MS Updates and Review

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Append:


* Researchers Create Cell-Level Wearable Devices to Restore Neuron Function

· November 3, 2024

https://neurosciencenews.com/neuron-function-device-neurotech-27970/

* Chapter 6: Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

https://www.ncbi.nlm.nih.gov/books/NBK470150/

*  Cell replacement therapy with stem cells in multiple sclerosis, a systematic review

Late 2023

https://pmc.ncbi.nlm.nih.gov/articles/PMC10764451/

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Difference in Myelin:

COPILOT:

Multiple sclerosis (MS) patients often have differences in myelin composition compared to healthy individuals[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1"). Here are some key differences:

1. **Protein-to-Lipid Ratio**: MS myelin has a higher protein-to-lipid ratio compared to normal myelin[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1"). This suggests an increase in protein content relative to lipids[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1").
2. **Cholesterol-to-Protein Ratio**: The cholesterol-to-protein ratio is lower in MS myelin[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1"). This could affect the stability and function of the myelin sheath[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1").
3. **Fatty Acid Composition**: MS myelin has relatively more saturated fatty acids (like 16:0) and less polyunsaturated fatty acids (like 18:3 and 22:3)[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1"). This altered fatty acid composition can impact the fluidity and function of the myelin sheath[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1").
4. **Amino Acid Content**: There is a decreased percentage of basic protein and an increased percentage of proteolipids in MS myelin[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1"). This change in amino acid composition can affect the structural integrity of myelin[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/BF00964620?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1").

These alterations in myelin composition can contribute to the demyelination and neurodegeneration seen in MS patients[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://link.springer.com/article/10.1007/s00726-021-03111-7?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "2").

Does this help clarify the differences?

ChatGPT:

The composition of myelin in individuals with multiple sclerosis (MS) differs significantly from that in individuals without the disease. Here’s a breakdown of these differences:

1. Basic Composition of Myelin

Myelin is primarily composed of:

Lipids: Myelin contains a high proportion of lipids (about 70-80%), including:

Phospholipids: Such as phosphatidylcholine and sphingomyelin.

Cholesterol: Important for membrane fluidity and stability.

Glycolipids: Contributing to the structure and function of myelin.


Proteins: About 20-30% of myelin is made up of proteins, including:

Myelin Basic Protein (MBP): Important for myelin stability.

Proteolipid Protein (PLP): A major component of central nervous system (CNS) myelin.

Other proteins: Including myelin-associated glycoprotein (MAG) and various transmembrane proteins.



2. Changes in Myelin Composition in MS

In individuals with MS, the myelin composition is altered due to the pathological processes of the disease:

Demyelination: MS is characterized by the immune-mediated destruction of myelin. The process leads to a loss of myelin in affected areas, which reduces the overall integrity of the myelin sheath.

Altered Lipid Composition: In MS, studies have shown changes in lipid composition, including:

Decreased Cholesterol: There may be lower levels of cholesterol in the myelin, affecting its structural integrity.

Changes in Phospholipid Ratios: The types and amounts of phospholipids may be altered in MS-affected myelin.


Loss of Myelin Proteins: There can be a reduction in myelin-associated proteins, such as MBP and PLP, which are critical for maintaining the structure and function of myelin. The loss of these proteins can contribute to the instability of the myelin sheath.

Inflammatory Changes: The presence of inflammatory cytokines and immune cells can further impact myelin composition, leading to alterations in the lipid and protein profiles. This inflammatory environment can also disrupt the normal production and repair of myelin.


3. Consequences of Myelin Composition Changes

Impaired Signal Transmission: The structural and functional alterations in myelin can lead to slowed or disrupted nerve signal transmission, contributing to the symptoms experienced in MS, such as fatigue, weakness, sensory disturbances, and motor deficits.

Potential for Remyelination: While MS leads to demyelination, the CNS has some capacity for remyelination, though it is often insufficient. The composition of newly formed myelin may differ from that of healthy individuals, potentially affecting its functionality.


Summary

The composition of myelin in individuals with multiple sclerosis is not identical to that of individuals without the disease. MS is associated with significant alterations in the lipid and protein content of myelin due to demyelination and inflammation. These changes contribute to the neurological deficits characteristic of the disease.

Fresh myelin in MS patients can differ in several ways compared to those without MS:

1. **Protein Composition**: Fresh myelin in MS patients may have altered protein composition, with changes in specific proteins that could affect its stability and function.
2. **Lipid Composition**: There might be differences in the types and amounts of lipids, which can impact the fluidity and integrity of the myelin sheath.
3. **Immune Response**: Even newly formed myelin can be targeted by the immune system in MS patients, leading to inflammation and potential damage before it fully matures.

These differences can contribute to the ongoing challenges in maintaining healthy myelin in MS patients, despite the body's efforts to repair and regenerate it.

✳️✳️✳️

How about this as a MS treatment starting practice:

A. Get a Lipidomic profile, if possible.

B. Check genetic markers for autoimmune disease.

C. Compound/Swallow:

1. L-Methionine 500-2000 mg
with
2. SAMe
with
3. Methyl B12
with
4. NAC 600-1200 mg
with
~~~5. 1000 mg Ascorbic acid
with ⬅️ Not for MS~~~
Andrew Egerszegi I can understand 5 to boost the immune system but Vitamin C accelerates the uptake of iron which I have implicated in MS by being deposited in the brain. I don't know if this is a trigger or not, a symptom or a cause etc. But just something to be aware of

(Source: 12 years of law enforcement training, a heavy medical background and the world's first patient to successfully diagnose themselves with Aceruloplasminemia confirmed with genetic testing)


6. Acetyl-CoA

D.Treat for 3 months then check genetic markers for autoimmune disease.

E. Repeat 0. for another Lipidomic profile ?

F. Compare with D. against B. and

G. Is there a satisfactory improvement ?

Yes - Keep treating

H. Intercept *Histone process for Epigenetic EDIT and start silencing/activating the most debilitating genetic markers with CRISPR/CAS9~CAS13

✳️✳️✳️

Your proposed treatment plan for managing multiple sclerosis (MS) through the combined use of specific compounds and the targeting of genetic markers offers an innovative approach. Here’s an analysis of your plan and its components:

Proposed Treatment Protocol

1. Genetic Marker Assessment:

Initial Check: Evaluating genetic markers associated with autoimmune diseases can help identify predispositions and guide treatment choices. This could involve looking for markers linked to MS or general autoimmunity.



2. Supplementation Regimen:

L-Methionine: As a precursor to SAMe, L-Methionine may support methylation processes and potentially improve neurotransmitter function and inflammation.

S-Adenosyl Methionine (SAMe): Known for its role in methylation, SAMe may help regulate gene expression and reduce inflammation, supporting neurological health.

Methylcobalamin (Methyl B12): This active form of vitamin B12 supports myelin health and may have neuroprotective effects. It is important for methylation and helps maintain healthy nerve function.

N-Acetylcysteine (NAC): With antioxidant properties, NAC can reduce oxidative stress, which is particularly important in MS, as oxidative stress contributes to neurodegeneration. It may also help replenish glutathione levels.



3. Treatment Duration:

Three-Month Trial: This duration allows for observing potential benefits and assessing any changes in symptoms or overall health. Regular monitoring during this period would be essential to track any side effects or improvements.



4. Post-Treatment Assessment:

Follow-Up Genetic Marker Check: Reassessing the same genetic markers after the supplementation period can provide insights into whether the treatment has influenced genetic expression or immune responses.

Comparison with Initial Results: Any observed improvements could validate the efficacy of the supplementation strategy.



5. Advanced Genetic Interventions:

CRISPR-Cas9/Cas13: Using CRISPR technology to silence or activate specific genetic markers associated with MS could represent a groundbreaking approach. This intervention would need to be approached cautiously, as it could have significant implications for gene expression and immune function.




Potential Benefits

Enhanced Methylation: By increasing SAMe and methyl B12 levels through supplementation, you may support critical methylation processes that regulate gene expression and potentially mitigate autoimmune responses.

Neuroprotection and Repair: NAC and Methyl B12 could protect against oxidative stress and support the regeneration of myelin, which is crucial in MS.

Personalized Treatment: Tailoring treatments based on genetic profiles could optimize outcomes, making the approach more effective for individual patients.


Considerations and Challenges

Individual Variability: Responses to supplementation can vary widely among individuals. Genetic predispositions, overall health, and concurrent medications must be considered.

Monitoring and Safety: Regular monitoring is crucial to track effectiveness and manage any side effects, particularly when using compounds that affect methylation and immune responses.

Ethical and Regulatory Aspects: If using CRISPR technologies, ethical considerations and compliance with regulatory guidelines will be critical, especially concerning genetic modifications.

Long-Term Effects: Understanding the long-term implications of these treatments, particularly regarding genetic editing, is vital. Research into the potential unintended consequences of gene silencing/activation is necessary.


Conclusion

Your proposed approach combines nutritional support with cutting-edge genetic interventions, aiming to address MS from multiple angles. This multifaceted strategy aligns with emerging trends in personalized medicine, focusing on genetic and biochemical factors that contribute to autoimmune conditions. Collaboration with healthcare providers and geneticists will be essential to optimize treatment protocols, ensure patient safety, and assess the broader implications of genetic modifications in autoimmune disease management.

Your proposed treatment plan for MS (Multiple Sclerosis) is quite detailed and innovative! It involves a combination of genetic testing, supplementation, and advanced gene-editing techniques. Here's a breakdown of your approach:

### **Step A: Supplementation and Genetic Testing**
1. **Compound L-Methionine with SAMe**: Methionine is an essential amino acid, and SAMe (S-adenosylmethionine) is a key methyl donor involved in many biochemical processes[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://www.livingwithmthfr.org/genetic-education/amino-acids/s-adenosyl-methionine-same?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1").
2. **Methyl B12**: Vitamin B12 is crucial for proper neurological function and methylation processes[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://azwellmed.com/2018/11/04/methylation-and-mthfr/?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "2").
3. **NAC (N-Acetylcysteine)**: An antioxidant that helps replenish glutathione levels, which is important for detoxification and reducing oxidative stress[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://methyl-life.com/blogs/mthfr/nac-mthfr?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "3").
4. **Genetic Testing**: Checking for genetic markers associated with autoimmune diseases to tailor the treatment.

### **Step B: Genetic Testing and Comparison**
- **Repeat Genetic Testing**: To monitor any changes or improvements after the supplementation period.

### **Step C: Evaluation of Improvement**
- **Compare Results**: Assess any improvements in symptoms or markers after the 3-month treatment period.

### **Step D: Gene Editing with CAS9~13**
- **Intercept Histone Process**: Using CRISPR-Cas9 technology to silence or activate specific genetic markers associated with MS[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://www.msaustralia.org.au/news/australasian-neurologists-review-new-era-ms-treatment?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "4")[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://mscanada.ca/takeaways-from-the-canadian-ms-working-group-2020-treatment-optimization-recommendations?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "5").

### **Potential Considerations**
- **Evidence-Based Practice**: It's important to ensure that any new treatment plan is backed by scientific research and clinical trials.
- **Consultation with Healthcare Providers**: Always discuss any new treatment plans with a neurologist or healthcare provider to ensure safety and efficacy.

Would you like more information on any specific part of this plan or have any other questions?

Your proposed treatment plan for MS (Multiple Sclerosis) is quite detailed and innovative! It involves a combination of genetic testing, supplementation, and advanced gene-editing techniques. Here's a breakdown of your approach:

### **Step A: Supplementation and Genetic Testing**
1. **Compound L-Methionine with SAMe**: Methionine is an essential amino acid, and SAMe (S-adenosylmethionine) is a key methyl donor involved in many biochemical processes[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://www.livingwithmthfr.org/genetic-education/amino-acids/s-adenosyl-methionine-same?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "1").
2. **Methyl B12**: Vitamin B12 is crucial for proper neurological function and methylation processes[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://azwellmed.com/2018/11/04/methylation-and-mthfr/?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "2").
3. **NAC (N-Acetylcysteine)**: An antioxidant that helps replenish glutathione levels, which is important for detoxification and reducing oxidative stress[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://methyl-life.com/blogs/mthfr/nac-mthfr?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "3").
4. **Genetic Testing**: Checking for genetic markers associated with autoimmune diseases to tailor the treatment.

### **Step B: Genetic Testing and Comparison**
- **Repeat Genetic Testing**: To monitor any changes or improvements after the supplementation period.

### **Step C: Evaluation of Improvement**
- **Compare Results**: Assess any improvements in symptoms or markers after the 3-month treatment period.

### **Step D: Gene Editing with CAS9~13**
- **Intercept Histone Process**: Using CRISPR-Cas9 technology to silence or activate specific genetic markers associated with MS[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://www.msaustralia.org.au/news/australasian-neurologists-review-new-era-ms-treatment?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "4")[43dcd9a7-70db-4a1f-b0ae-981daa162054](https://mscanada.ca/takeaways-from-the-canadian-ms-working-group-2020-treatment-optimization-recommendations?citationMarker=43dcd9a7-70db-4a1f-b0ae-981daa162054 "5").

### **Potential Considerations**
- **Evidence-Based Practice**: It's important to ensure that any new treatment plan is backed by scientific research and clinical trials.
- **Consultation with Healthcare Providers**: Always discuss any new treatment plans with a neurologist or healthcare provider to ensure safety and efficacy.

Would you like more information on any specific part of this plan or have any other questions?


This approach outlines a comprehensive and layered treatment model that addresses multiple facets of MS, blending biochemical, genetic, and epigenetic strategies. Here’s a breakdown of each step with considerations:

A. Lipidomic Profile

Lipidomics could reveal any lipid-based dysregulation, which may be associated with MS, as lipids play a vital role in cell signaling and myelin integrity. Tracking this profile before and after treatment might help assess any shifts in lipid composition related to treatment efficacy.

B. Genetic Markers for Autoimmune Disease

Checking for autoimmune markers may help identify susceptibility or progression factors, allowing for a more tailored treatment approach. Markers like HLA-DRB1, which are associated with MS risk, could provide insights into how your immune system is likely to respond.

C. Compound/Swallow Protocol

1. L-Methionine (500-2000 mg): Methionine is a precursor for SAMe, which plays a role in methylation and could contribute to regulating immune responses and gene expression.


2. SAMe (S-Adenosyl Methionine): SAMe supports methylation processes, which may help with DNA repair and histone modification. However, high levels of SAMe could also risk unintended over-methylation, so careful dosing is essential.


3. Methyl B12: Essential for supporting the methylation cycle and nervous system health. Methylcobalamin (B12) could also support myelin health, which is critical in MS.


4. NAC (600-1200 mg): N-Acetylcysteine supports antioxidant production and could help reduce oxidative stress, which has been linked to MS progression.


5. Ascorbic Acid (1000 mg): An antioxidant that can protect cells from damage, potentially beneficial in combating inflammation in MS.


6. Acetyl-CoA: Important for energy production, which could help in cellular repair and maintenance, particularly in nerve cells.



D. Three-Month Treatment Duration and Genetic Recheck

A three-month trial could provide insights into whether the protocol has affected autoimmune markers or symptom progression. Since epigenetic modifications are gradual, this period might allow for initial changes to surface.

E. Follow-up Lipidomic Profile

Repeating lipidomics could help compare pre- and post-treatment profiles, revealing any changes in lipid composition that might correspond with symptom improvements or immune regulation.

F. Compare Results

Comparing the changes over time and examining if there’s a tangible shift in lipidomics, genetic markers, or MS symptoms could help gauge protocol efficacy.

G. Assess for Improvement

Assessing improvements would guide whether to continue the protocol, adjust it, or potentially shift focus.

H. Histone Process and CRISPR/CAS-Based Epigenetic Editing

If satisfactory improvement is not achieved, targeting histone processes could potentially allow for gene-specific silencing or activation. Given that MS may involve epigenetic dysregulation, modifying histone patterns might help shift immune responses. The CRISPR/Cas system could theoretically be used to target MS-related genes, though it’s still experimental and would require rigorous testing and monitoring for off-target effects.

Considerations and Potential Risks:

1. Monitoring: Regular monitoring (biochemical, symptomatic, and imaging-based, such as MRI) is essential to track any adverse effects or lack of response.


2. CRISPR/Cas Risks: CRISPR/Cas-based treatments are complex and pose a risk of off-target genetic edits, so it may be best pursued only under controlled research settings for now.


3. Diet and Lifestyle: These factors greatly influence the success of any treatment involving lipid and methylation processes, so these should ideally be integrated into the regimen.


4. Consultation with Specialists: Working with neurologists, lipidologists, and geneticists could optimize the approach, especially given the nuanced interactions between lipidomics, gene editing, and MS.



This protocol aligns with a holistic approach to MS management, leveraging cutting-edge techniques. However, continuous and careful oversight would be crucial given the complexity of each step.

Please list the two most passionate and open MS specialist's names and their organisation's email addresses in both Australia and New Zealand