Can anything be done about Parkinson’s Disease?

There’s nothing that will help everyone.
But there’s probably something that will help you.

This is the emerging paradigm of individualized medicine.  We are in transition from a past when we looked for “the cure” (antibiotics, vaccines) that would work universally to a future in which blood tests and computer analysis will determine exactly the right treatment for your individual metabolism.  While in that in-between space, the key will be personal experimentation.  Seek out reports of “miracle cures” in which something worked spectacularly well for just a few patients, while failing to help the others.  Find ten such miracles, and try them on yourself, one at a time.  Experiment to see what works for you.

Today’s column is motivated by news I received Friday about a long-time friend whose Parkinson’s is creeping out from medical control.  At 68, George is active and young in outlook.

 

Parkinson’s Background

Symptoms of PD include tremors, slow and uncertain movements, loss of motor control, shuffling.  There often is cognitive impairment, especially at later stages.

The cause of PD is the loss of neurons in a particular region of the mid-brain called the substantia nigra (SN), where nerve signals are translated into chemical signals.  One of the functions of these nerve cells is to secrete dopamine, a neurotransmitter.

We’re all losing neurons, but we don’t all have symptoms.  Maybe at age 50 our hand isn’t quite as steady as it was at age 30, but it’s nothing we would talk to a doctor about.  By the time “symptoms” appear, over 70% of the dopaminergic neurons are gone.

[LEF article on Parkinson’s]
[Background and new ideas from the Buck Institute’s SAGE web site]

It is agreed that the cause of PD is the loss of these nerve cells.  We might assume from the fact that that they are nerve cells in the brain that they perform their secretion function in a way that is smart, in response to activity and stimuli.  And yet, the standard medical treatment for Parkinson’s does not address the loss of this population of nerve cells, with the many functions they perform, nor does it even attempt to deliver dopamine in a smart and targeted way.  The best treatment medicine has to offer is to flood the brain with supplementary dopamine.

A few decades ago, it was thought that no new nerve growth takes place in the brain after adolescence.  We now realize that nerve growth continues lifelong, although neurogenesis slackens with age and does not keep up with nerve loss.  There are stem cells in the brain, and these can mature as neurons, or as glial cells or astrocytes that contribute vitally to brain chemistry.

A real cure for PD would be to re-grow the lost nerve cells of the SN.  Why not use stem cell therapy to regenerate the nerves?  This was a promising line of research about a decade ago [in rats, in people].  But when stem cells were injected into the brains of Parkinson’s patients, they withered on the vine.  They were perfectly good stem cells, but something was telling them to slack off.

This is the converse of a theme that researchers have encountered in many contexts.  Put an old cell in a young environment, and it acts young; conversely, put a young cell in a old environment and it acts old.  There are signal molecules–presumably carried in the blood plasma–that carry messages about age.  (This leads us back to the work of Amy Wagers and Mike and Irina Conboy and Tom Rando and Saul Vileda and Tony Wyss-Coray, all building a foundation for anti-aging therapies based on blood factors.  I have repored on the subject here, here, and here.)

Although enthusiasm has waned for stem cells as a one-stop cure for PD, the research community is continuing to refine the technology.  A transition is in effect from fetal stem cells, limited in availability by Bush-era regulations, to stem cells derived from the patient’s own cells, which have the advantage of being a perfect genetic match.  Stem cells do not have to be injected into the brain, because they have a remarkable ability to find their way to the place they are needed.  The most effective delivery at present is through the nose, or (more invasive) guided via a catheter that is threaded through arteries that lead to the brain.

 

Cell Senescence and PD

Are the lost brain cells that cause PD dying simply because their telomeres run out?  This would not seem a likely connection to make, since telomeres shorten with cell replication, and in the brain, cell replication is slow compared to blood, skin or even muscle cells.  But in a new article from Buck Institute last week, Megumi Mori reviews an unexpected connection between cell senescence and PD, documented by Judy Campisi’s research group.  Astrocytes are star-shaped glial cells, the background support substrate for the brain which create the proper chemical environment for neurons.  Astrocytes grow and are replaced continually during a lifetime, and hence their telomeres shorten with age.  Aging astrocytes become senescent cells, and secrete inflammatory toxins–the so-called Senescent-Associated Secretory Phenotype, or SASP.  Senescent astrocytes and these toxins have been linked to PD.

 

What can be done to prevent and to treat Parkinson’s Disease?

Returning to the theme at the top of this page, I ask what options can people try to prevent PD or to slow its progression.

  • Selegiline (aka deprenyl, or Emsam) was a standard treatment for PD in the 1980s.  It has since fallen out of favor because of inconsistent results, but I think it deserves consideration and personal experimentation, especially since there are no outstanding alternatives.  Selegiline acts in two ways, addressing both the symptom and cause of PD.  Its primary action is an MAO-B inhibitor, which slows the chemical breakdown dopamine, so that the existing dopamine remains available longer*.  Secondarily, Selegiline is neuroprotective.

The main reason I am enthusiastic about Selegiline is because of its potential as a life extension drug.  Selegiline is on the short list of drugs that have succeeded in extending life span of rodents.  [my blog in the subject from 2 years ago]

  • Stem cell therapies are working well for some patients, and new experiments are likely to make the treatment more effective for more people.
  • Glutathione (standard abbreviation=GSH) is the only one of the body’s natural anti-oxidants that I believe has anti-aging potential.  Levels decline with age.  GSH depletion is both a cause and an effect of the loss of neurons in the SN [ref, ref].

GSH is a short protein molecule, a tripeptide.  It does not survive digestion in the stomach, but the molecule is small enough that with finesse it can be delivered orally.  There are new products with liposomal encapsulated GSH that purport to survive the stomach so that more GSH is delivered to the bloodstream.  GSH can also be absorbed in a nasal spray.  A more traditional product is to ingest N-Acetyl Cysteine (NAC) which is a precursor to GSH.

I have a friend, a vibrant 86-year-old MD who tells me he has a Parkinson’s tremor which is well managed and controlled with liposomal glutathione.  One small study of intravenous GSH for Parkinson’s showed inconsistent benefits that were not statistically significant overall, but might be interpreted as promising for a larger study.

  • There is anecdotal evidence for benefits for PD from telomerase therapy (cycloastragenol, TA65, Product B, etc).  No study has been done.  Here is a video from Ed Park.
  • Rapamycin is a powerful anti-aging drug with powerful side effects.  It has been effective in vitro and in preliminary animal trials against Parkinson’s.  It is probably a powerful neuroprotector, and has been proposed for trials delaying progression of PD.
  • Not to harp on the issue, but intermittent fasting and caloric restriction are powerfully neuroprotective.  This article from Johns Hopkins Med School reviews the evidence.

Researchers at the National Institute on Ageing in Baltimore said they had found evidence which shows that periods of stopping virtually all food intake for one or two days a week could protect the brain against some of the worst effects of Alzheimer’s, Parkinson’s and other ailments.

“Reducing your calorie intake could help your brain, but doing so by cutting your intake of food is not likely to be the best method of triggering this protection. It is likely to be better to go on intermittent bouts of fasting, in which you eat hardly anything at all, and then have periods when you eat as much as you want,” said Professor Mark Mattson, head of the institute’s laboratory of neurosciences.

Cutting daily food intake to around 500 calories – which amounts to little more than a few vegetables and some tea – for two days out of seven had clear beneficial effects in their studies, claimed Mattson, who is also professor of neuroscience at the Johns Hopkins University School of Medicine in Baltimore.

…the growth of neurones in the brain could be affected by reduced energy intakes. Amounts of two cellular messaging chemicals are boosted when calorie intake is sharply reduced, said Mattson. These chemical messengers play an important role in boosting the growth of neurones in the brain, a process that would counteract the impact of Alzheimer’s and Parkinson’s. [The Guardian]

Experimenting on yourself–the one-person trial is the only one that matters

If you have Parkinson’s Disease or Parkinsonism or early Parkinson’s symptoms, then each one of the above suggestions offers some small chance of improving your condition.  Start by keeping a daily diary of symptoms, a baseline of at least two weeks.  Then try the above suggestions, one at a time.  Continue the diary so you can look back and determine what works and what doesn’t.  If you believe you have found a benefit, go off the treatment for a week, then back on, to see if your diary reflects a response to the treatment, or if it was just a fluke.

Don’t give up.  It is unlikely that any given treatment will work for you, but it is likely that patience and persistence and controlled experimentation will be rewarded with something that helps.

 

————

* Dopamine, like all neurotransmitters and many other hormones, is continually being manufactured and simultaneously destroyed by the body.  The body regulates the amount of dopamine from moment to moment by adjusting both the rate of production and the rate of breakdown.

37 thoughts on “Can anything be done about Parkinson’s Disease?

  1. Great article as always. I wish you publish your take on statins, cholesterol, atherosclerosis and CV diseases in general.

  2. Average age of onset for PD age 62 years old
    Male to female ratio 1.5 to 1….

    what might this suggest? not enough progesterone..

    progestero0ne is most neuroprotective substance known to man….and women’s high levels are what allows them to recover from brain injuries much easier and more quickly than men..

    Women have a lifetime of higher progesterone levels than men…Until menopause when it crashes to almost 0.

    I bet if one looks into it….after age 60 the sex ratio of male to female PD patients drops to 1:1
    just as occurs in ALS patients….before menopause men get ALS 4X more than women..but it reverts to 1:1 after age of menopause in women….the commonality? lack of progesterone.
    Melatonin might help PD as it causes you to produce more progesterone.

    Finally a recent ALS mouse study confirms the progesteorne ALS link- progesteorne injections of the right dose..extended ALS mouse lifspan the human equivalent of 17 years where most ALS patients die in 2 to 4 yyears after diagnosis..-

    the study:Neurobiol Dis. 2013 Nov;59:80-5. doi: 10.1016/j.nbd.2013.07.011. Epub 2013 Jul 26.
    Autophagy activation and neuroprotection by progesterone in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis.
    Kim J1, Kim TY, Cho KS, Kim HN, Koh JY.

  3. Thank you for the excellent article.
    Loss of neurons in Substantia Nigra is the cause of Parkinson’s disease. But, what is the cause of this loss of neurons?
    Many PD patients also have digestive issues. As some of the recent research suggests, could the problems in the gut be the cause of this?
    For example, when the balance of the gut microbiome is lost, could the resulting digestive issues be impacting nervous system through the gut brain connection via vagus nerve?

  4. What can I say other than Thank you and keep on feeding us valuable info on neurodegenerative diseases.
    Thank you Josh, Jeff and Ramana!
    God bless you all

  5. Caffeine and nicotine may be helpful.
    “Both retrospective and prospective epidemiological studies have consistently demonstrated an inverse association between cigarette smoking and PD…Nicotine has been shown in animals to stimulate the release of dopamine in the striatum, and to preserve nigral neurons and striatal dopamine levels in laboratory animals with lesioned nigrostriatal pathways. Coffee and caffeine consumption have also been shown in epidemiological studies to be inversely related to PD risk.”

    http://www.ncbi.nlm.nih.gov/pubmed/11772120

    • Of course, the difference between coffee and cigarettes is that modest intake of coffee is associated with a slight decrease in overall mortality, whereas cigarettes are associated with a large increase in overall mortality.

  6. You may be interested in reading “Preventing Parkinson’s: How to Cut Your Risk by Strengthening your Multiple Shields” (available on Amazon). It is based on a comprehensive literature review of over 10,000 peer-reviewed scientific articles. The book details steps that people can immediately take to lower their risk of developing Parkinson’s.

    • Dr Weinstock – you have investigated this subject far more deeply than I have. Can you comment on anything I might gotten wrong in this brief column, or any misplaced emphasis?
      Thanks…
      – Josh

  7. Dear Josh,

    I think your article is excellent, but I would like to emphasize the following:
    1. Parkinson’s Disease is a multifactorial disease, often years, and sometimes decades, in the making;
    2. Recent research shows that on a molecular level, diabetes and Parkinson’s are closely linked;
    3. Vitamin D (from sunshine) plays a major role in preventing Parkinson’s. For example, one study showed that people with the highest levels of Vit D have a 67% reduced risk of Parkinson’s. Of course, one needs to avoid sunburns;
    4. Taking supplements may not be a good idea, as they throw off the body’s natural levels of antioxidants. Supplements have been shown to worsen diabetes, for example;
    5. A Mediterranean diet appears to be the best for preventing Parkinson’s (and many other conditions) as it is anti-inflammatory, provides high levels of antioxidants, provides fiber, and creates a pH level in the blood that inhibits alpha-synuclein;
    6. Avoid sedentary behavior, avoid obesity, avoid head trauma;
    7. More emphasis needs to be placed on prenatal and perinatal health. Dopamine-producing cells form during the first month of a pregnancy. If a pregnant woman is malnourished or exposed to toxins, the baby may be born with a lower number of those cells–thus raising the risk of Parkinson’s.

    You may want to see my blog at http://www.preventingparkinsons.com

    Sincerely
    Ben Weinstock PT, DPT

    • Ben –
      I very much appreciate your expertise. The comment about vitamin D is especially welcome. I mentioned vit D rather tentatively because there are arguments in the literature that the association between low blood levels and PD risk are not causal.
      – Josh

  8. I have had Parkinson’s for 16 years and I can’t agree more that you need to find out for yourself which meds and therapies work for you. This conclusion is reinforced by individual stories I hear at Parkinson’s support groups — meds and dosages that are effective and tolerable vary dramatically from one person to the next.

    A drug for Parkinson’s that deserves wider attention is amantadine. After encountering problems with side effects of the dopamine agonists, I fell back on levodopa and DBS surgery, but I was experiencing severe motor fluctuations between dyskinesia at peak medication and tremor when the meds wore off. Amantadine was quite effective in smoothing out these fluctuations and giving me more useable time.

    Amantadine may act by increasing noradrenergic signalling from the locus coeruleus (LC) to dopaminergic neurons in the substantia nigra (SN). LC noradrenergic neurons are depleted in PD, and noradrenergic signalling is neuroprotective to the SN in certain animal models of PD.

    Dave Ring

  9. I developed Parkinsonism shortly after a pesticide treatment in my home. Emory University recently published a study that shows a magnified risk of Parkinson’s disease for people who carry a certain gene when exposed to the common household insecticides called Pyrethroids. I am certain these pesticides triggered my condition.

  10. You forgot to mention Cannabis in your article. Cannabis helps with the rigidity, pain, depression and sleep issues. At the cellular level it reduces inflammation. According to US Patents the Department of Health and Human Services the cannibinoid CBD is both an anti-inflammatory and a neuroprotectant.

  11. Josh,

    Can you comment on the recent article on the internet regarding the Malaria drugs Chloroquine and Amodiaquine and their effect on Rats with PD? Apparently the Rats were treated with the Malaria drugs and their PD symptoms abated. The article was titled, ” Scientist Discover Potential Treatment For Parkinson’s Disease “.

    Thanks,
    Gene

    • Thank you! This looks like a great find. Here is the original article in PNAS. They did their biochemistry, and they tested it in rats and both look very promising. The drugs Chloroquine and Amodiaquine are very similar to each other and have modest side effects; (they’re not the monster malaria drug that causes nightmares).

      It is research that was completed in 2013, but review was delayed, probably because the senior author Ho Sup Yun was working in Korea. The paper was re-submitted to PNAS by a Harvard researcher, and received prompt attention.

      • Great article as well as insightful comments left by all. My mom has Parkinson’s for 3-1/2 year now, (she’s 81). I thought the disease couldn’t be diagnosed through lab testing; only through symptoms. But if scientists are using PD rats, they must be injecting them with something that causes PD which leads me to believe the diagnosis in humans can be confirmed through testing. Is there a definitive test for Parkinson’s, and if so, what is it? Thank you.

  12. Hi, do you have any observations regarding Dale Bredesen’s protocol in his paper on reversal of cognitive decline?

    http://www.impactaging.com/papers/v6/n9/full/100690.html

    I have a dog suffering from canine cognitive dysfunction, or rather I did have. I adapted this protocol somewhat for his size and species and now I get to see him relearning all the things he had forgotten. From lying on a bed howling his head off all night, sleeping all day and falling over upon walking, he made a gradual recovery. I ended up laid on the floor this morning, exhausted – from a full 20 minute tug of war game around the house with him, which I lost.

    Not bad for a dog the vet was planning to euthanise due to ‘poor quality of life’.

    Anyway the protocol is a long one with many lifestyle modifications and supplements. 9 out of the first 10 patients had a sustained recovery and they had various types of dementia, including Parkinsons.

      • Excellent news!

        I thought I would follow up and say the dog continues to improve. There appears to be nothing wrong with him now but disk disease and sarcopenia. I’m working on these. It is nice to see him just getting through doorways actually. He used to stare at the hinge side of the door waiting for it to open and he is a big dog if you have to lift him to the open side. I’m glad we’re done with all that hassle.

        Incidentally, I too have cognitive issues. I seem to be slipping into some kind of mild cognitive dysfunction – the main problem being forgetting nouns while recalling the associated adjective just fine. If I want a sweeping brush, for instance, I’ll ask for “the brushy thing” yet can’t remember the word “brush”. Inrecall what something does, but not what it is.

        Actually maybe that’s my mild Autism taking over..

        I decided to try the dogs herbs and supplements – the ones I mixed for him from the Bredesen Protocol. They seem to be working on the language issue, and I’m only on a tiny dose – maybe a tenth of what the dog gets. I have no idea which ones of the approximately 45 ingredients might be helping and life is too short to find out, so I just take them all.

        Incidentally, Dr Bredesen mentioned the leaky roof scenario and inspired by this, – this is what I tell people with these age related conditions.

        Imagine you have a house so old the roof has 50 tiny leaks causing a flood whenever it rains. Traditional pharmacology, with its ‘one pill for one ill’ and it’s reliance on synthesizing then patenting just one ingredient from a herb – plugs one hole (removes plaques, downregulates inflammation or encourages differentiation into a nerve cell phenotype etc.) This ingredient might do well in a test tube but when given to real patients the house still floods. There are 49 other holes! The drug is labelled a failure and the search continues for the next miracle.

        But it wasn’t a failure really. It did plug the hole. Now you plug the 49 others.

  13. A bit off topic but encouraging about a neurological disorder…

    My 81 year old father has had Benign paroxysmal positional vertigo (BPPV) for 5 or 6 years. There is no known cure and its debilitating, leaving one spinning and unable to function for hours, even days. He’s tried various things, including Epley maneuvers. Once he increased his Vitamin D3 level, his BPPV episodes declined to about 2 to 3 per month and unable to function… He also has one eye that shifts direction rapidly from time to time and results in dizziness. Not sure what that’s called.

    From time to time over the years, I have done google scholar searches for a cure. About 2 months ago, I found the following study from 2014.

    Vestibular rehabilitation ameliorates chronic dizziness through the SIRT1 axis
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941041/

    We immediately ordered a good quality Resveratrol product because Resveratrol increases SIRT1. I can’t recall which Resveratrol product we ordered.

    He began taking it about 7 weeks ago now. He hasn’t had a BPPV episode since he began taking it and I’ve noticed lately that his attitude and energy have very dramatically improved since then too. He’s going to increase the Resveratrol dose to see what happens. He was up on a ladder in the garage a few days ago fixing the auto garage door system… The rapid eye symptoms have continued but their effect has been much less negative.

    The exponential increases in knowledge we are experiencing are worth keeping up with for the life saving and life enhancing implications they provide!

  14. GAIM technology has shown very good progress in removing various plaque types. Michael J Fox foundation have funded development of this since 2011 and all signs are very good, it removes various plaques and amyloidosis too by targeting a common link, mis-folded proteins. Some plaque treated has seen a 40% reduction in tests.

    http://neurophage.com/science/protein-misfolding-diseases/

    NPT088 is their new candidate based on their older version
    https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1245

    NPT001 is the previous version which was good but improvement has been made
    https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=884

    Can something be done about PD, ALS, AD and similar conditions? Yes and GAIM seems to be a good contender. I checked with a friend who works with Alzheimer’s at UCLA and he says the research behind this is legit and MJF is faster than most foundations on research. GAIM is a very interesting indeed.

  15. Hi Josh,
    Another high quality blog by you…many thanks. I enjoy reading them.
    As another contributor wrote; PD is multi-factorial. What works in one person may not work in another.
    However, in at least some cases, neuronal death in the substantia nira is due to metal-catalysed free-radical (FR) production. The radicals react with Met residues in proteins. When this happens to enzymes such as catalase and S-Metionine Reductase, a positive feedback loop of FR destruction follows.
    One possible solution is to supplement with a sacrificial Met analogue.
    For example: S-Methyl-L-Cysteine. This soaks up the FR’s, sparing the Met at critical sites.
    Interestingly, SMLC is found naturally in the “Allium” family of vegetables…garlic, onion, etc.
    It is quite harmless and available in pure form from scientific suppliers.

    Cheers,

    “Dr Tom”

  16. I’ve been doing GSH nasal spray and liposomal GSH for 2 months. My GSH went from below the normal range to the very top of the high normal range. For parkinsons should I get it higher than the top of the normal range?

    Thanks

  17. I was diagnosed of Parkinson’s disease in June 2013. I was given medications like levodopa to slow down the progress of the disease. I suffered from this disease till i read online about a herbal doctor from Johannesburg, South Africa, who have herbal medicines to cure all kinds of diseases including Parkinson’s disease. We contacted this herbal doctor via his email and bought the Parkinson’s disease herbal medicine from him. He sent it to me through courier service and i received it within 7 days. I used the herbal medicine as prescribed and was totally cured of parkinson’s disease within 3 weeks of usage, all thanks to Dr Ejiro Mapipa. Contact him via his email, ejiroherbalcure(at)gmail(dot)com or call his mobile number on +27617403481 Goodluck.

    Note: This comment may not have really been from Kathy Rafieullah. Her gmail address doesn’t answer, and elsewhere the same person advertises for the same doctor, claiming a cure for heart disease derived from 23 years of smoking. – JJM

    • Hello Kathy

      Great news! Do you know what kind of herbs they were?? I would like to look at the chemical structure of their active ingredients

      thanks

  18. I have suffered parkinson’s disease since 2014 my symptoms were mainly tremor, shaking and rigid muscles, I was given levodopa and other medications to slow down the progress of the disease. I suffered from this disease till my wife’s co-worker told my wife about a herbal clinic from Johannesburg (Ejiro herbal clinic) who sell herbal medicine to cure all kind of disease including Parkinson’s disease. We contacted this herbal clinic via their email and purchased the parkinson’s disease herbal medicine we received the herbal medicine within 7 days, I started using this herbal medicine and gradually my condition improved till i was totally cured of parkinson’s disease. All thanks to Ejiro herbal clinic, Contact Ejiro herbal clinic via their email ejiroherbalclinic(at)gmail(dot)com or call +27617403481

  19. My grandfather is suffering from Parkinson’s disease. One year before his symptoms was going worse and was affecting his memory adversely. One of my friends suggested me to send him to boxing classes. I sent him to rock steady boxing classes of Kansas City. After that, I saw hard to believe improvements in his Parkinson’s symptoms. I would recommend going rock steady boxing classes at Kansas City to people suffering from Parkinson’s disease.

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