It is not good enough to simply target stabilisation or slowing down of disability worsening. I want to participate in a trial that offers an improvement in functioning.
To prevent is always ‘easier’ and better than to cure. We should however leave no one behind. One of the biggest issues is that when medical MS interventions work in active inflammatory relapsing MS, they don’t work in progressive MS. The other way around is that successful progressive MS therapies do work in relapsing MS.
So why does the medical research establishment still focus on creating similar Disease Modifying Therapies addressing the immune system. Do we actually need more of the same therapies with a similar mode of action and effectiveness, but with different side effect profile or ‘novel’ route of administration? A paradigm shift in medical research is urgently needed to actually develop cures for all different types of People with MS.
Preventing cumulative neurological disability to eventually reach the level of Advanced Multiple Sclerosis should nowadays already be a tangible reality with several high efficacy Disease Modifying Therapies (IRT’s, alemtuzumab, etc) addressing the adaptive immune system attacking myelin in the Central Nervous System ultimately leading to neurodegeneration.
New treatments for Progressive MS addressing for instance the innate immune system (BTK, Mastinib, etc) and remyelination strategies (CNM-Au8, dendritic cells, NVG-291 etc) are also approaching the market in the next 5 to 10 years after decades of research if proved effective. The hope is this will halt progressing neurodegeneration atrophying the Central Nervous System.
To prevent MS (perhaps via a EBV vaccine) and halting its progressive course should be a more achievable goal in the next 5 to 10 years opposed to actually curing or at least improving cumulative neurological disability leading to advanced levels of MS. If we can prevent this devastating disease it will naturally disappear in time.
However currently the biggest unmet need lies with those people who experience daily struggles with varied advanced levels of disability and can even expect progressive worsening over time.
Remyelination strategies will only be effective if it is applied early in the disease course when there is active inflammation and for instance neurological reserve via neuroplasticity to compensate lost neurological function. Remyelination will not cure advanced progressive disease. It might slow down progression.
Other novel to be developed strategies are needed to improve or even reverse lost neurological function ultimately curing Advanced (progressive) MS.
In an acute MS lesion, the window of opportunity for both neuroprotection and remyelination may be relatively short. In other words, if you don’t protect and remyelinate damaged axons quickly, they may degenerate and hence remyelination therapies may fail. Also, some degree of neuroinflammation particularly of the regulatory type is beneficial for regenerative responses.
This so-called ‘window of opportunity’ has been referred to as the inflammatory penumbra and may limit the potential of remyelination therapies to a biological window of potentially weeks or possibly months. After acute optic neuritis retinal nerve fibre thinning or optic nerve atrophy may take somewhere between four to six months, respectively. It is therefore hard to imagine a treatment working beyond this window.
Improving or even reversing longstanding accumulated neurological disability is the biggest unmet need in the underserved Advanced (progressive) MS community.
It should, therefore, be abundantly clear to the Advanced (progressive) MS community that remyelination therapies alone will have no to limited effect due to the inflammatory penumbra. Only new acute inflammatory lesions are suitable for remyelination and neuroprotection.
Again, like with current DMT’s mainly (Early) Relapsing MS and early inflammatory progressive MS is addressed with remyelination and neuroprotection Research, and research to create adequate treatments for non-inflammatory and/or smouldering Progressive MS are still lacking.
I therefor do wonder why for instance the progressive MS Alliance and other national ms societies and foundations so strongly focus on myelin repair therapies for Progressive MS.
Cumulative neurological disability via axonal degeneration and CNS atrophy due to neurodegeneration and/or inflammation will not be adequately addressed with remyelination therapies alone. In best case scenario it will limited and/or prevent progression in (Advanced) Progressive MS.
At present PwMS, especially people with progressive MS, have unrealistically high expectations for potential remyelination therapies while those living with advanced levels of disability are likely to not benefit from them.
Therefore, we must manage the expectations to the underserved progressive MS patient community and explain the complexities and challenges posed by remyelination and neurorestorative therapies.
The way I see it, in 5 to 10 years’ time there will be roughly 2 types of MS patients.
1. Early MS diagnosis with a hit hard induction therapy or perhaps a virus (EBV?) vaccine in combination with possible remyelination medicines resulting in low EDSS and stable MS. (Remission / cure?)
2. MS Patients with cumulative acquired disability with hopefully CNS penetrable medical interventions (BTK? EBV vaccine? Temelimab? Etc) to address smouldering inflammation stopping progression and keeping them stable.
For those PwMS in the second group other novel medical interventions need to be developed next to remyelination alone to improve or even reverse longstanding accumulated neurological disability and improve quality of life. That’s the biggest unmet need for these patients who are effected the most by this gruesome and unforgiving disease.
I would like to take part in trials, but I (perhaps wrongly) thought my neurologist had to put me forward for them. Should I be looking for trials myself?
I had my first course of Lemtrada almost 6 months ago, so I hope one doesn't need to have it within the first 2-5 years of having MS; I've had MS a *lot* longer than that.
I totally agree with giving pwms the option of Lemtrada/HSCT as soon as they're diagnosed. I would have chosen that. It was very hard to get Lemtrada and I've never had the option of HSCT. I do want to stop deterioration, but most of all I want something to make me feel better. That's all I ever wanted.
As a 61 year old Secondary progressive M.S sufferer I am absolutely thrilled at the amazing news that M.S treatments are progressing so much I have two daughters whom I constantly worry will inherit this awful disease so as you can imagine any progress in treatments to start sooner is very well received. Now to risk offending others( not meaning to I promise and probably a bit selfish) while as I say quite honestly I am thrilled with all progress can I ask what's being done for those of us with established disabilities. From what I keep reading on your blogs and many others if I had been given treatments on diagnosis 15 years ago my disabilities may not have been so bad .My question therefore is. Is there anything that can be done to help those of us in this situation we seem to be the forgotten tribe and I can assure you I have put my name forward with my Neurologist and M,S nurse for any trials to have not been given the opportunity to try any.Therefore may I please inform you if you are looking for volunteers for ANY!! Trials look no further
What about the default approach for remyelination, mesenchymal stem cell treatment, that’s been tossed around for nearly 20 years? Is the general approach misguided or have we simply been doing it wrongly?
So why not tweak dosage/frequency of promising agents further before attempting to move the goal posts of study endpoints?
And if funding only allowed one shot at phase III, where are the national MS societies? Fairly sad that so many decades after promises were made to “tackle every possible avenue” each and every new treatment idea still requires a robust business case in order to go anywhere..
I'm a 57 yr old male diagnosed Oct 21 with 5 brain lesions and 1 cervical C7. My first noticeable symptoms were mild tingling in small and ring finger and Lehrmitts 11 months ago. I've gone from no noticeable muscle weakness 6 months ago to moderate leg weakness, mild arm weakness and fine motor tremor in my hands some of the time. I was offered ofatumumab which I began in Dec but have steadily declined since with 2 new lesions appearing on my follow up MRI in February, 1 right parietal and 1 C6. I have ongoing attacks which typically cause existing symptoms to flare but no new symptoms and I seem to get some resolution but not complete recovery, hence the decline.
After reading your prior posts regarding alemtuzumab and AHSCT I discussed the possibility with my neurologist, only to be told they are too risky with alemtuzumab having a 40% secondary autoimmune risk. After reviewing the long term study data for alemtuzumab it appears the major risk of secondary autoimmune is thyroid related which is, to my understanding, a very manageable disease.
There are other risk factors of course but they are all around 1% or less.
So yes, I agree that these higher efficacy treatments should be made more available and PWMS given all the information and allowed to decide their own treatment path. I'd take a thyroid autoimmune problem over losing my legs and arms, it's a no brainer.
And I also agree that HCP's should be advising PWMS to actively engage in neurorehabilitation through intermittent fasting and exercise to give the body the optimum chance to heal. For some reason my neurologist has shot down my suggestion that diet is crucial, due to a lack of solid scientific evidence, however there appears to be a significant amount of literature and anecdotal evidence linking saturated fats, red meat and possibly dairy to a poorer ms outcome. Cutting these things out of your diet or at least restricting their intake coupled with fasting and exercise should be first line defence. Readily available and cost effective.
Prof G, in your opinion are my demographics, 57yr old male, suitable for alemtuzumab or is the age related possible neurodegeneration a determining factor against it?
There doesn't seem to be much information available relating to my age group.
I also would like to see more trials focused on reversal and cure. If the scientific industry can develop and manufacture a vaccine in approximately 2 years that neutralizes covid, why can’t the scientific industry find a treatment to reverse MS in all the decades of research?
Role of bovine adiponectin contaminated vaccine induced autoimmunity in the etiology of type 2 diabetes, atherosclerosis related coronary artery disease, cerebral infarction, obesity and polycystic ovarian syndrome; epicutaneous immunotherapy home remedy as a potential prevention or treatment approach
MS patients need to be more proactive. Clemastine and memantine are both incredibly easy to obtain without a prescription and have known safety profiles. Why does your patient feel she needs to be in this Cambridge trial (where she anyway has a 50% chance of getting placebo)? If she feels so strongly about it she should take matters into her own hands. The stakes for MS patients are extremely high.
By the way, I agree fully with your take on remyelinating therapies. Trying to clear more underlying pathology so natural repair can take place is the way to go.
HSCT just terrifies - the immune ablation and weeks in the hospital to recover. I got on a med/hi efficacy DMT ASAP after CIS dx (retroactively updated to RRMS) and didn't LOVE accepting the PML & malignancy risk, but was okay with the balance of risk from SAEs vs risk from MS. Maybe it's because I am stable without it, or because my professional life exposes me to stories about stem cell transplant, but it freaks me out. It also sort of bothers me that like, my immune system is busted, so why would replacing my cells with my own cells help? I mean, obviously it DOES, but it seems like you'd just develop MS again? I guess I'm showing that I haven't done my research. But also I guess if it took 30 years to develop the first time, and 30 the second time, that's a calculus some people would be cool with. Another concern is that it HSCT might render you ineligible (cumulative risk from conditioning agents) for future therapies like reengineered T cells: https://abatatx.com/our-approach/
I also agree about poorly designed trials - it's so expensive to do science that this happens at every level and compounds.
Wow, that’s a lot of questions and a whole can of worms! Unfortunately in the UK HSCT is still so difficult to access and I think part of this problem is to do with budgets and NHS resources (I don’t know if it still comes out of the haematologists budget). In the ideal world these treatments would be done early before there is so much damage to the myelin. There aren’t many of us that can access the funds to have this treatment abroad before deteriorating too far. I mentioned in my last response how my relapses would leave me in a wheelchair for months at a time, with extreme fatigue, dizziness and difficulty using my right arm. EDSS is a rubbish indicator of disability because I was still given a score of 3 before treatment. Now my EDSS is probably about 1 or 2 (I don’t really focus on my score, all I know is I don’t relapse, do over an hour in the gym and play golf again). I worked hard on my rehabilitation after and my improvements are either due to neuro-plasticity or MRI scans aren’t showing the improvements to the myelin. If you saw my MRI scans with all the lesions on my cervical spine you probably would expect me to be in a wheelchair permanently, I haven’t been made aware of any changes.
I’m not sure about intermittent fasting, for someone with a BMI of 19 like myself I have to eat regularly. I do however have 14 hour gap between my evening meal and breakfast (due to reflux).
People like myself probably won’t want to take part in clinical trials, unless they’re re-purposing drugs that they know the full side effects. There are others that I know who have had HSCT who still have significant disability that would be part of demyelination trials.
Excluding those who haven’t been able to have the MS stabilised would be devastated to be excluded from myelin trials. It’s all that offers hope for some people. If a successful treatment was found they would no doubt not qualify for it if they were excluded from the trial.
I forgot the best Hormetic exercise of all: fasting. I never understand why all PWMS don't do at least a 16 hour IF. How about a mono-variable study on MS and fasting. And why don't PWMS know about BDNF? It seems so key to promoting healing. Dr. G, you noted in your previous note the importance of agency and a healthy lifestyle. Why dint PWMS run their own studies on themselves by overhauling their lifestyles, incorporate daily hermetic exercises, and see what happens??!!
Great article! As you note, use it or lose it. Hormesis exercises are so key IMHO. But PWMS think I am crazy when I mention it. What if we had a multi-variable lifestyle medicine overhaul trial that has for goal promoting neurological environmental healing. Factors include: anti-oxidant, nutrient dense diet, daily physical exercise of cardio and weights, daily mental learning (if really challenging yourself! Like learning a foreign language or instrument), stress management and access to weekly coaching. Just think of the potential outcomes!
To prevent is always ‘easier’ and better than to cure. We should however leave no one behind. One of the biggest issues is that when medical MS interventions work in active inflammatory relapsing MS, they don’t work in progressive MS. The other way around is that successful progressive MS therapies do work in relapsing MS.
So why does the medical research establishment still focus on creating similar Disease Modifying Therapies addressing the immune system. Do we actually need more of the same therapies with a similar mode of action and effectiveness, but with different side effect profile or ‘novel’ route of administration? A paradigm shift in medical research is urgently needed to actually develop cures for all different types of People with MS.
Preventing cumulative neurological disability to eventually reach the level of Advanced Multiple Sclerosis should nowadays already be a tangible reality with several high efficacy Disease Modifying Therapies (IRT’s, alemtuzumab, etc) addressing the adaptive immune system attacking myelin in the Central Nervous System ultimately leading to neurodegeneration.
New treatments for Progressive MS addressing for instance the innate immune system (BTK, Mastinib, etc) and remyelination strategies (CNM-Au8, dendritic cells, NVG-291 etc) are also approaching the market in the next 5 to 10 years after decades of research if proved effective. The hope is this will halt progressing neurodegeneration atrophying the Central Nervous System.
To prevent MS (perhaps via a EBV vaccine) and halting its progressive course should be a more achievable goal in the next 5 to 10 years opposed to actually curing or at least improving cumulative neurological disability leading to advanced levels of MS. If we can prevent this devastating disease it will naturally disappear in time.
However currently the biggest unmet need lies with those people who experience daily struggles with varied advanced levels of disability and can even expect progressive worsening over time.
Remyelination strategies will only be effective if it is applied early in the disease course when there is active inflammation and for instance neurological reserve via neuroplasticity to compensate lost neurological function. Remyelination will not cure advanced progressive disease. It might slow down progression.
Other novel to be developed strategies are needed to improve or even reverse lost neurological function ultimately curing Advanced (progressive) MS.
In an acute MS lesion, the window of opportunity for both neuroprotection and remyelination may be relatively short. In other words, if you don’t protect and remyelinate damaged axons quickly, they may degenerate and hence remyelination therapies may fail. Also, some degree of neuroinflammation particularly of the regulatory type is beneficial for regenerative responses.
This so-called ‘window of opportunity’ has been referred to as the inflammatory penumbra and may limit the potential of remyelination therapies to a biological window of potentially weeks or possibly months. After acute optic neuritis retinal nerve fibre thinning or optic nerve atrophy may take somewhere between four to six months, respectively. It is therefore hard to imagine a treatment working beyond this window.
Improving or even reversing longstanding accumulated neurological disability is the biggest unmet need in the underserved Advanced (progressive) MS community.
It should, therefore, be abundantly clear to the Advanced (progressive) MS community that remyelination therapies alone will have no to limited effect due to the inflammatory penumbra. Only new acute inflammatory lesions are suitable for remyelination and neuroprotection.
Again, like with current DMT’s mainly (Early) Relapsing MS and early inflammatory progressive MS is addressed with remyelination and neuroprotection Research, and research to create adequate treatments for non-inflammatory and/or smouldering Progressive MS are still lacking.
I therefor do wonder why for instance the progressive MS Alliance and other national ms societies and foundations so strongly focus on myelin repair therapies for Progressive MS.
Cumulative neurological disability via axonal degeneration and CNS atrophy due to neurodegeneration and/or inflammation will not be adequately addressed with remyelination therapies alone. In best case scenario it will limited and/or prevent progression in (Advanced) Progressive MS.
At present PwMS, especially people with progressive MS, have unrealistically high expectations for potential remyelination therapies while those living with advanced levels of disability are likely to not benefit from them.
Therefore, we must manage the expectations to the underserved progressive MS patient community and explain the complexities and challenges posed by remyelination and neurorestorative therapies.
The way I see it, in 5 to 10 years’ time there will be roughly 2 types of MS patients.
1. Early MS diagnosis with a hit hard induction therapy or perhaps a virus (EBV?) vaccine in combination with possible remyelination medicines resulting in low EDSS and stable MS. (Remission / cure?)
2. MS Patients with cumulative acquired disability with hopefully CNS penetrable medical interventions (BTK? EBV vaccine? Temelimab? Etc) to address smouldering inflammation stopping progression and keeping them stable.
For those PwMS in the second group other novel medical interventions need to be developed next to remyelination alone to improve or even reverse longstanding accumulated neurological disability and improve quality of life. That’s the biggest unmet need for these patients who are effected the most by this gruesome and unforgiving disease.
I would like to take part in trials, but I (perhaps wrongly) thought my neurologist had to put me forward for them. Should I be looking for trials myself?
I had my first course of Lemtrada almost 6 months ago, so I hope one doesn't need to have it within the first 2-5 years of having MS; I've had MS a *lot* longer than that.
I totally agree with giving pwms the option of Lemtrada/HSCT as soon as they're diagnosed. I would have chosen that. It was very hard to get Lemtrada and I've never had the option of HSCT. I do want to stop deterioration, but most of all I want something to make me feel better. That's all I ever wanted.
As a 61 year old Secondary progressive M.S sufferer I am absolutely thrilled at the amazing news that M.S treatments are progressing so much I have two daughters whom I constantly worry will inherit this awful disease so as you can imagine any progress in treatments to start sooner is very well received. Now to risk offending others( not meaning to I promise and probably a bit selfish) while as I say quite honestly I am thrilled with all progress can I ask what's being done for those of us with established disabilities. From what I keep reading on your blogs and many others if I had been given treatments on diagnosis 15 years ago my disabilities may not have been so bad .My question therefore is. Is there anything that can be done to help those of us in this situation we seem to be the forgotten tribe and I can assure you I have put my name forward with my Neurologist and M,S nurse for any trials to have not been given the opportunity to try any.Therefore may I please inform you if you are looking for volunteers for ANY!! Trials look no further
What about the default approach for remyelination, mesenchymal stem cell treatment, that’s been tossed around for nearly 20 years? Is the general approach misguided or have we simply been doing it wrongly?
OPCs administered intrathecally and repeatedly (>6x) over several months apparently yield demonstrable results! https://www.tischms.org/phase-ii-preliminary-analysis-results
So why not tweak dosage/frequency of promising agents further before attempting to move the goal posts of study endpoints?
And if funding only allowed one shot at phase III, where are the national MS societies? Fairly sad that so many decades after promises were made to “tackle every possible avenue” each and every new treatment idea still requires a robust business case in order to go anywhere..
Is it only HSCT and alemtuzumab that have this potential or other high-efficacy treatments i.e. Cladribine/Ocrelizumab if started early enough?
Also is it possible to determine how late is too late to see the same effects i.e. EDSS score on initiation?
I'm a 57 yr old male diagnosed Oct 21 with 5 brain lesions and 1 cervical C7. My first noticeable symptoms were mild tingling in small and ring finger and Lehrmitts 11 months ago. I've gone from no noticeable muscle weakness 6 months ago to moderate leg weakness, mild arm weakness and fine motor tremor in my hands some of the time. I was offered ofatumumab which I began in Dec but have steadily declined since with 2 new lesions appearing on my follow up MRI in February, 1 right parietal and 1 C6. I have ongoing attacks which typically cause existing symptoms to flare but no new symptoms and I seem to get some resolution but not complete recovery, hence the decline.
After reading your prior posts regarding alemtuzumab and AHSCT I discussed the possibility with my neurologist, only to be told they are too risky with alemtuzumab having a 40% secondary autoimmune risk. After reviewing the long term study data for alemtuzumab it appears the major risk of secondary autoimmune is thyroid related which is, to my understanding, a very manageable disease.
There are other risk factors of course but they are all around 1% or less.
So yes, I agree that these higher efficacy treatments should be made more available and PWMS given all the information and allowed to decide their own treatment path. I'd take a thyroid autoimmune problem over losing my legs and arms, it's a no brainer.
And I also agree that HCP's should be advising PWMS to actively engage in neurorehabilitation through intermittent fasting and exercise to give the body the optimum chance to heal. For some reason my neurologist has shot down my suggestion that diet is crucial, due to a lack of solid scientific evidence, however there appears to be a significant amount of literature and anecdotal evidence linking saturated fats, red meat and possibly dairy to a poorer ms outcome. Cutting these things out of your diet or at least restricting their intake coupled with fasting and exercise should be first line defence. Readily available and cost effective.
Prof G, in your opinion are my demographics, 57yr old male, suitable for alemtuzumab or is the age related possible neurodegeneration a determining factor against it?
There doesn't seem to be much information available relating to my age group.
I also would like to see more trials focused on reversal and cure. If the scientific industry can develop and manufacture a vaccine in approximately 2 years that neutralizes covid, why can’t the scientific industry find a treatment to reverse MS in all the decades of research?
I don't think you will hear any counter arguments here as everyone is 100% with you!
May apply to all autoimmune diseases.
Role of bovine adiponectin contaminated vaccine induced autoimmunity in the etiology of type 2 diabetes, atherosclerosis related coronary artery disease, cerebral infarction, obesity and polycystic ovarian syndrome; epicutaneous immunotherapy home remedy as a potential prevention or treatment approach
https://doi.org/10.5281/zenodo.3261865
I hope participants fully understand the consequences of having plasma cells depleted... Personally I find cost is too much unless this is a cure.
What’s your view on this report, in today’s New Scientist? ‘MS reversed by transplanted immune cells that fight Epstein-Barr virus’ Thank you
MS patients need to be more proactive. Clemastine and memantine are both incredibly easy to obtain without a prescription and have known safety profiles. Why does your patient feel she needs to be in this Cambridge trial (where she anyway has a 50% chance of getting placebo)? If she feels so strongly about it she should take matters into her own hands. The stakes for MS patients are extremely high.
By the way, I agree fully with your take on remyelinating therapies. Trying to clear more underlying pathology so natural repair can take place is the way to go.
HSCT just terrifies - the immune ablation and weeks in the hospital to recover. I got on a med/hi efficacy DMT ASAP after CIS dx (retroactively updated to RRMS) and didn't LOVE accepting the PML & malignancy risk, but was okay with the balance of risk from SAEs vs risk from MS. Maybe it's because I am stable without it, or because my professional life exposes me to stories about stem cell transplant, but it freaks me out. It also sort of bothers me that like, my immune system is busted, so why would replacing my cells with my own cells help? I mean, obviously it DOES, but it seems like you'd just develop MS again? I guess I'm showing that I haven't done my research. But also I guess if it took 30 years to develop the first time, and 30 the second time, that's a calculus some people would be cool with. Another concern is that it HSCT might render you ineligible (cumulative risk from conditioning agents) for future therapies like reengineered T cells: https://abatatx.com/our-approach/
I also agree about poorly designed trials - it's so expensive to do science that this happens at every level and compounds.
Wow, that’s a lot of questions and a whole can of worms! Unfortunately in the UK HSCT is still so difficult to access and I think part of this problem is to do with budgets and NHS resources (I don’t know if it still comes out of the haematologists budget). In the ideal world these treatments would be done early before there is so much damage to the myelin. There aren’t many of us that can access the funds to have this treatment abroad before deteriorating too far. I mentioned in my last response how my relapses would leave me in a wheelchair for months at a time, with extreme fatigue, dizziness and difficulty using my right arm. EDSS is a rubbish indicator of disability because I was still given a score of 3 before treatment. Now my EDSS is probably about 1 or 2 (I don’t really focus on my score, all I know is I don’t relapse, do over an hour in the gym and play golf again). I worked hard on my rehabilitation after and my improvements are either due to neuro-plasticity or MRI scans aren’t showing the improvements to the myelin. If you saw my MRI scans with all the lesions on my cervical spine you probably would expect me to be in a wheelchair permanently, I haven’t been made aware of any changes.
I’m not sure about intermittent fasting, for someone with a BMI of 19 like myself I have to eat regularly. I do however have 14 hour gap between my evening meal and breakfast (due to reflux).
People like myself probably won’t want to take part in clinical trials, unless they’re re-purposing drugs that they know the full side effects. There are others that I know who have had HSCT who still have significant disability that would be part of demyelination trials.
Excluding those who haven’t been able to have the MS stabilised would be devastated to be excluded from myelin trials. It’s all that offers hope for some people. If a successful treatment was found they would no doubt not qualify for it if they were excluded from the trial.
I forgot the best Hormetic exercise of all: fasting. I never understand why all PWMS don't do at least a 16 hour IF. How about a mono-variable study on MS and fasting. And why don't PWMS know about BDNF? It seems so key to promoting healing. Dr. G, you noted in your previous note the importance of agency and a healthy lifestyle. Why dint PWMS run their own studies on themselves by overhauling their lifestyles, incorporate daily hermetic exercises, and see what happens??!!
Great article! As you note, use it or lose it. Hormesis exercises are so key IMHO. But PWMS think I am crazy when I mention it. What if we had a multi-variable lifestyle medicine overhaul trial that has for goal promoting neurological environmental healing. Factors include: anti-oxidant, nutrient dense diet, daily physical exercise of cardio and weights, daily mental learning (if really challenging yourself! Like learning a foreign language or instrument), stress management and access to weekly coaching. Just think of the potential outcomes!