found that those with the lowest flavonoid intakes had a risk of developing dementia over the next 5 years that was 50% higher than those with the highest intakes (93). Although scientists are interested in the potential of flavonoids to protect the aging brain, it is not yet clear how flavonoid consumption affects neurodegenerative disease risk in humans.

Sources

Food Sources

Dietary sources of flavonoids include tea, red wine, fruits, vegetables and legumes. Individual flavonoid intakes may vary considerably depending on whether tea, red wine, soy products or fruits and vegetables are commonly consumed [reviewed in (3)]. Although individual flavonoid intakes may vary, total flavonoid intakes in Western populations appear to average about 150-200 mg/day (3, 94). Information on the flavonoid content of some flavonoid-rich foods is presented in table 2 and table 3. These values should be considered approximate since a number of factors may affect the flavonoid content of foods, including agricultural practices, environmental factors, ripening, processing, storing and cooking. For more information about the flavonoid content of foods, see the USDA databases for the flavonoid and proanthocyanidin content of selected foods. For information on the isoflavone content of soy foods, see the separate article on Soy Isoflavones or the USDA database for the isoflavone content of selected foods.

Table 2. Anthocyanin, Flavanol and Proanthocyanidin Content of Selected Foods

Table 3. Flavone, Flavonol and Flavanone Content of Selected Foods

Supplements

Anthocyanins

Bilberry, elderberry, black currant, blueberry, red grape and mixed berry extracts that are rich in anthocyanins are available as dietary supplements without a prescription in the U.S. The anthocyanin content of these products may vary considerably. Standardized extracts that list the amount of anthocyanins per dose are available.

Flavanols

Numerous tea extracts are available in the U.S. as dietary supplements, and may be labeled as tea catechins or tea polyphenols. Green tea extracts are the most commonly marketed, but black and oolong tea extracts are also available. Green tea extracts generally have higher levels of catechins (flavanol monomers), while black tea extracts are richer in theaflavins and thearubigins (flavanol polymers found in tea). Oolong tea extracts fall somewhere in between green and black tea extracts with respect to their flavanol content. Some tea extracts contain caffeine, while others are decaffeinated. Flavanol and caffeine content vary considerably among different products, so it is important to check the label or consult the manufacturer to determine the amounts of flavanols and caffeine that would be consumed daily with each supplement. (For more information on tea flavanols, see the article on Tea.)

Flavanones

Citrus bioflavonoid supplements may contain glycosides of hesperetin (hesperidin), naringenin (naringin) and eriodictyol (eriocitrin). Hesperidin is also available in hesperidin-complex supplements (95).

Flavones

The peels of citrus fruits are rich in the polymethoxylated flavones, tangeretin, nobiletin and sinensetin (3). Although dietary intakes of these naturally occurring flavones are generally low, they are often present in citrus bioflavonoid supplements.


Neurodegenerative Disease

Although it is not yet clear whether a diet rich in fruits and vegetables will decrease the risk of neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease in humans, recent studies in animal models of these diseases suggest that diets high in fruits like blueberries (49) or tomatoes may be protective (50).


Neurodegenerative disease

Iron is required for normal brain and nerve function through its involvement in cellular metabolism, as well as the synthesis of neurotransmitters and myelin. However, accumulation of excess iron can result in increased oxidative stress, and the brain is particularly susceptible to oxidative damage. Iron accumulation and oxidative injury are presently under consideration as potential contributors to a number of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease (36). The abnormal accumulation of iron in the brain does not appear to be a result of increased dietary iron, but rather, a disruption in the complex process of cellular iron regulation. Although the mechanisms for this disruption in iron regulation are not yet known, it is presently an active area of biomedical research (37).

Drug Interactions

Medications that decrease stomach acidity, such as antacids, histamine (H2) receptor antagonists (e.g., cimetidine, ranitidine), and proton pump inhibitors (e.g., omeprazole, lansoprazole), may impair iron absorption. Taking iron supplements at the same time as the following medications may result in decreased absorption and efficacy of the medication: levodopa, levothyroxine, methyldopa, penicillamine, quinolones, tetracyclines, and bisphosphonates. Therefore, it is best to take these medications two hours apart from iron supplements. Cholestyramine resin, used to lower blood cholesterol levels, should also be taken two hours apart from iron supplements because it interferes with iron absorption. Allopurinol, a medication used to treat gout, may increase iron storage in the liver and should not be used in combination with iron supplements (23, 38).

Linus Pauling Institute Recommendation

Following the most recent RDA for iron should provide sufficient iron to prevent deficiency without causing adverse effects in most individuals. Although sufficient iron can be obtained through a varied diet, a considerable number of people do not consume adequate iron to prevent deficiency. A multivitamin/multimineral supplement containing 100% of the daily value (DV) for iron provides 18 mg of elemental iron. While this amount of iron may be beneficial for premenopausal women, it is well above the RDA for men and most postmenopausal women.

Adult men and postmenopausal women

Since hereditary hemochromatosis is relatively common and the effects of long-term dietary iron excess on chronic disease risk are not yet clear, men and postmenopausal women who are not at risk of iron deficiency should take a multivitamin/mineral supplement without iron. A number of multivitamins formulated specifically for men or those over 50 years of age do not contain iron.

Adults over the age of 65

A recent study in an elderly population found that high iron stores were much more common than iron deficiency (39). Thus, older adults should not generally take nutritional supplements containing iron unless they have been diagnosed with iron deficiency. Moreover, it is extremely important to determine the underlying cause of the iron deficiency, rather than simply treating it with iron supplements.

References


--------------------------------------------------------------------------------

Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

I am amazed to find Dr. Perlmutter article goes back to 2001 : YES !!, why has it been ignored ? ONLY TO HAVE NEW RESEARCH TO SUPPORT IT.
WE WPD'S SHOULD MAKE SOME NOISE SO THAT THE ISSUE IS EXAMINED AND THE TRUTH TOLD

http://www.encyclopedia.com/doc/1G1-76445678.html

New Advances in Parkinson's Disease.
From: Townsend Letter for Doctors and Patients | Date: 7/1/2001 | Author: Perlmutter, David
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It has been estimated that in the United States alone more than 1 million people have Parkinson's disease, with more than 50,000 new cases being diagnosed each year. That translates to a prevalence of about 1-2 cases per 1000 individuals in the general population. This prevalence increases dramatically when looking at the over-55 population, approaching 1 in 100. The average age of onset is about 60 years, but it may be diagnosed as early as the mid 30's. [1] Perhaps because of some brain protective effects of female hormones, men are slightly more at risk than women.

Symptoms of Parkinson's disease vary from patient to patient but typically include tremor, rigidity, slowness of movement, and disturbances of posture. The tremor of the Parkinsonian patient is somewhat characteristic in that unlike other forms of tremor, it is worse at rest and may improve substantially when the affected limb is used. It is worse with stress and typically begins on one side, usually affecting the hand. Thereafter, the opposite hand may become involved as well as other parts of the body, including the legs, facial muscles and even the tongue.

The rigidity in Parkinson's may involve any of the major limbs. Typically there is increased tone throughout the range of motion of the involved joint.

Slowness of movement, technically known as bradykinesia, is another hallmark of the disease and can be one of the most incapacitating symptoms. Patients report difficulty in initiating movements and may have great difficulty in arising from a chair or starting to walk when standing. They may describe a sensation of feeling like they are wearing "cement boots," or that their feet are "magnetic." Facial expressions are reduced, and it may be difficult to begin speaking. The handwriting may become smaller and patients may find it difficult to turn over in bed.

As the disease progresses, the posture becomes affected with increased forward flexion at the waist and a tendency to stand and walk in a stooped position. As Dr. James Parkinson described in his original 1817 monograph:

"After a few more months the patient is found to be less strict in preserving the upright posture: this being most observable whilst walking, but sometimes whilst sitting or standing. Sometime after the appearance of this symptom, and during its slow increase, one of the legs is discovered slightly to tremble, and is also found to suffer fatigue sooner than the leg of the other side: and in a few months this limb becomes agitated by similar tremblings, and suffers a similar loss of power." [2]

The Glutathione Miracle

It has long been recognized that a fundamental abnormality in Parkinson's disease patients is the failure of a specific part of the brain, the substantia nigra, to produce an important brain chemical, the neurotransmitter dopamine. Focusing on this specific chemical flaw, the pharmaceutical industry has developed a wide array of medications to provide symptomatic relief.

In 1959 the first true therapeutic approach to treating the symptoms of Parkinson's disease was proposed, attempting to replace dopamine. This is the basis for the use of the dopamine derivative L-dopa (Sinemet[R]) in the treatment of Parkinson's disease symptoms today. [3] Indeed, even today L-dopa therapy remains the mainstay of treatment. Unfortunately, while L-dopa therapy may help to temporarily reduce the symptoms of Parkinson's disease, many scientific reports are now appearing in medical journals warning that L-dopa therapy may actually increase free radical production and thus speed up the progression of the illness, causing patients to worsen more quickly. [4]

With so much emphasis placed on L-dopa therapy, it is important to recognize that another vital brain chemical is also profoundly deficient in Parkinson's disease. This chemical, glutathione, is substantially reduced, virtually across the board, in Parkinson's patients. And yet, this deficiency seems to receive precious little attention. [5]

Glutathione is a critically important brain chemical. It is clearly one of the most important brain antioxidants. That is, glutathione helps to preserve brain tissue by preventing damage from free radicals - destructive chemicals formed by the normal processes of metabolism, toxic elements in the environment, and as a normal response of the body to challenges by infectious agents or other stresses. In addition to quenching dangerous free radicals, glutathione also acts to recycle vitamin C and vitamin E, which, because of their antioxidant activity, also reduce free radicals in the brain.

So, with the understanding that glutathione is important for brain protection, and that this protection may be lacking in the brains of Parkinson's patients because of their glutathione deficiency, wouldn't it make sense to give glutathione to Parkinson's patients experimentally and observe their outcome? That's exactly what was done in a landmark study from the Department of Neurology, University of Sassari, Italy. In this research protocol Parkinson's patients received intravenous glutathione twice daily for 30 days. The subjects were then evaluated at one month intervals for up to six months. The published results indicated "all patients improved significantly after glutathione therapy, with a 42% decline in disability. Once glutathione was stopped the therapeutic effect lasted 2-4 months." Further, the researchers indicated "...glutathione has symptomatic efficacy and possibly retards the progression of the disease." [6]

It is unclear exactly why this study has remained almost completely unrecognized. In the United States, the use of L-dopa, or other drugs designed to mimic it, remains the standard of care. And yet, this Italian study demonstrated that providing glutathione, a substance naturally occurring in the brain, provided Parkinson's patients substantial benefit.

Glutathione as such, cannot be patented. So it cannot be owned exclusively by any particular pharmaceutical company and therefore won't find its way to the highly influential advertising sections of the medical journals. And yet, quite simply we know that the brains of Parkinson's patients are profoundly deficient in this important chemical, with clinical research supporting its incredible effectiveness.

We began administering intravenous glutathione in late 1998. The effectiveness of this brain antioxidant in Parkinson's disease is nothing short of miraculous. Certainly, its administration is more complicated than simply "taking a pill," but on the other hand, there are essentially no reported side effects. In addition, while our Parkinson's patients are now realizing profound improvements with respect to reduction of rigidity, increased mobility, improved ability to speak, less depression, and decreased tremor, glutathione has the added benefit of protecting the brain from free radical damage, thus slowing the progression of the underlying illness. This contrasts vividly with the simplistic approach of only treating symptoms while potentially worsening the underlying disease.

Following even a single dosage of intravenous glutathione, many of the symptoms of Parkinson's disease are rapidly improved, often in as little as 15 minutes. Injections are typically repeated from 3 times a week to as often as daily.

Here is an example of a typical response to glutathione therapy in a patient with moderately advanced Parkinson's disease:

Dear Dr. Perlmutter:

This letter is to advise you of the progress of my husband's response to the glutathione therapy started two weeks ago.

As you know (HS), now 72 years old, had been diagnosed with Parkinson's disease five years ago, starting with a tremor in his right hand. The disease progressed rapidly, impairing his walking ability, balance, and reducing his voice volume and clarity. Most recently, his inability to walk had made it necessary for him to use a wheelchair when leaving the house. At home, he has used a walker for the past two years.

His prescribed medications have included Sinemet [R], Mirapex [R], and Tasmar [R] over the past years, the effects of which have diminished.

Almost immediately after your first treatment of glutathione IV two weeks ago, there was a marked improvement in his facial expression, his voice volume, and ability to walk and turn. He started with 400 mg., 3 times a week. The effective period of time after injection has increased from one hour to almost the whole day. When we visited your office last he received 600 mg., and his ability to walk almost normally lasted the full day and part of the next.

He also reports that he has a general feeling of wellbeing after each treatment. And he is now taking 400 units of glutathione IV once a day, together with the supplements you have prescribed.

We are thrilled to report that he has not used the wheelchair for the past two days and is able to take full strides with his arm linked in mine. His facial expression is animated and his voice volume has increased.

In addition, we have cut back on his intake of Sinemet[R] and stopped the Tasmar[R]. In the past, without the Sinemet[R], he had been unable to walk -- his legs practically frozen. With the glutathione therapy, he can walk with a reduced intake of Sinemet[R].

We feel our prayers have been answered, that there is something positive that can be done to fight and arrest this dreadful disease now. We cannot thank you enough for the hope you have given us and we will keep you informed as to his progress until the next office visit.

Most consider Parkinson's disease to be an affliction only of the elderly. But we are now seeing patients in their 50's, 40's, and even 30's, with regularity. Here is a report from a 57-year-old plastic surgeon and former marathon runner:

Dear David:

This is a followup since my visit with you in April of 1999. As you will recall, my symptoms were those of micrographia (small handwriting), drooling, exhaustion, tremor, inanimate facies, poor voice projection and modulation, and depression. Your diagnosis was that of Parkinson's disease. I was started on glutathione 400 mg, three times a week, and I was instructed to take vitamins D, E, and B12 in addition to my rather extensive vitamin and herbal supplementation program.

I received my first dose of glutathione in your office that day and within two hours I felt like a new person. I was more animate and expressive almost immediately. Over the next few weeks, my voice became stronger, I felt less tired and my tremor almost disappeared. More slowly, my writing has improved; it's not perfect (never was) but at least with effort and slowing down, I can write legibly now. I still tend to drool some but even that is much improved. My energy is not totally back to normal but I am working a full schedule as a plastic surgeon with a very busy practice. My depression is gone and I have my sense of humor back.

When I was originally diagnosed at Duke, I was given a prescription for Sinemet[R] and advised to get my affairs in order. Your approach has kept me off this medication, almost restored me to normal, and more importantly, has given me hope that we may slow the progression of my disease if not halt it altogether.

I want you to know how very much I appreciate your care, your caring, and your pioneering efforts.

Thank you

There are several factors that explain why glutathione is so beneficial in Parkinson's disease. First, glutathione has the unique ability to make certain areas of the brain more sensitive to dopamine, so that even though dopamine is decreased, it nevertheless becomes more effective. [7] The concept of enhancing cellular receptor sensitivity has become quite familiar in medicine today. In diabetes for example, before actually administering insulin, physicians often begin therapy by prescribing the drug metformin, which acts by enhancing the sensitivity of cells to whatever insulin is still being produced.

In addition, as mentioned above, glutathione has profound antioxidant activity -- protecting the brain from free radical damage. But an even more intriguing benefit of glutathione lies not in the brain but in an area of the body far beyond the scope of typical neurology.

The Liver Connection

Glutathione is one of the most important components of the liver's detoxification system. It has long been recognized that most Parkinson's patients manifest flaws in their ability to detoxify various chemicals to which they are exposed. This is the obvious explanation as to why Parkinson's disease is so much more prevalent in individuals with a history of occupational exposure to agricultural pesticides or various other toxic chemicals. [8] While not every person exposed to pesticides or other toxins develops Parkinson's disease, those unfortunate few who harbor an inherited flaw in their detoxification pathways are at far greater risk to the brain damaging effects of a wide variety of toxins as we described in 1997. [9]

Giving glutathione is one of the most effective techniques for enhancing liver and brain detoxification. The nutritional supplement N-acetyl-cysteine, (often abbreviated NAC), enhances the body's production of glutathione and thus aids the detoxification process. Other nutritional supplements which enhance glutathione and thus aid in detoxification include vitamins E and C, alpha lipoic acid, and the herb silymarin.

UltraClear Plus[TM] a nutritional supplement designed by Dr. Jeffery S. Bland, has been extensively evaluated in clinical studies and has been found to significantly enhance liver detoxification. [10] We use this product as first line therapy when we identify individuals with abnormalities of detoxification.

Enhancing liver detoxification can have a dramatic effect on the manifestations of Parkinson's disease as exemplified by the following case history:

B.K. is a 40-year-old male who, in 1989 at the age of 34, began experiencing a tremor of the right hand. This was associated with micrographia (small handwriting) and the subsequent development of a right leg tremor. Over the next several years he developed slowness of movement, a reduction of facial expression, and a prominent loss of arm swinging when walking. He was placed on a sustained release preparation of L-dopa (Sinemet CR[R]) which produced a definite improvement of his symptoms.

When evaluated on 10/10/95, his medications included sustained release L-dopa (Sinemet CR[R] 25/100) three times each day, standard release L-dopa (Sinemet 25/100) twice each day, selegiline (Eldepryl [R]) 5 mg twice each day, and bromocriptine (Parlodel[R]) 5 mg twice a day. As with many of our patients, a videotape recording was made to document his clinical status.

His past medical history revealed that he had lived directly adjacent to a large commercial pesticide-using farm for the first twelve years of his life, and he recalled how he and his friends would follow the pesticide spraying tractors through the corn fields for fun.

On 02/06/96, the patient began a two week nutritional program designed to improve liver detoxification. After the initial two weeks the patient reported, "My medications are working better and I have much less rigidity and tremor." These findings were confirmed on the physical examination. Videotape recording was made prior to and subsequent to the treatment protocol, and a significant improvement was also noted in fluidity of movement, facial expression, and arm movement with walking. Perhaps even more impressive was the fact that these improvements persisted even after the medications were markedly reduced.

At followup examination three years after the initial detoxification he demonstrated continued improvement of clinical symptoms compared to his initial videotaped exam, and he remains on a reduced schedule of medications.

Evaluating an individual's detoxification status is easily accomplished using a very simple test, the Hepatic Detoxification Profile available from the Great Smokies Diagnostic Laboratory in Asheville, North Carolina (see below). The test involves the oral administration of several over-the-counter challenge substances. Subsequently, saliva, urine and blood are collected and analyzed to determine how these substances are metabolized. The results provide an extremely comprehensive picture of the various liver detoxification pathways, allowing the treating physician to design a specific interventional program to improve liver function.

Finally, keep in mind that certain drugs can reduce liver detoxification function. Acetaminophen, a drug commonly used for pain and fever, can actually reduce liver glutathione and should therefore be avoided. [11] It is found in a large number of over-the-counter and prescription medications so pay close attention to labels.

Cellular Activation

During the 1990's, the so-called "Decade of the Brain," scientists learned that the fundamental flaw not allowing certain brain cells to produce dopamine in the Parkinson's patient is a deficiency in the actual energetics of these cells. It is as if these cells, while still alive, are simply unable to produce the energy needed for normal activity. Incredibly, the most widely prescribed medication for Parkinson's disease, L-dopa (Sinemet[R]), has been shown to actually lead to further compromise of the brain's ability to produce energy. [12] This further reduces the production of dopamine, leading to worsening of the disease.

With a formal understanding of the biochemistry of energy production, researchers have explored a variety of interventions designed to "jump start" these lethargic cells, often with dramatic results. And best of all, most of the research has involved non-pharmacological products. The most promising of these cellular activators are NADH, CoQ10, and phosphatidylserine.

NADH (Nicotinamide Adenine Dinucleotide)

NADH is an enzyme which has a pivotal role in energy production in all living cells, and particularly in brain cells. The amount of energy a cell can produce is directly related to NADH availability. Since Parkinson's disease represents a failure of cellular energy production, it's reasonable that researchers would take a look at NADH as a potential therapeutic agent.

Pioneering work published by Dr.Jorg Birkmayer in 1993 revealed just how potent NADH can be as part of a comprehensive program for the Parkinson's patient. Of 885 patients who received NADH in his study, an astounding 80% showed "moderate to excellent improvements in their disability." [13] This shouldn't come as a surprise given NADH's profound effectiveness in other neurological disorders including Alzheimer's disease.

Coenzyme Q10 (CoQ10)

The other important player in energy production is CoQ10. Like NADH, CoQ10 is also present in all living cells where it too plays a critical role in cellular energy production. Energy deficiencies in specific parts of the brain can produce inadequate production of important brain chemicals. And, according to Dr. M. Flint Beal at the Massachusetts General Hospital, Parkinson's patients demonstrate a profound deficiency of coenzyme Q10 which may explain why their brains produce an inadequate supply of dopamine. Interestingly, Dr. Beal's research revealed that not only was coenzyme Q10 deficient in Parkinson's patients, but in their spouses as well -- although to a lesser extent (see figure 1.1). [14] This unexpected finding lends further support to the concept that Parkinson's disease may in some way be related to some extrinsic environmental factor.

The encouraging news from Dr. Beal's research is that orally administered CoQ10 is readily absorbed, well tolerated, and measurably increases cellular energy production. These qualities, coupled with its profound antioxidant properties, likely explain why the therapeutic potential of CoQ10 in Parkinson's disease is now the subject of intensive research at major medical institutions all across the country.

Finally, recognizing the importance of coenzyme Q10 makes it critical to identify any factors which may lower its availability. Unfortunately, two of the most commonly prescribed cholesterol lowering drugs, pravastatin (Pravachol[R]) and lovastatin (Mevacor[R]), dramatically lower serum coenzyme Q10 levels. [16]

Phosphatidylserine

Phosphatidylserine is one of the key components of neuronal membranes -- the site where brain cells both receive and transmit chemical messages. Enhancing chemical transmission is of obvious importance in Parkinson's disease, an illness in which the fundamental abnormality is a flaw in the ability of neurons to communicate chemically because of a deficiency of dopamine. Even in the face of this deficiency, increasing phosphatidyl-serine may enhance the effectiveness of what little dopamine remains -- helping to preserve brain function.

The energy-producing mitochondria also rely upon a healthy membrane to carry out the function of energy production. Like the cellular membrane, the mitochondrial membrane requires adequate phosphatidylserine to maintain normal function.

It has been estimated that as many as 30% of Parkinson's disease patients suffer from a progressive decline not only in motor function, but in cognitive ability as well. At times the dementia associated with the disease is more debilitating than the common problems of tremor, rigidity and balance disorders. This further supports the inclusion of phosphatidylserine in treating Parkinson's disease since research supports its profound therapeutic potential in dementia. This was confirmed in a 1991 article in the journal Neurology in which researchers from Stanford University demonstrated a marked improvement on performance tests related to memory and learning in a group of 149 memory impaired patients treated with phosphatidyl-serine for 12 weeks. [17]

Antioxidant Protection

As in other neurodegenerative diseases, antioxidants have an important role in protecting the brain in Parkinson's disease - a disease characterized by excessive free radical production coupled with deficient antioxidant defenses. This is not a new concept. The research exploring both the role of free radicals and the protective effects of antioxidants in diseases like Parkinson's goes back at least 2 decades. In a 1988 report entitled "Case-control study of early life dietary factors in Parkinson's disease" published in Archives of Neurology, researchers discovered that simple dietary sources of vitamin E profoundly reduced the risk of Parkinson's disease. Compared to controls, those who consumed diets rich in nuts had a risk of Parkinson's disease only 39% of controls. Consumers of seed based salad dressings had a risk only 30% of normal, while consumption of plums was associated with a risk reduced to an incredible 24% of the average population. [18]

Retrospective epidemiological studies like these have prompted research to determine if administering antioxidants could slow the progression of disease in those already diagnosed. Dr. Stanley Fahn, one of the country's most highly respected neurologists and chairman of the Department of Neurology at Columbia University College of Physicians and Surgeons, evaluated the effectiveness of vitamins E and C in a large group of Parkinson's patients over several years. At the beginning of the study, none of the patients was debilitated enough to need the standard Parkinson's drug, L-dopa (Sinemet[R]). The time until patients required L-dopa therapy was extended an incredible 2.2 years in those taking these simple nonprescription vitamins. [19]

These results clearly indicate the power of antioxidants to slow the progression of Parkinson's disease. Shouldn't this information be provided to all Parkinson's patients and their families? Unfortunately, vitamin and nutritional information is not typically conveyed on the prescription pad -- the ultimate coin of medical commerce.

Below is a descriptive list of powerful brain antioxidants, key players in the BrainRecovery.com protocol for Parkinson's disease.

Alpha Lipoic Acid

The subject of intensive study in the neurodegenerative diseases, alpha lipoic acid not only serves as an extremely powerful antioxidant in and of itself, but in addition, it regenerates vitamins C and E as well as glutathione. But unlike glutathione, which isn't useful when given orally, alpha lipoic acid is readily absorbed from the gut and has the unique ability to cross the blood-brain barrier and enter the central nervous system.

Yet another quality of alpha lipoic acid is its ability to serve as a metal chelator. That means it can bind to a variety of potentially toxic metals in the body, including cadmium and free iron, and enhance their excretion. This is an important function since these metals may increase the formation of damaging free radicals and research demonstrates substantially increased concentrations of iron in the brains of Parkinson's patients. [20]

Vitamin E

Since cell membranes and the brain in general contain large amounts of fat, vitamin E, a "fat-soluble" vitamin is particularly important in protecting the nervous system. This important brain antioxidant remains the focus of world wide scientific evaluation for its therapeutic potential in Parkinson's disease, Alzheimer's disease and various other neurodegenerative conditions. Since Dr. Fahn's original publication in 1989, countless other researchers have confirmed the antioxidant power of this inexpensive nutritional supplement.

When buying vitamin E, always read the label carefully to ensure you are getting d-alpha tocopherol, not dl-alpha tocopherol, since the latter is synthetic and far less biologically active. Also, always refrigerate vitamin E and all other oil-based nutritional supplements to preserve their potency.

N-acetyl-cysteine (NAC)

The critical role of glutathione in the development and progression of Parkinson's disease cannot be overemphasized. While glutathione cannot be administered orally since it is readily digested to its constituent amino acids, the good news is that the nutritional supplement N-acetyl-cysteine directly encourages brain glutathione production. This activity is enhanced in the presence of adequate vitamin C and vitamin E. In addition, NAC itself is a potent antioxidant and has been shown to specifically reduce the formation of the free radical nitric oxide, which has been implicated as having a causative role in Parkinson's disease, Alzheimer's disease, and several other neurodegenerative disorders. [21] Consideration of the brain damaging effects of nitric oxide is particularly timely in view of the popularity of the drug Viagra[R] which works by enhancing nitric oxide production.

Acetyl-L-carnitine

Like coenzyme Q10 and NADH, acetyl-L-carnitine enhances energy production in damaged neurons. But in addition, it is one of the most important and specific antioxidants in the BrainRecovery.com protocol for Parkinson's disease. In a fascinating study reported in 1995, researchers demonstrated the ability of acetyl-L-carnitine to completely prevent parkinsonism in laboratory animals. When laboratory animals are exposed to the brain toxin MPTP, they immediately develop full-blown parkinsonism as a consequence of enhanced production of destructive free radicals specifically in the brain area that produces dopamine. Pre-treating the animals with acetyl-L carnitine prior to MPTP exposure offered complete protection - none of the animals developed parkinsonism. This study affirmed the potency of acetyl-L-carnitine as an antioxidant specifically useful in Parkinson's disease. [22]

Vitamin D

Although widely recognized for its role in maintaining healthy bones, vitamin D has recently become the subject of scientific interest since it too has been found to be an important antioxidant, possibly even more potent than vitamin E. In a recent (1997) study reported in the journal Neurology, Japanese researchers found surprisingly low levels of vitamin D in the blood of the 71 Parkinson's patients they evaluated. Not recognizing the important antioxidant, and therefore brain protecting activity of vitamin D, these researchers simply concluded that because of their low vitamin D levels, Parkinson's disease patients are at higher risk for osteoporosis. [23,24]

Ginkgo biloba

While widely known for its effectiveness in Alzheimer's disease, Ginkgo biloba must be included in this protocol as it too has profound brain antioxidant activity. Like acetyl-L-carnitine, Ginkgo biloba can also protect laboratory animals against the Parkinson's producing effect of the neurotoxin MPTP. [25] While humans are not typically exposed to this toxin, the idea that Parkinson's disease may be related to some other agent(s) is obviously supported by the profound increased incidence of the disease in those exposed to herbicides and other chemical agents as described above. Further, since dementia frequently complicates Parkinson's disease, inclusion of Ginkgo in the Parkinson's program makes sense, as this herb has been shown in extensive worldwide studies to enhance and preserve cognitive performance.

Vitamin C

Rounding out the list of antioxidants for Parkinson's disease is vitamin C. Having proven itself to be effective in slowing the progression of this disease in Dr. Fahn's original research, vitamin C, like vitamin E, became the focus of extensive research not only in Parkinson's, but in other progressive brain disorders as well. Its specific utility in Parkinson's disease was emphasized in a study also performed by Dr. Fahn and colleagues in which it was found that vitamin C helped preserve the energy-producing capacity of the mitochondria -- an abnormality actually made worse by the administration of L-dopa, the most widely prescribed drug for Parkinson's disease in the country. [26]

BrainRecovery.com -- Parkinson's Protocol

Intravenous Glutathione

Our protocol for using glutathione is relatively simple. Glutathione is inexpensive and easily obtained (see below). We use liquid glutathione, not reconstituted powder. It should be administered, at least initially, by a qualified healthcare practitioner as follows:

1. Dilute the appropriate dosage of glutathione liquid in 10 cc of sterile normal saline. Usually, vials contain 200mg, but read the label.

2. This solution is then injected through a 21-gauge butterfly catheter intravenously over a 15 to 20 minute period of time.

3. Alternatively, many patients choose to have intravenous access ports inserted. This allows frequent glutathione administration without repeated needle sticks.

4. Treatment begins at 600mg glutathione 3 times a week and may be increased to daily injections of up to 800mg depending on results. Alternatively, a schedule of 1000mg glutathione 3 times a week may be utilized.

5. An instructional videotape demonstrating glutathione administration with case reports is available at www.BrainRecovery.com or by calling: 800-530-1982

Injectable glutathione is available from: Wellness Health and Pharmaceuticals, 2800 South 18th Street, Birmingham, Alabama 35209 USA, 800-227-2627, Fax 800-369-0302.

Cellular energizers: daily dose

Coenzyme Q10: 120 mg

NADH: 5 mg (twice)

Phosphatidylserine: 50 mg

Antioxidants

Vitamin E: 1200 IU

Vitamin C: 800 mg

Alpha lipoic acid: 80 mg

Vitamin D: 400 IU

N-acetyl-cysteine: 400 mg

Acetyl-L-carnitine: 400 mg

Ginkgo biloba: 60 mg

Note:

In Parkinson's patients less than 65 years of age check liver detoxification by performing Hepatic Detoxification Profile available from Great Smokies Diagnostic Laboratory, 63 Zillicoa Street, Asheville, North Carolina 28801-9801 USA, 800-522 4762.

If hepatic detoxification abnormalities are detected:

UltraClear Plus[TM] 2 scoops twice daily Silymarin 200 mg -- twice daily

After 3 weeks discontinue UltraClear Plus[TM], continue silymarin and begin the standard BrainRecovery.com Parkinson's Protocol described above.

UltraClear Plus[TM] must be ordered by a physician and is available from Metagenics, 4403 Vineland Road, B-10, Orlando, Florida 32811 USA, 800-647 6100.

Resources

Living With Parkinson's Disease, Kathleen E. Biziere, Matthias C. Kurth, Demos Vermande; ISBN: 1888799102. Published 1997

Parkinson's: A Personal Story of Acceptance, Sandi Gordon, Lee W. Tempel, Branden Publishing Co; ISBN: 0828319499; Published 1992

Parkinson's Disease: The Complete Guide for Patients and Caregivers, A. N. Lieberman (Editor), Frank L. Williams, Fireside; ISBN: 0671768190; Published 1993

Understanding Parkinson's Disease: A Self Help Guide, David L. Cram, Addicus Books; ISBN: 0671768190; Published 1993

References

(1.) Nutt, John G. In: Porter R.G. (ed), 100 Maxims in Neurology - (2) Parkinson's Disease. St. Louis: Mosby Year Book, 1992: 1

(2.) Parkinson's, James, An Essay on the Shaking Palsy. London Whittingham and Rowland, 1817: 4

(3.) Carlsson, A: The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev 11:490-493, 1959

(4.) Graham, D.G. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14:633-43, 1978

(5.) Perry, T.L., Godin, D.V., Hansen, S.: Parkinson's disease: A disorder due to nigral glutathione deficiency? Neurosci Lett 33: 305-310, 1982

(6.) Sechi, G., Deledda, M.G., Bua, G., et al., Reduced glutathione in the treatment of early Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry 20(7): 1159-70,1996

(7.) Bains, J. S., Shaw, C.A.: Neurodegenerative disorders in humans: the role of glutathione in oxidative stressmediated neuronal death. Brain Res Rev 25 (3): 335-58, 1997

(8.) Tanner, C.M., Liver Abnormalities in Parkinson's disease. Geriatrics 46 (1): 60-63, 1991

(9.) Perlmutter, D., New Perspectives in Parkinson's Disease. Townsend Letter for Doctors 162: 48-50, 1997

(10.) Bland, J.S., and Bralley, J.A., Nutritional Upregulation of Hepatic Detoxification Enzymes. Journal of Applied Nutrition 44 (3&4): 5-15, 1992

(11.) Vendemiale, G., Grattagliano, I., Altomare, E., et al., Effect of acetaminophen on hepatic glutathione compartmentation and mitochondrial energy metabolism in the rat. Biochem Pharmacol 25:52 (8): 1147-54, 1996

(12.) Przedborski, S., Jackson-Lewia, V., Muthane, U., et al., Chronic levodopa administration alters mitochondrial respiratory chain activity. Ann Neurol 34 (5): 715-23, 1993

(13.) Birkmayer, J.G. D., et al, Nicotinamide Adenine Dinucleotide (NADH) -- A New Therapeutic Approach to Parkinson's Disease: Comparison of Oral and Parenteral Application. Acta Neurol Scand 87 (146): 32-35 1993

(14.) Schults, C.W., Haas, R.H., Passov, D., Beal, M.F., Coenzyme Q10 Levels Correlate with the Activities of Complexes I and II/III in Mitochondria from Parkinsonian and Nonparkinsonian Subjects. Ann Neurol 42:261-264,1997

(15.) Shults, C.W., Beal, M.F., Fontaine, K. et al., Absorption, tolerability and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients, Neurology 50: 793-795,1998

(16.) Mortensen, S.A., Leth, A., Agner, E., Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects of Med 18(Suppl.) S137-44, 1997

(17.) Crook, T.H., Tinklenberg, J., Yesavage, J., et al., Effects of phosphatidylserine in age-associated memory impairment. Neurology 41:644-49, 1991

(18.) Golbe, L.I., Farrell, T.M., David, P.H., Case-control study of early life dietary factors in Parkinson's disease. Arch Neurol 45(12): 1350-3, 1988

(19.) Fahn, S., The endogenous toxin theory of the etiology of Parkinson's disease and a pilot trial of high-dose antioxidants in an attempt to slow the progression of the illness. Ann N Y Acad Sci 570:186-96, 1989

(20.) Olanow, C.W., Attempts to obtain neuroprotection in Parkinson's disease. Neurology 49 (Suppl 1) S26-S33, 1997

(21.) Pahan, K., Sheikh, G.S., Nmboodiri, A.M.S., et al., Nacetyl cysteine inhibits induction of NO production by endotoxin or cytokine stimulated rat peritoneal macrophages, C6 glial cells and astrocytes. Free Radical Biology and Medicine 24(1):39-48, 1998

(22.) Steffen, V., Santiago, M., de la Cruz, C.P., et al, Effect of intraventricular injection of 1-methyl-4- phenylpyridinium protection by acetyl-L-carnitine. Human Exp Tbxicol 14:865-871,1995

(23.) Sato, Y., Kikuyama, M., Oizumi, K, High prevalence of vitamin D deficiency and reduced bone mass in Parkinson's disease. Neurology 49(5): 1273-78, 1997

(24.) Sardar, S., Chakraborty, A., Chatterjee, M., Comparative effectiveness of vitamin D3 and dietary vitamin E on peroxidation of lipids and enzymes of the hepatic antioxidant system in Sprague-Dawley rats. Int J Vitam Nutr Res 66(1):39-45, 1996

(25.) Wu, W.R., Zhu, X.Z., Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP- induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sci 65(2): 157-64, 1999

(26.) Przedborski, S., Jackson-Lewis, V., Muthane, U., et al., Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity. Ann Neurol 34 (5): 715-23, 1993

COPYRIGHT 2001 The Townsend Letter Group
This material is published under license from the publisher through the Gale Group, Farmington Hills, Michigan. All inquiries regarding rights should be directed to the Gale Group.
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if you research theselike I have in ggreat detail - it will piisss you off -
the Nobelist's have great medical knowlege how to cure many things...
cancer, PD, they have grea minds who have spent their lives trying to heal people, unfortunately -they just do not care /cures do not make as much
money -as palliative medicine or chemotherapy by Bristol meyers Squibb,
makes more than all of the rest - they are not in this to heal...
but to gain -the pharma bigwigs have paid a ransom for the thievery of our cures... they can not and refuse to feel our pain...


example -
http://tinyurl.com/29ye6t


When Tom Isaacs was 27 he was diagnosed with Parkinson's disease. The condition gradually destroys the brain's ability to control the muscles - there is no cure.

Determined to give himself the best possible prognosis, Tom embarked on a very personal journey to meet leading scientists in the hope of finding new treatments that would help him.

Three years ago it seemed he'd found the answer: a new drug GDNF (glial derived neurotrophic growth factor). A group of Parkinson's patients had been treated with GDNF at Bristol's Frenchay Hospital and their transformation had been remarkable: sufferers who'd been trapped in a living hell were suddenly able to walk, talk and smile again.

Parkinson's is caused by a shortage of dopamine, a chemical messenger involved in movement, mood and behaviour. Why this happens is still not known.

GDNF seems to work by stimulating dopamine production and preventing degeneration of the brain cells. The drug is delivered via a catheter permanently implanted in the brain. The catheter is connected to a Jaffa cake-sized pump sewn into the abdomen.

When GDNF was given to the Bristol patients the results were astonishing. 'Men who had been unable to get up out of a chair unaided were walking normally across a room. Their hand co-ordination was unbelievable, in exercises they could move their hand easily from left to right, something that had previously been impossible under the onslaught of Parkinson's,' says Tom.

So impressive were the results that the study was rolled out to North America and by September 2004, 50 patients were receiving the drug. The Parkinson's Disease Society in the UK planned to hand over £1.2 million to fund further trials in Bristol.

But suddenly, at the end of 2004, and without warning, this lifeline was snatched away. Amgen, the American drug company which holds the patent for manufacturing GDNF, claimed the drug was dangerous as it could cause brain damage and refused to continue prescribing it.

Amgen's decision has caused huge divisions within the Parkinson's community, pitting scientists against each other and leaving patients angry and frustrated.

As Tom explains: 'We were left with a situation where half the doctors involved in the studies sided with Amgen and the other half sided with the patients who wanted to keep taking the drug.

'The doctors didn't believe there was anything wrong with the drug and yet it was being taken away. They couldn't offer their patients an explanation because they did not agree there was one to give.'

Tom, now 38, had hoped to be able to have GDNF treatment himself, but is now leading the fight to get the drug back in use, and with his charity Movers and Shakers has raised more than £1 million to fund further research.

One of those desperate to be given the treatment is Stephen Waites. He was also 27 when he was told he had Parkinson's, and as his condition deteriorated, he had to give up his flourishing architecture business and relied instead on benefits.

But 30 years later in 2001, when he was 58, he became part of the Frenchay Hospital trial. He says he was given back his life. 'I was able to restart my business. I had more than 40 projects on the go and I really had taken on a new lease of life. I could drive again and even bought myself a new Jaguar.

'GDNF made me independent, and after so many years living with Parkinson's, I began to get my confidence back. It was a cure because it improved my condition more than 60 per cent - I could not ask for more than that and I was delighted.

'When I was told at the beginning of last year that the drug was being taken away I felt that they'd taken my life away along with it. I had committed myself to a huge workload and without the drug I couldn't fulfil my commitments.

'I've deteriorated since the GDNF was stopped - I can't drive any more so the Jaguar has had to go and we also had to downsize the house because I'd been able to start earning good money again but that went too.

'I was willing to sign anything to absolve Amgen of responsibility if anything went wrong, if only they'd let me keep taking GDNF, but they were having none of it.

'I've been very low mentally for the past 12 months and I just can't seem to rise above it.'

Tom adds: 'I think what hurts most is the total lack of communication by Amgen, who have put up a brick wall and won't discuss the issue. Two patients in America sued the company in an effort to gain 'compassionate access' to the drug but lost.

'It has been a crushing blow, especially as it has not been seen to be doing any harm to anyone, quite the reverse.' In the human trials in America some of the catheters became dislodged and as a result GDNF was floating around the brain instead of getting to where it was supposed to go.

'There were fears that this would give rise to antibodies in the brain which could then attack a patient's own reserves of GDNF and lead to brain damage,' says Tom.

'One or two patients on the American trial had shown up in scans as having antibodies, but their specialists said they'd had them there for three years and it hadn't done them any harm.'

Amgen also said that several monkeys that had received high does of the drug suffered irreversible brain damage, and subsequently died.

A spokesman for Amgen, David Polk, explained that the company had stopped providing GDNF because of 'serious safety concerns' and the absence of any demonstrated medical benefit.'

'Stopping the GDNF trial was an incredibly difficult decision, but given what we learned about GDNF we could not ethically continue to administer it to patients.

'We are actively pursuing further understanding of the toxicity and safety issues, as well as the possibility for a safe and effective alternate method of delivery.'

The patients understand that in a climate of litigation Amgen had to be cautious. But, says Tom, 'They believe that to take the drug from those on the trial who were willing to sign anything to stay normal and seemingly Parkinson's-free just seems cruel.'

Dr Stephen Gill, a neurosurgoen who headed the Bristol trial, says: 'GDNF is the best possible drug for Parkinson's and as close to a cure as you are going to get and our results in Bristol showed this. Unfortunately it wasn't demonstrated as well in the Amgen trials in America.

'It was when we learned that our patients would be stopped from having GDNF. The department was in tears and it was very stressful for everyone involved.

'I believe that Amgen's tests, which led to them withdrawing the drug, were inappropriate and were not a realistic test of the toxicology of a drug. I do not feel that there is a safety issue at all.'

Although the decision to withdraw GDNF may seem unfair, Dr Piers Benn, a lecturer in Medical Ethics and Law at London's Imperial College, says: 'It comes down to a risk-benefit analysis. If it's believed that the drug may produce side effects then the drug company has to operate cautiously and within the law.

'You can talk about informed consent from patients, but when someone is ill and anxious for a chance to improve their condition, they don't look at the situation objectively and don't always take into account the risk involved.'

Funded by the Movers and Shakers charity, Dr Gill and his team are investigating a safer form of delivery for the drug. Tom has also asked Mary Baker, chair of the World Health Organisation's steering committee on Parkinson's, to preside over a meeting with Amgen.

'If we can prove to Amgen that this new system is safe and effective then they would have to reconsider their decision,' he says.

Meanwhile, Tom, whose condition is managed with a cocktail of 15 tablets a day, has given up his job as a chartered surveyor and now raises funds to find a cure for Parkinson's.

He says: 'I know that neither GDNF or anything else is going to make it go away, but it can improve the quality of my life.

Tom Issacs can be heard in Chasing A Cure, Radio 4, November 8