Some more good news I hope

MJFF have recently posted an article highlighting significant progress involving research into the alpha synuclein protein.

Once again, I believe that any new PD drug which might result from this research is still some years away.

michaeljfox.org/foundation/...

18 Replies

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  • M13 is now in clinical trial. It should be soon.hope for us Alzheimer's ALS and other s

  • Thanks for the good news kept me posted đź‘Ť

  • I am glad you posted this article and alpha synculein is one of the major

    targets in creating an effective therapy for Parkinson's disease. As you noted, a drug may not be coming any time soon and it takes about 10-14 years for American drug development to occur.

    I often write about vitamins, minerals, amino acids and herbs for PD so let's look at

    a sample of supplements which have been shown to effect alpha synuclein.

    NAC

    Oral N-Acetyl-Cysteine Attenuates Loss of Dopaminergic Terminals in α-Synuclein

    Overexpressing Mice

    journals.plos.org/plosone/a...

    NAC is a known quantity on this website:

    healthunlocked.com/parkinso...

    The downside of NAC is:

    N-acetylcysteine (NAC): This Common Antioxidant Supplement Could Cause You Loads of Trouble

    "NAC can form a red blood cell-derived molecule called nitrosothiol that fools your body into thinking there’s an oxygen shortage, which can lead to pulmonary arterial hypertension (PAH)."

    articles.mercola.com/sites/... antioxidant-supplement-could-cause-you-loads-of-

    What is the easiest way to limit the possible negative effect of NAC on your heart?

    Take CoQ10 everyday:

    CoQ10 Shows Potential Benefit for Pulmonary Arterial Hypertension Patients

    consultqd.clevelandclinic.o...

    Components of green tea have often been spotlighted for their positive effects on PD

    but black tea is the 'Rodney Dangerfield' of teas - it get's no respect. I think black tea extract is as important as green tea components (if not more) and in several studies showing BTE or its components to be a possible therapy to counteract alpha synuclein aggregation:

    Black tea theaflavins inhibit formation of toxic amyloid-β and α-synuclein fibrils.

    ncbi.nlm.nih.gov/pubmed/220...

    Swanson has an inexpensive black tea extract that I have been using for years:

    swansonvitamins.com/swanson...

    Magnesium:

    Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein.

    ncbi.nlm.nih.gov/pubmed/118...

    My preferred form of magnesium is magnesium threonate because it passes the blood brain barrier and is absorbed better (by 15%) than other forms of Mg.

    Inhibition and disaggregation of α-synuclein oligomers by natural polyphenolic compounds

    "It was found that Baic, EGCG, Myr, NDGA and BTE significantly disrupted both types of oligomers to <20% of their initial aggregated state."

    sciencedirect.com/science/a...

    The above article is long and boring with much techno babble so I will highlight the 'natural phenolic compounds' they mentioned in the above quote:

    Baicalein is a component of the herb Scutellaria Baicalensis more commonly known as Skullcap. Skullcap is one of the main Chinese medicinal herbs and it has many properties including another neuroprotective component: baicalin.

    Baicalein can only be purchased in the herb Skullcap but what about baicalin and PD?

    google.com/webhp?sourceid=c...

    I could not find any evidense that baicalin has an effect on alpha synuclein but, besides being a possible therapy for PD, it is a great anxiolytic agent and good for

    osteo-arthritis. The downside to baicalin is it can cause liver toxicity. The prevent this effect I combine it with L-theanine on a 1 to 1 ratio at bedtime (200 mg of each) to help me sleep and improve my joint condition. In my opinion the amino acid L-theanine is one of the safest and best therapies for PD and works on so many levels it is amazing.

    In an acetominophen model of liver damage theanine reverse the toxicity of this NSAID:

    agris.fao.org/agris-search/...

    NAC is also liver protective and is the go to treatment at hospitals for

    acetaminophen OD.

    The black tea extract used in this study was of 80% concentration and the above

    Swanson supplement was 20% theaflavins. It is ok to take more of this supplement at high doses but I prefer to cross compliment supplements with similar effect.

    Black tea extract, at higher doses, has been used by athletes:

    The effects of theaflavin-enriched black tea extract on muscle soreness, oxidative stress,

    inflammation, and endocrine responses to acute anaerobic interval training: a randomized,

    double-blind, crossover study

    "Subjects consumed the BTE (1,760 mg BTE·d-1) or placebo (PLA) for 9 days."

    ncbi.nlm.nih.gov/pmc/articl...

    EGCG is the best known catechin from green tea (it exists in trace elements in black tea)

    and I use it as a decarboxylase inhibitor when taking mucuna pruriens levodopa.

    EGCG: Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation:

    A Potential Agent for Parkinson's Disease.

    ncbi.nlm.nih.gov/pubmed/273...

    I have noted the possible dangers of large dose EGCG but take many other liver protective

    supplements. I noted this fact in this thread:

    healthunlocked.com/parkinso...

    One of the ways I reduce/eliminate the risk of EGCG is to take quercetin with it.

    Quercetin is a COMT inhibitor, like entacapone, and also is a prospective therapy to counteract alpha synuclein toxicity and prevent liver damage.

    Really, anyone on sinemet should think about taking quercetin with it because you thus

    create a combination very much like Stalevo = levodopa + carbidopa + COMT inhibitor

    Quercetin/liver:

    Oxidized quercetin inhibits α-synuclein fibrillization.

    ncbi.nlm.nih.gov/pubmed/232...

    Quercetin/liver: ncbi.nlm.nih.gov/pmc/articl...

    Quercetin COMT activity:

    ncbi.nlm.nih.gov/pubmed/127...

    "The results of the present study strongly suggest that quercetin could serve as an effective

    adjunct to L-dopa therapy in Parkinson's disease."

    Do you have anxiety? Chamomile is a common remedy and has been shown to be neuroprotective

    in PD models. A component of chamomile is apigenin and most chamomile supplement have

    standardized 1.2% apigenin and the supplement is equivalent to drinking a cup of

    chamomile tea.

    A separate article:

    researchgate.net/publicatio...'s_disease about apigenin, AS and PD:

    I am running out of steam and I would be remiss to mention my favorite blood brain barrier

    penetrating supplement: the combination of acetyl l carnitine and alpha lipoic acid.

    Combined R-alpha-lipoic acid and acetyl-L-carnitine exerts efficient preventative

    effects in a cellular model of Parkinson's disease.

    "We demonstrated that 4-week pretreatment with LA and/or ALC effectively protected SK-N-MC human neuroblastoma cells against rotenone-induced mitochondrial dysfunction, oxidative

    damage and accumulation of alpha-synuclein and ubiquitin. Most notably, we found that when combined, LA and ALC worked at 100-1000-fold lower concentrations than they did individually."

    ncbi.nlm.nih.gov/pubmed/204...

    A bit of an epic here but it is good to know that supplements for alph synuclein toxicity already

    exist and are readily available. Mind you, this is a beginning list of supplements and a not all inclusive one.

    Have a good Sunday.

    Rich

  • Thanks for your mention of the downside of NAC. I just got in a kilogram of it and started taking 10g/day based the high-dose NAC regimens reported to help PD. Will put that on hold for now pending further research - PAH is really bad news - do not want to end up with that. Here is the link to the research Mercola referenced:

    ncbi.nlm.nih.gov/pmc/articl...

  • From researching NAC I have concluded it is unsafe only at high dose. Most clinical trials use 1800 mg/day (or more) and I have taken from 1200 - 1800 mg/day for years with no problems. I think it mandatory to take some form of coq10 with NAC. Considering the potential upside of coq10 and the absence of side effects for PWP, I think it is a 'no brainer'. It may be an opportunity to see if 2 mitochondrial agents can improve your health. Standard ubiquinone may be a place to start at 600 mg/day in 3 divided doses. This may be a something good in disguise.

    PS. I found this article which emphasizes the need for PWP to take supplements which stimulate mitochondrial function:

    Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD.

    ncbi.nlm.nih.gov/pubmed/213...

  • Found a study of NAC in cystic fibrosis patients where they established safety of NAC with respect to PAH at the 2700 mg/day level. They were aware of the mouse study and specifically looked for conversion to SNOAC, among other things, which is what caused trouble for the mice:

    "The Stanford cohort of 16 subjects served as an initial safety

    cohort to evaluate if long-term treatment with NAC was

    associated with the development of PH in subjects with CF.

    There was no evidence for the development of PH in these

    subjects by the following biomarker and clinical measurements:

    levels of plasma NAC, SNOAC, HIF-1α, VEGF, bFGF,

    cardiac echocardiogram and diffusion capacity for carbon

    monoxide."

    sci-hub.cc/10.1016/j.jcf.20...

  • I looked at the mouse study and the doses of NAC were huge - don't have the stats in front of me. 2700 mg/day sounds like a good daily dose to shoot for.

  • The mousies received NAC as 1% solution in drinking water. Typical mouse water intake around 7ml/30g body weight

    (see ncbi.nlm.nih.gov/pmc/articl...

    which amounts to over 2 g/kg of NAC, so yeah is huge. The recent study that gave humans 6g/day amounts to 50-100mg/kg. So the mice got over 20x as much.

  • Thanks for confirming my mental calculations. I read the article and did some basic math and knew they were heavy handed in the study. Given this fact I think it is safe to take a good daily dose of NAC - unless you start taking a couple pounds of it a day (or grow a tail and whiskers).

    In my reply to jeffreyn (below) I noted that a cluster of supplements work very well together.

    On one study: acetyl l carnitine, alpha lipoic acid with coq10. In another NAC and alpha lipoic acid work well together. For future use it might be interesting to take all of the above - which I do. My idea is to use complimentary supplements so that large doses can be avoided and efficacy is improved.

    Best of luck with the NAC.

  • silvestrov,

    Thanks for the reply, and all the links.

    Jeff

  • Jeff,

    It is my pleasure in posting the info and I hope it helps people. What I am suggesting with the above information is to combine multiple mitochondrial enhancing supplements that have synergy to make the 'whole' - the totality of the therapy, greater than the sum of its parts (individual supplements taken in isolation).

    Let me give you an example.

    Management of the aging risk factor for Parkinson's disease.

    "The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins."

    ncbi.nlm.nih.gov/pubmed/242...

    In a previous post I noted that alpha lipoic acid and acetyl l carnitine, when combined, "worked at 100-1000-fold lower concentrations than they did individually. "

    ncbi.nlm.nih.gov/pubmed/204...

    So you get great bang for the buck when ALA and ALC are combined. I mentioned NAC in the above thread and does it have any synergy with any of the above supplements?

    Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts

    "Furthermore, we observed that the protective effect of LA and NAC was more pronounced when both agents were present simultaneously."

    researchgate.net/publicatio...

    So ALA and ALC have synergy (with coq10) and ALA and NAC have synergy. NAC has potential side effects which are countered by Coq10.

    __________________________________________________________________________

    Midlife Migraines Linked to Increased Parkinson’s Risk

    medicalnewstoday.com/articl...

    Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial

    "Mitochondrial dysfunction is associated with migraine. Riboflavin, magnesium and coenzyme Q10 play an important role in the production of energy in the mitochondria."

    ncbi.nlm.nih.gov/pmc/articl...

    Dolovent: dolovent.com/about.aspx

    I have looked at the above migraine supplement and you can do better by purchasing separate (superior) components than what the pill offers. The pill has magnesium oxide, the worst form of magnesium to take because it has poor bioavailability (only 4%). Stick with magnesium threonate.

    Riboflavin:

    High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients

    scielo.br/scielo.php?script...

    The riboflavin study has patients taking 30 mg of riboflavin every 8 hours and it only comes in 100 mg doses. Yes there are some multi-vitamins which have nearly this dose but multivitamins most often do not use the best forms of their respective vitamins.

    riboflavin-5-phosphate is the bioavailable form of riboflavin as is more potent that taking standard riboflavin.

    Ubiquinol (reduced CoQ10):

    ncbi.nlm.nih.gov/pubmed/260...

    Magnesium:

    Intracellular magnesium level determines cell viability in the MPP+ model of Parkinson's disease

    sciencedirect.com/science/a...

    __________________________________________________________________________

    There are other supplements that can be 'stacked' to use an old weightlifting term to created a combined effect.

    Other supplements which can help mitochondrial dysfunction and work well with those listed: NADH, and if you are poor like myself, use nicotinamide/niacinamide, vitamin K, folate (methyltetrahydrofolic acid) and if you take folate, you should take methylcobalamin. Those 2 B vitamins are linked at the hip.

    __________________________________________________________________________

    Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD.

    ncbi.nlm.nih.gov/pubmed/213...

    Rich

  • Rich, your suggestion to combine multiple mitochondrial enhancing supplements reminded me of the article in the August, 2016, Smithsonian magazine titled ANATOMY OF A CURE: DR. PINKEL'S MIRACLE. It's the story of St Judes and Dr Pinkel's approach to defeating childhood leukemia, but also about the character of Dr. Pinkel.

  • Many thanks for your kind words. When I write about combining mitochondrial supplements I am just pointing out the obvious. There are numerous....hundreds of....studies on the subject and there are even articles which actually suggest using such an approach:

    Mitochondrial therapy for Parkinson’s disease: Neuroprotective pharmaconutrition may be disease-modifying

    ncbi.nlm.nih.gov/pmc/articl...

    The article concentrates on the combination of coq10 and creatine. Yes this combination is good for PD:

    The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson's disease.

    "Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function."

    ncbi.nlm.nih.gov/pubmed/257...

    Why did I leave creatine out of the supplements I mentioned above?

    Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine.

    ncbi.nlm.nih.gov/pubmed/263...

    Caffeine is such an accepted therapy for PD in the form of tea or coffee, recommending creatine would be dangerous because everybody likes their caffeine fix - myself included.

    Caffeine and creatine is a hot button issue on weight lifting forums. If you want to learn about amino acids, vitamins, herbs.....go to a gym and skip your doctor. You will get better advice at the gym.

    The debate: bodybuilding.com/fun/berard...

    I will research Dr. Don Pinkel later in the week when I have a little more time.

    Have a good evening and best wishes. I am ready to chill out and hit the sack. I had 2 hours of sleep last night and am surprisingly alert (all things considered).

    Rich

  • Sometimes I wonder if perhaps you might be Dr. Bruce Ames masquerading as Silvestrov/Rich, but for sure you are an angel here on earth. Thank you for all the info you so generously provide us. I give thanks each day.

  • It is my pleasure to post the information I have amassed through the years. I do so in the hopes it helps PWP. I am not Dr. Bruce Ames, lol, just an over educated/underpaid artist who is an OCD researcher.

    I am about to finish another post related to the large one above. It is about combining synergistic supplements which can help challenge mitochondrial dysfunction. In my opinion, if MD can be improved, PWP will be able to use less standard Parkinson's medications and suffer less side effects.

    The post will be directly below jeffreyn's response (I just posted it)...

  • Wow!!

  • Thanks. Thanks Silvestrov!

  • Jeffreyn, I would love to think so. Here's a little info highlighted from MJFF:

    The drug — aducanumab (BIIB037) — showed safety and positive impact not only on clinical symptoms but also on brain imaging scans.

    Alzheimer’s, like Parkinson’s, is a disease of protein clumps. In Alzheimer’s the protein amyloid-beta aggregates into what scientists call plaques. In Parkinson’s disease (PD), alpha-synuclein protein clumps to form Lewy bodies. Researchers believe these plaques and Lewy bodies harm brain cells. Scientists are currently testing two antibody approaches against alpha-synuclein in clinical trials to slow Parkinson’s progression. The positive results from this Alzheimer’s study are a boost that this therapeutic strategy shows real promise.

    For those interested in a Clinical Trial: foxtrialfinder.michaeljfox....

    A Phase 1 Randomized, Double-Blinded, Placebo-Controlled Single-Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB054 in Healthy Subjects and Subjects With Early Parkinson's Disease

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