Dr Alok Sharma, India, stem cell injections to spinal fluid

www.stemcellspublications.com/index.html

can’t use donor stem cells when injecting to spinal fluid, because it has a preservative or something

Using own stem cells generated from patient fat tissue or bone merrow

they treat several neurological conditions, but does not mention PD, it’ll sent them a question

Dr Alok also points that some countries in Asia including China and India are ahead of the US in stem cell research and applications. The reason is president Bush banned stem cell due to ethical concerns Obama resumed stem cell research and applications but some gap still exist

MSC Stem cell testimonials

Looking at testimonials of elite athletes treated with stem cell injections

Testimonials from Stem cell institute in panama, including Joe Rogan and Tony robins >>

Dr Yoni Whitten tried stem cells

also, has Ebook

Stem Cell Mistakes Ebook

CPI clinic in Mexico

Has some testimonies here
www.youtube.com/@CellularPerformanceInstitute/videos
very happy client here

UFC competitor talk with Joe Rogan about his treatment at CPI

Another UFC guy treated at CPI, talks to Joe Rogan

UFC guy talks to Joe Rogan about his stem cell treatments at Bioxcellerator in Colombia

Bodybuilder did intense stem cell therapy with amazing results

UFC champion and current belt holder, Sean O’Malley, visit the clinic to treat his knee and other issues, treatment comprise of stem cell. HBOT, PRP injections, the visit has a lot of PR

MSC stem cells for Pennies improvement

Ross Edgley swam around UK, and then got stem cells for many joints

Dr Mark Hyman got a similar treatment

Ben Greenfield repeated the treatment 3 more times, says he feel like 18 years old. This is the most expensive treatment, as it targets many joints and it’s done in the US. Due to US regulation, growing stem cells culture in the lab is not allowed, all stem cells are from the client or from the donor, this also makes the treatment expansive, growing stem cell in a lab for many generations reduce costs but has negative side effects. growing stem cells for up to 2 generations or so is OK (if I remember correctly from lecture by Dr Rirden from the Panama clinic.

The Clinic docereclinics.com, is going to offer an affordable version of the treatment soon.

Reduce dopamine in the cell to prevent longterm damage

The researcher make assment of the dopamine level in the cell, and says its to hi if supplementing with dopa

he notes that level of dopaminme inside the cell was not measured so far, and was not considered a thing

he attempts to repurpose drug that that will help managing dopamine level in the cell,

the drug is Metyrpsine –

Metyrosine is a tyrosine 3-monooxygenase inhibitor

looking to start phase 2 trial, looking for , money

go.drugbank.com/drugs/DB00765

The parkinson’s epidemic, TCE, Paraquat

Parkinson’s disease was a rare disease 200 years ago, and is now  common

The number of PD cases doubled in the last 20 years

Young onset PD is a recent phenomena

So, environmental changes,   and industrialization, may play a role

TCE – has many uses, produced in large amounts, cause PD, may be a leading cause of the rise in PD cases

Paraquat – weed killer, heavily used, cause PD

Lecture by one of the writers of “Ending Parkinson deases”

Below, Nurologist and author David Perelmuter interview Dr. Ray Dorsey

The Stanford/Dr Tass, Vibration glove treatment for PD

Introduction

discussuion on reddit

Any thoughts on the Vibration Gloves?
by u/cicla in Parkinsons

few notes

according to the video, the glove treatment is very affective, some results show after 1 day, at least for some people the effect of symptom reduction is amazing, this suggest that the cause of symptoms was not massive dopaminergic cell death but instead, dysregulation of dopaminergic cells that disrupted dopamine production

the developer of the treatment looks at the problem (PD..dopaminergic cells not releasing dopamine) from a systems perspective, and develop a way to reset existing dysregulation (or more specifically disrupt synchronization – a process in which one cell type sync other cell types, to behave like it )

it’s a way to reboot/restart to prevent accumulation of processing errors. actually it’s more targeted then a general restart. Maybe Electroconvulsive therapy, more suitable “reset” option ..some evidence >>

for example, you can solve most Windows errors simply by rebooting it. If you had to dive into some window issue (e.g. computer hanging, slow, printer messed, weird error message, apps installed don’t work..) well, not a realistic goal

so, when looking at parkinson’s from a system approach perspective, a good start would be to find a way to reboot you system

this will not solve all issues, e.g. if you got PD from exposure to a toxin rebooting your system will not to much

same with windows, if you got a computer virus and it’s causing issue. a reboot might not be sufficient

but in case a particular sequence of events is not handled well by the system and cause an error situation with lasting effect.. reboot might help as long as you don’t repeat that sequence

in my case, many years ago, I lost my sense of smell, at the time, I theorized that my intuition took over some of the neurons dedicated to the processing of smell, intuition was one of my mostly used “modules” ( see Meir Briges type classifier, this personality type classification is based on identifying the main modules used’ e.g thinking/sensing/feeling/intuiting)

clinical trials >>

Tass lab >>

MTOR activation may reduce dophamin/l-dopa concentration in the brain

according to chatgpt, MTOR activation may reduce brain concentration of dopamine/l-dopa, some suggested mechanism of action is mentioned below

does MTOR affect l-dopa transfer in the BBB?
ChatGPT
The mammalian target of rapamycin (mTOR) is a protein kinase that regulates various cellular processes, including protein synthesis, cell growth, and autophagy. Meanwhile, levodopa (L-DOPA) is a medication commonly used to treat Parkinson’s disease. It is converted to dopamine in the brain, where it acts as a neurotransmitter.

There is some evidence suggesting that mTOR activation in the brain may influence the transport of L-DOPA across the blood-brain barrier (BBB). In a study published in the journal Nature, researchers found that mTOR inhibition with rapamycin increased the transport of L-DOPA across the BBB in mice, suggesting that mTOR may play a role in regulating the transport of L-DOPA into the brain (Carvey et al., 2011).

However, it should be noted that the exact mechanism by which mTOR affects L-DOPA transfer in the BBB is not yet fully understood, and further research is needed to elucidate this relationship. Additionally, the findings from animal studies may not necessarily apply to humans, and clinical studies are needed to determine the relevance of these findings to human disease.

User
how MTOR activation influence the transport pf l-dopa accross the blood brain barier?
ChatGPT
The exact mechanism by which mTOR activation influences the transport of L-DOPA across the blood-brain barrier (BBB) is not fully understood, but there are several hypotheses.

One possible mechanism is that mTOR activation may increase the expression and activity of efflux transporters in the BBB, which can decrease the uptake of L-DOPA into the brain. Efflux transporters are proteins that pump substances out of the brain and back into the bloodstream, and they play a critical role in regulating the transport of drugs and other substances across the BBB. Studies have shown that mTOR activation can upregulate the expression and activity of efflux transporters such as P-glycoprotein (P-gp), which can limit the uptake of L-DOPA into the brain (Bickel et al., 2015; Tai et al., 2015).

Another possible mechanism is that mTOR activation may increase the activity of enzymes that metabolize L-DOPA in the brain, which can decrease the availability of dopamine and limit the therapeutic efficacy of L-DOPA. For example, mTOR activation has been shown to increase the expression and activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes dopamine and L-DOPA (Jiang et al., 2016).

It’s worth noting that the relationship between mTOR activation and L-DOPA transport across the BBB is complex and may depend on various factors such as the dose and duration of treatment with mTOR inhibitors. Further research is needed to fully understand the mechanisms underlying this relationship.

User
so what trigger activation of MTOR
ChatGPT
mTOR activation is triggered by a variety of cellular signals, including growth factors, nutrients, energy status, and stress.

One of the primary activators of mTOR is insulin-like growth factor 1 (IGF-1), a hormone that is released in response to growth hormone and plays a key role in regulating growth and development. Other growth factors, such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), can also activate mTOR.

Nutrients such as amino acids, glucose, and lipids can also stimulate mTOR activation. In particular, the amino acid leucine is a potent activator of mTOR. When amino acid levels are high, mTOR is activated and stimulates protein synthesis and cell growth.

Energy status also plays a role in mTOR activation. When cellular energy levels are high, as indicated by high levels of ATP and low levels of AMP, mTOR is activated. Conversely, when energy levels are low, as indicated by low levels of ATP and high levels of AMP, mTOR is inhibited.

Finally, stress signals such as oxidative stress, DNA damage, and hypoxia can also activate mTOR. These signals can lead to the activation of downstream pathways that stimulate mTOR, promoting cell survival and adaptation to stress.

It’s worth noting that the precise mechanisms by which these signals activate mTOR are complex and not fully understood. Further research is needed to fully elucidate the pathways involved in mTOR activation.

Radical new therapy for Parkinson’s will use stem cell transplants

Lab-grown nerve cells will replace those destroyed by disease – scientists hope treatment may be available in five years

Source: Radical new therapy for Parkinson’s will use stem cell transplants

STEM-PD trial 2024, 1 year after 4 succesful transpalnts out of for, now major side effects, and 4 more transplants done with higher dose, they will monitor the outcome for 3 years

STEM-PD, a cell-replacement trial for Parkinson’s, releases latest update

PD – Reduce Alpha-synuclein level, experimental protocol

Misfolded Alpha synuclein protein accumulate into aggregates (oligomers) and damage host cell. PD patients brain cells tend to express alpha synuclein in large amounts, Alpha-synucleinis assumed to have a role in the disease process, reducing Alpha-synuclein level may prevent neuron death and delay or reverse the disease process  More information >> [20]

The goal here is to normalize Alpha-synuclein level by using a simple protocol

Some notes:

  • Evidence is limited
  • Most references to the available evidence, is to scientific articles/research
  • Some “how to” information on healthline.com also linked to aid implementation
  • The challenge – decision making under conditions of uncertainty (meaning – evidence is partial, what do you do?).
  • The solution (hopefully)  – use a collection of tools, each with limited evidence,   while probably not all work, most likely some will work

The protocol:

1 – Sweating – 3 liters/day or so, research show that Alpha-synuclein accumulate around sweat glands, it seems safe to assume that Alpha-synuclein is secreted via the sweat glands [18],  [1]

2 – Alpha-synuclein is also secreted in the urine, so you can detox by drinking a lot and using mild diuretics e.g. parsley [2]

List of natural diuretics >>

3 – Probiotics Bacillus Subtillis PXN21, “eats” Alpha-synuclein in the gut, this probiotics is in the market for a number of years, it’s probably safe Successful experiment in animal model(worms) [3].

Note: several bacteria species ( Lactobacillus and Enterococcus) interact with Levodopa ,and so , limit production of dopamine in the brain 

4 – Optimise detox at the cell level (from the cell, out),  raise glutathione level ( intravenous  or suppository glutatyon or eat the precursors e.g sulfur found in eggs and cruciferous vegetables).

Glutathione has other benefits( master detoxifier, master anti oxidant), so it’s a good idea to boost it anyway [19].

How to increase glutathione by Mark Hayman [17]

More ways to increase glutathione [4].

Note, the other direction, overexpression of Alpha synuclein cause a decrease in glutathione level [5].

5 –

Sleep issues may have an adverse effect on brain detox processes, in particular on alpha synuclein clearance [6].

Most of the brain detox is done by the Glymphatic System during sleep, give it time, 7-8 hours of sleep, don’t go to sleep to late. More information [7].

During sleep, glymphatic system activity is characterized by a 60% increase in the interstitial space and CSF flow (Jessen et al., 2015; Xie et al., 2013), and clearance of alpha-synuclein, along with other protein accumulations, from the brain (Iliff et al.,  2012[6].

6 – Improve autophagy by intermittent fasting, preferably keto-fast – meaning a ketogenic diet in a 12 hours or less, daily eating window Ketogenic diet induced autophagy [8].

7- Alpha synuclein is found in Vertebras e.g cow, pig, chicken. Those molecules are almost identical to the human Alpha-synuclein, but not 100% identical, and may have a role in creating a pathology, much like in prion infection, more information >>[9].

Consider avoiding vertebrates, especially brain, bone merrow, bone broth.

Eggs – OK, as far as I checked.

8 – Mannitol

Mannitol was shown to inhibit formation of Alpha-synuclein oligomers[10], and there are anecdotal improvement reports of PD patients.

A clinical experiment (n=36) did not show significant improvement

You can add Mannitol to your diet in the dosage used in the experiment – start with 2.5 gram 2 times a day, gradually increase to 9 grams 2 times a day.

Why use Mannitol if the experiment showed no improvement ?
If, for example, subjects have existing damage(accumulated before the experiment), but new damage build up is slowed by say 50%, that’s very good, but the subjects will not experience any improvement. Maybe after a long time, difference relative to the control group will begin to show

9 – HSP – Heat shock proteins

Heat shock proteins – are listed here as they slow down or inhibit the formation of Alpha-synuclein oligomers.

The level of HSP in the body rise in response to adverse conditions (ice bath, sauna…intense exercise)

Sulforaphane- a compound found mostly in broccoli sprouts, also increase level of HSP. Sulforaphane is available in supplement form

Sulforaphaneis also beneficial to brain health as it reduces inflammation, increase anti oxidant activity and more [13], so it’s a good idea to use it anyway.

Mannitol  also increase HSP level, this is one of  the suggested mechanisms of action that explain why it inhibits creation of Alpha-synuclein oligomers, and generally improves PD [11].

Different heat shock proteins bind α-Synuclein with distinct mechanisms and synergistically prevent its  amyloid aggregation
[12]

More information on Sulforaphane >>
[13]

HSP27 binds Alpha synuclein  >>[14]

and

Sulforaphane increase level of HSP27 >> [15]

also  Sulforaphane increase level of HSP70 >>
[16]

10 – High intensity exercise

Irisin, a hormone secreted into the blood during high endurance and aerobic exercise, reduces levels of alpha-synuclein and restores movement in mouse models of PD [22]

Clinical research showing beneficial effect of high intensity exercise in PD patients  [23]

11 – Ambroxol – an over-the-counter cough syrup

One of the major genetic risk factors believed to contribute to the development of PD is having a mutation in the gene called GBA1 (glucocerebrosidase). Unable to do its job correctly, this damaged gene leads to the build-up of unhealthy, misfolded clumps of alpha-synuclein in the brain. These clumps, called Lewy bodies, impact dopamine production and are the hallmark of PD.

A 2020 study published in JAMA Neurology, titled, “Ambroxol for the Treatment of Patients with Parkinson Disease with and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial” (Mullin et al., 2020), investigated whether an over-the-counter cough syrup, called Ambroxol, may be the key. [24]

12 – Mega dose, Vitamin B1 (Thiamine),

Vitamin B1, especially in high dose, improve PD  status according to a number of studies, one mechanism of action is reduction of Alpha-synuclein [24]

 

What to expect ?

If there is existing damage, and the protocol manage to stop/delay/reduce  further damage, e.g. by 100%,  this would be a significant achievement, but will not show as reduced symptoms (assuming n=1, meaning you tried it on yourself and you don’t have a control group etc).

A healthy person loose about 1% of its dopaminergic neurons every adult year,  this will not present symptoms as symptoms start showing when 80% or more of the dopaminergic capacity is gone

In a PD patient who started the protocol with say  15% of its dopaminergic capacity, even in the case of 100% cleanup of alpha synuclein, he will still be on 15% capacity and 14% next year, so…[21]

Not saying this to discourage, I believe the protocol worth the effort, and can by you time. I believe solutions based on gene therapy and stem cell  technology will be available soon.

Measuring Alpha-synuclein level require biopsy, we don’t have this technology available, but based on what we know from animal models, the protocol should work, at list some of it.

Besides it’s effect on Alpha-synuclein, the protocol is expected to improve brain health through several mechanisms including  reduced inflammation, normalizing heavy metals and other toxins, reduce oxidative stress, improved insulin sensitivity… So…good idea to try it anyway.

One more thing, a quote from  coacher Tony Robins –

Take Massive Action

 

What do you think ? feedback welcome, please comment below

Sign up for updates  here >>
(you will get a confirmation email)

Want to try it ?  good luck !  ( needless to say,  it’s your responsibility )

Please fill free to contact with any issue

Guy
0522-597925
guy@mashlima.com

 

Note:

This TED talk ___ suggests that misfolded alpha-synuclein aggregates are not a problem as long as normal alpha-synuclein is abundant, is this claim is correct, the above protocol  should be avoided

I collected the above set of tools, as they directly affect alpha-synuclein. Nevertheless, most those are very popular general health tools  e.g IM fasting, Keto, detox, sleep cycle compatible with circadian rhythm, Glutathione, Heat shock protein…

So, since they are popular, they seem to be safe.

[1] –

Gibbons, C. H., J. Garcia, N. Wang, L. C. Shih, and R. Freeman, 2016, The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease: Neurology, v. 87, no. 5, p. 505–512, doi:10.1212/wnl.0000000000002919.

‌‌[2] –

Giri, B., M. Seamon, A. Banerjee, S. Chauhan, S. Purohit, J. Morgan, B. Baban, and C. Wakade, 2021, Emerging urinary alpha-synuclein and miRNA biomarkers in Parkinson’s disease: Metabolic Brain Disease, v. 37, no. 6, p. 1687–1696, doi:10.1007/s11011-021-00735-2.

‌‌‌[3] –

Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation  -, 2022: <healthlinks.cc/probiotic-bacillus-subtilis-protects-against-%ce%b1-synuclein-aggregation/&gt; (accessed October 6, 2022).

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Berkheiser, K., 2018, 10 Natural Ways to Increase Your Glutathione Levels: Healthline Media: <www.healthline.com/nutrition/how-to-increase-glutathione#TOC_TITLE_HDR_4&gt; (accessed October 6, 2022).

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Perfeito, R., M. Ribeiro, and A. C. Rego, 2016, Alpha-synuclein-induced oxidative stress correlates with altered superoxide dismutase and glutathione synthesis in human neuroblastoma SH-SY5Y cells: Archives of Toxicology, v. 91, no. 3, p. 1245–1259, doi:10.1007/s00204-016-1788-6.

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Sundaram, S., R. L. Hughes, E. Peterson, E. M. Müller-Oehring, H. M. Brontë-Stewart, K. L. Poston, A. Faerman, C. Bhowmick, and T. Schulte, 2019, Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease: Neuroscience & Biobehavioral Reviews, v. 103, p. 305–315, doi:10.1016/j.neubiorev.2019.05.016.

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Raypole, C., 2020, How to “Detox” Your Brain (Hint: It’s Easier Than You Think): Healthline Media: <www.healthline.com/health/brain-detox&gt; (accessed October 6, 2022).

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Lindberg, S., 2018, Autophagy: What You Need to Know: Healthline Media: <www.healthline.com/health/autophagy#diet:~:text=In%20response%20to%20this%20restriction%2C%20your%20body%20will%20begin%20to%20start%20producing%20ketone%20bodies%20that%20have%20many%20protective%20effects.%20Khorana%20says%20studies%20suggest%20that%20ketosis%20can%20also%20cause%20starvation%2Dinduced%20autophagy%2C%20which%20has%20neuroprotective%20functions.&gt; (accessed October 6, 2022).

‌‌‌[9] –

www.nature.com/articles/s41531-017-0035-z#:~:text=Dietary%20sources%20of%20%CE%B1%2Dsynuclein&text=%CE%B1%2DSynuclein%20protein%20is%20highly,cow%2C%20and%20chicken%2C%20respectively.

‌‌[10] –

Linetsky, E., S. Abd Elhadi, M. Bauer, A. Gallant, M. Namnah, S. Weiss, D. Segal, R. Sharon, and D. Arkadir, 2022, Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson’s Disease: Frontiers in Neurology, v. 12, doi:10.3389/fneur.2021.716126.

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Linetsky, E., S. Abd Elhadi, M. Bauer, A. Gallant, M. Namnah, S. Weiss, D. Segal, R. Sharon, and D. Arkadir, 2022, Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson’s Disease: Frontiers in Neurology, v. 12, doi:10.3389/fneur.2021.716126.

‌‌‌[12] –

www.frontiersin.org/articles/10.3389/fnins.2019.01124/full#:~:text=%CE%B1%2DSynuclein%20(%CE%B1%2DSyn)%20forms,and%20different%20Hsps%20remains%20unclear.

‌‌[13] –

Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice., 2019: <www.foundmyfitness.com/news/s/emuzn7/sulforaphane_which_is_high_in_broccoli_sprouts_clears_away_brain_amyloid_plaques_and_tau_tangles_and_ameliorated_memory_defects_in_mice/comments/gsmrq4#:~:text=To%20learn%20more,jed%2Dw%2Dfahey&gt; (accessed October 6, 2022).

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Cox, D., D. R. Whiten, J. W. P. Brown, M. H. Horrocks, R. San Gil, C. M. Dobson, D. Klenerman, A. M. van Oijen, and H. Ecroyd, 2018, The small heat shock protein Hsp27 binds α-synuclein fibrils, preventing elongation and cytotoxicity: Journal of Biological Chemistry, v. 293, no. 12, p. 4486–4497, doi:10.1074/jbc.m117.813865.

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Gan, N., Y.-C. Wu, M. Brunet, C. Garrido, F.-L. Chung, C. Dai, and L. Mi, 2010, Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27: Journal of Biological Chemistry, v. 285, no. 46, p. 35528–35536, doi:10.1074/jbc.m110.152686.

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Schepici, G., P. Bramanti, and E. Mazzon, 2020, Efficacy of Sulforaphane in Neurodegenerative Diseases: International Journal of Molecular Sciences, v. 21, no. 22, p. 8637, doi:10.3390/ijms21228637.

17-

Hyman, M., 2010, What is Glutathione and How Do I Get More of It? – Dr. Mark Hyman: <drhyman.com/blog/2010/05/12/what-is-glutathione-and-how-do-i-get-more-of-it/&gt; (accessed October 9, 2022).

18-

‌Wang, N., C. H. Gibbons, J. Lafo, and R. Freeman, 2013, -Synuclein in cutaneous autonomic nerves: Neurology, v. 81, no. 18, p. 1604–1610, doi:10.1212/wnl.0b013e3182a9f449.

‌19-

Dringen, R., 2000, Metabolism and functions of glutathione in brain: Progress in Neurobiology, v. 62, no. 6, p. 649–671, doi:10.1016/s0301-0082(99)00060-x.

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Fields, C. R., N. Bengoa-Vergniory, and R. Wade-Martins, 2019, Targeting Alpha-Synuclein as a Therapy for Parkinson’s Disease: Frontiers in Molecular Neuroscience, v. 12, doi:10.3389/fnmol.2019.00299.

‌21-

Peters, R., 2006, Ageing and the brain: Postgraduate Medical Journal, v. 82, no. 964, p. 84–88, doi:10.1136/pgmj.2005.036665.

‌22-

Exercise Hormone Halts Parkinson’s Disease Symptoms

23 –

Forced exercise 35% improvement, motor learning ? upregulate dopamine

‌

24 – Ambroxol

www.parkinson.org/blog/science-news/ambroxol

25 – Vitamin B1