multiple sclerosis

Review of literature:  stem cell therapy in multiple sclerosis

Virginia Thornley, M.D., Neurologist, Epileptologist
October 8, 2018
 
Introduction
Stem cell therapy is explored for certain types of cancer such as bone marrow cancer. Its therapeutic options have been experimentally being expanded to other disease such as multiple sclerosis. This seeks to review some of the literature on current research for stem cell therapy in multiple sclerosis. As yet, there are still ongoing research and experiments and is not yet  approved by the FDA as treatment for multiple sclerosis. This seeks to review mechanisms, small studies and experimental studies in multiple sclerosis.
Some mechanisms through which stem cell therapy may help
Natural killer cells are thought to attenuate Th17 cells which are pro-inflammatory after autologous hematopoietic stem cell treatment. It may not have effect on the Th1 cell but it seems to reduce the number of Th17 cells (1).
Comparing Wharton Jelly mesenchymal cell with bone marrow mesenchymal stem cell
One study shows that Wharton Jelly mesenchymal stem cell may be comparable to the gold standard bone marrow stem cell and may be more easily extracted. There is a different gene phenotype and are found to overexpress genes that impact neurotrophic support making it a great candidate for stem cell source in neurodegenerative diseases such as amyotrophic lateral sclerosis or Parkinson’s disease. It was found to cause greater neuronal maturation in neuroblastoma cells compared to bone marrow mesenchymal cells. Genes that influenced adhesion, proliferation and the immune system were found to be greater expressed in Wharton jelly mesenchymal stem cell (2).
 
aHSCT in fatigue
In one small study in 23 patients the use of autologous human stem cell treatment helped with symptoms of fatigue using the FIS or the fatigue impact scale (1). The median score in FIS was reduced by 36% with 4 patients with a complete reduction. Some even had gainful employment and returned to driving, measured with the EDSS or expanded disability status scale(3).
EED3C98A-1357-4407-AC7E-3D568DBA7D8F
 
A pilot study shows mesenchymal stem cell injection slows progression
In a pilot study of 4 patients, 3 had secondary progressive type while 1 was in the relapsing-remitting stage. Autologous bone marrow stem cells were injected and patients were followed for 2 years. Those with secondary progressive type stabilized with no further deterioration while the patient with relapsing remitting type had an attack. None of the MRI tests showed any new plaques or abnormalities(4).
Mesenchymal stem cell treatment is thought to be helpful as a neuroprogenitor and slows the neurodegeneration where standard medications may be ineffective (5).
Hematopoietic cell transplant  for relapsing-remitting multiple sclerosis
In one study of 25 patients looking at high dose immunotherapy and autologous hematopoietic stem cell therapy, peripheral blood stem cell grafts were CD34+ chosen. Immunosuppression was given beforehand. It was found to reduce relapses over a course of 3 years in patients with relapsing-remitting multiple sclerosis without serious adverse effects(6).
In summary
There is growing interest in stem cell therapy as a novel treatment in multiple sclerosis.  Research has shown that Wharton’s jelly from the umbilical cord may have features making it a better therapeutic alternative compared to bone marrow mesenchymal stem cells. So far, small studies have shown promise. Larger human trials are needed.
Reference
    1. Darlington, P.J., Stopnicki, B., Touil, T., Doucet, J.S., Fawaz L.,  Roberts, M.E., Boivin, M.N., Arbour, N., Freedman, M.S., Atkins, H.L., Bar-Or, A., Canadian MS/BST Study Group. Natural killer cells regulate Th17 cells after autologous hematopoietic stem cell transplantation for relapsing remitting Multiple Sclerosis. Front Immunol. 2018, 9:834
    2. Donders, R., Bogie, J.F.J., Ravanidis, S., Gervois, P., Vanheusden, M., Maree, R., Schrynemackers, M., Smeets, H.J.M., Pinxteren, J., Gijbels, K., Walbers, S., Mays, R.W., Deans, R., Van Den Bosch, L., Stinnissen, P., Lambrichts, I., Gyselaers, W., Hellings, N. Human Wharton’s jelly-derived stem cells display a distinct immunomodulatory and preregenerative transcriptional signature compared to bone marrow-derived stem cells. Stem Cells Dev. 2018, Jan. 27(2):65-84
    3. Bose G., Atkins, H.L., Bowman, M., Freedman, M.S. Autologous hematopoietic stem cell transplantation improves fatigue in multiple sclerosis. Mult. Scler. 2018, Sep: 1352458518802544 (epub: ahead of print)
    4. Sahraian, M.A., Mohyeddin Bonab, M., Baghbanian, S.M., Naser Moghadasi, A. Therapeutic use of intrathecal mesenchymal stem cells in patients with Multiple Sclerosis: a pilot study with booster injection. Immunol Invest 2018, Aug. 29:1-9
    5. Holloman, J.P., Ho, C.C., Huntley, J.L., Gallicano, G.I. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. Am. J. Stem Cells. 2013, Jun. 30, 2(2):95-107
    6. Nash, R.A., Hutton, G.J., Racke, M.K., Popat, U., Devine, S.M., Griffith, L.M., Muraro, P.A., openshaw, H., Savre, P.H., Stuve, O., Arnold, D.L., Spychala, M.E., McConville, K.C., Harris, K.M., Phippard, D., Georges, G.E., Wundes, A., Kraft, G.H., Bowen, J.D., High-dose immunosuppressive therapy and autologous hematopoeitic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3 year interim report. JAMA Neurol 2015, Feb. 72(2):159-69

This is for informational purposes only not medical advice see your physician.

Standard
multiple sclerosis

Ketogenic diet: can it play a role in treating symptoms of Multiple sclerosis?

Virginia Thornley, M.D., Neurologist, Epileptologist
September 19, 2018
@VThornleyMD
Introduction
Multiple sclerosis has no cure at this current moment. It is unclear what is the exact etiology otherwise there would be a cure. Based on research, genetic and environmental factors play a role. Based on MRI observations, there are inflammatory and degenerative components to the pathogenesis.
 
What is the ketogenic diet and how does it pertain the brain
The ketogenic diet was initially found to be effective in treatment of medically refractory seizures. But the underlying concept might be applied to other diseases as well.
Instead glucose as the energy substrate, ketones are utilized, If the supply of glucose is reduced, the energy source is shifted towards the beta-oxidation of fatty acids into ketone bodies. These ketones become the new source of energy and allows increased ATP formation which is the source of energy in the mitochondria, which is the powerhouse of the cell where energy is formed.
37608_434615273840_1627543_n
 
Different lines of thinking regarding pathogenesis of Multiple Sclerosis
There are lines of thought that Multiple sclerosis can be inflammatory versus neurodegenerative. Because of this many agents are directed towards the autoimmune component of the disease process. It is commonly thought that the autoimmune process results in the neurodegeneration seen on MRI.
As evidenced by the “black holes” seen on MRI after acute attacks, there is evidence there is a neurodegenerative aspect. This other line of thinking suggests that it is a degenerative process that triggers the inflammatory response.
It’s been found  that degenerating axons have abnormal mitochondria.
safe_image
Ketogenic diet and inflammation
In one animal study, it was found that the ketogenic diet reduced inflammatory cytokines after 14 days in animals (2).
 
Ketogenic diet and increased ATP
In one animal model with a control group and a group on ketogenic diet, after 3 weeks it was found that those on the ketogenic diet had a higher ATP/ADP ratio which is speculated to contribute towards neuronal stability.

How can the ketogenic diet help with Multiple Sclerosis?
The ketogenic diet reduces the formation of reactive oxygen species. It preserves ATP production when the mitochondria fails. The thought is that the axons start to degenerate once the mitochondria are dysfunctional (1).
In summary
There are no human clinical studies on ketogenic diet and the improvement of multiple sclerosis. Based on pre-clinical studies, there is indication that ketogenic diet may help improve the ATP stores when the mitochondria becomes dysfunctional which may potentially slow neurodegeneration of axons.
The ketogenic diet might reduce inflammation which is thought to be triggered by a neurodegenerative process in Multiple Sclerosis. However, more studies are needed especially human clinical trials. Currently there is not enough evidence to support this based on the available studies as pre-clinical studies do not always correlate in human trials. More studies are needed.

If you’re burned out reading this article check out  Medicine, The Musical brought to you by colleague Writer, Lyricist, Composer – Michael Ehrenreich, M.D. 

Just helping a colleague promote their dream.

Save the date for Medicine. The Musical
safe_image
 
Reference
  1. Storoni, M., Plant, G. The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis. Mult. Scler. Int. 2015. doi 10.1155/2015/681289
  2. Dupuis, N., Curatolo, N., Benoist, J.F., Auvin, S., Ketogenic diet exhibits anti-inflammatory properties. Epilepsia, 2015. 56(7):e95-98
  3. DeVivo, D.C., Leckie, M.P., Ferrendell, J.S., McDougal, D.B., Jr. Chronic ketosis and cerebral metabolism. Ann Neurol. 1978, Apr. 394):331-337
Standard
multiple sclerosis

Review of literature: can the Wahls diet (modified Paleolithic diet) and low saturated fat Swank diet have any effect on multiple sclerosis?

Virginia Thornley, M.D., Neurologist, Epileptologist

September 17, 2018

@VThornleyMD

Introduction

Patients are seeking complementary treatments aside from conventional agents. Agree with it or not, if doctors do not listen to their patients they will seek it elsewhere so it is good to be up to date on the review of literature. While alternative treatments are commonly lacking in evidence based medicine it does not necessarily have to work in opposition with conventional agents. There are studies by Mauskop, (1) a headache specialist who found that 50% of migraineurs are magnesium deficient and magnesium can be a effective preventative agent in selected patients. Instead of being instantly dismissive, review of the literature should be sought to have an evidence-based understanding from a scientific level.

What is the modified Paleolithic diet?

In the modified Paleolithic diet, there is stress on meat, fruit and vegetables, excluding legumes, dairy and grains (2). Night shade vegetables such as tomatoes and eggplants are excluded.

EFF112B6-3C70-4795-A919-F8ED5CA7B296

Save the date for Medicine. The Musical

What is the Swank diet?

Dr. Roy Swank from Norway hypothesized that a diet rich in saturated fat likely caused a faster progression of the disease state in multiple sclerosis relapsing-remitting type. He followed 144 patients for 34 years. The patients consumed less than 20g of saturated fat in their diet and followed. It was observed that the relapses and progression correlated with the amount of saturated fat that was consumed. The greatest benefits were seen in those with mild symptoms at the start of the study. The patients were followed 50 years, however, there were no case controls patients for comparision (3).

Review of literature of the Wahl’s diet on Multiple sclerosis

One study focusing mainly on the dietary component seeks to understand an effect using the randomized controlled clinical trial method. The study is ongoing (2). It seeks to study the anecdotal information that diet low in saturated fat may lessen  the debilitating symptom of fatigue in patients with multiple sclerosis. While there have been anecdotal data, many patients have been found to drop out of the control group because of poor tolerability making results unreliable (2). In addition, the studies available provide a multi-prong approach including factors of stress reduction, exercise and muscle stimulation.

4AB02EC5-BD66-419E-94FD-6DF9628C6B42

Multimodal approach: exercise, stress reduction, meditation, massage and diet

One small study of 20 patients demonstrated some benefits of modifying diet, reducing stress and stimulating muscles in relation to multiple sclerosis symptoms.  They found that patients who presented with mild symptoms of progressive multiple sclerosis received some benefit to a multi-prong approach with regard to gait improvement compared to those who were more advanced in their disorder (4).

In summary

To summarize, at present there is insufficient data to support the Wahl’s diet as an effective treatment option based on the available current studies.  However, having said that there has been some anecdotal and very small studies indicating benefits in multiple sclerosis. Randomized controlled clinical trials which are the gold standard in research are ongoing which will be shed more light on its effectiveness.

In the meantime, while there are no completed large randomized controlled clinical trials, these types of diets and modalities are complementary with the current treatment and would do no harm. However, until large randomized controlled clinical trials are completed, it is difficult to ascertain if they are indeed effective and recommend it advocating it as effective.

About

Introduction/Disclaimer

http://neurologybuzz.com

If you’re burned out reading this article check out  Medicine, The Musical brought to you by colleague Writer, Lyricist, Composer – Michael Ehrenreich, M.D. 

Just helping a colleague promote their dream.

Save the date for Medicine. The Musical

safe_image

 

Reference

  1. Mauskop, et al, All migraine patients should be treated with magnesium. Journ. Neural Trans. 2012, May, 119(5):575-579
  2. Wahls, T., Scott, M.O., Alshare, Z., Rubenstein, L. Darling, W., Carr, L., Smith, Chenard, C.A., LaRocca, N., Snetselaar. Dietary appraoches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: a study protocol for randomized controlled trial. Trial. 2018, Jun. 4, 19(1):309
  3. Swank, R.L., Duggan, B.B., Effect of low saturated fat diet in early and late cases of multiple ssclerosis. Lancet, 1990, Jul., 7, 336 (8706)
  4. Bisht, B., Darling, W., White, E.C., White, K.A., Shivapour, E.T., Zimmerman, M.B., Wahls, T. Effects of a multimodal intervention on gait and balance of subjects with multiple sclerosis: a prospective longitudinal pilot study. Degen. Neurol. Neuromuscul Dis. 2017, Jun. 26, 7:79-93

 

Standard
Amyotrophic lateral sclerosis, Epilepsy, Glaucoma, multiple sclerosis, pain, Parkinson's disaese, Peripheral neuropathy, Tumor

Medical marijuana: dispelling myths and fallacies behind cannabidiol and tetrahydrocannabinol

Virginia Thornley, M.D. Neurologist, Epileptologist

Introduction

The endocannabinoid system is found naturally in the brain. It is responsible for the sense of well-being one gets after running a 5-mile course. It does not work through endorphins or adrenaline, as some people may think. It works at the level of the endocannabinoid system. There is a community of CBD producers and consumers and it is in this mysterious world that it is well-known to be used in many medical conditions, still shunned by the majority of the medical community, Congress and even patients in general. The 2 most commonly known are cannabidiol and tetrahydrocannabinol. Cannabidiol has medical properties and has a weak affinity to the CB1 receptor which is predominantly found throughout the central nervous system, which is likely why it is found to work in numerous neurological conditions. Tetrahydrocannabinol (THC) is a well-known cannabinoid most notoriously known for the euphoria of kingpins seen on movies propagated by pop culture. Unfortunately, these connotations overshadow the well-known medicinal benefits. Cannabinoids have been used for centuries even in the B.C. period. It was part of the American pharmacopeia in the 1980’s until it was banned in the 1930’s. Slowly, these products are gaining popularity as a treatment for many medical conditions, primarily neurological because the CB1 receptor is so abundant in the nervous system, due to patients becoming more and more frustrated with the adverse effects and ineffectiveness of conventional treatments. In Europe, a combination of THC and CBD have been used in multiple sclerosis patients since 2010.  Animal studies and cell line culture studies demonstrate many potential mechanisms in which CB1 receptors, CBD and THC may be beneficial at the cellular level in many diseases, mechanisms are still being elucidated. It is most commonly used for chronic pain and epilepsy. As with any medication, it may or not be effective for everybody.

IMG_8359_preview

How it works–the nitty gritty

Cannabidiol has none of the psychoactive properties as THC. One needs 100 times the amount of CBD to have the same intoxication as THC. Therefore, it works well for those who are reluctant to go this route but who have found conventional medications which do not provide effectiveness, they are simply not cutting it. Because very little is know about its titration, medical marijuana can seem like entering into the world of an apothecary, or such as that found in the medieval days when potions are concocted. Physicians who use it in their treat it similar to a medication and the guidelines are similar start low and go slowly.  Tetrahydrocannabinol is more potent and at higher doses works more effectively for pain control and seizures. THC is used at relatively low concentrations in order to effect its medical properties, at higher concentrations one may run into side effects which offsets its medical value. There are different ratios of CBD:THC, different ratios correspond to different symptoms treated.  CBD is required in conjunction with THC in order to offset the potential side effects of THC. Tolerance does not build in the system such as that seen with opioids, although if one is medical marijuana naive, the lowest dose possible is ideal. There are no side effects of respiratory depression such as that seen with other medications for pain such as opioids.Consult with your treating physician.

Current legal state of affairs

Currently, there are many states that recognize the medical value of medical marijuana with medical marijuana laws allowing the opening of licensed dispensaries. However, the same cannot be said for the federal law.  In some states, the carrying of THC on your person can result in fines and imprisonment. Despite marijuana laws enacted, qualified physicians are at risk for being questioned by authorities, its recommendation and use is not for the faint of heart on the part of physicians and patients. Cannabidiol comes from hemp oil and is not considered illegal. However, anyone who even has 1% hemp oil in their product can still label that product as cannabidiol, which may be the reason why some patients are not getting the full medical effects when bought from the flea market or a vitamin store.  Tetrahydrocannabidiol which is more well-known for its recreational use and concomitant psychoactive properties at very high doses is federally illegal in many states. Many states often have registries so patients who require this may obtain an ID and verify they are under the care of a qualified physician. It can take a few months to obtain an ID because many patients are often at the end of their ropes in terms of effectiveness of medications. Many patients wish to come off opioids or do not like the idea of needing higher and higher pain medications for their chronic illnesses. It may serve as a great antidote for the current opioid crisis that is well-documented in the news or overdocumented in the news. Many mothers order products online from other countries to counteract the illegalities of their states in order to help their child who may be using 4 potent anti-epileptic agents and is now like a zombie because of the number of medications. While physicians are leery suggesting anything that is in category 1, its medical value cannot be disputed. There is too much evidence tipping it towards the other side of the scale. As tPA was in its infancy of use and physicians were hesitant using it due to its hemorrhagic adverse effect and is now the standard of care for stroke protocols, medical marijuana will likely find its way back into the pharmacopeia, the amount of medical evidence is far too compelling to ignore.

IMG_8793_preview

In conclusion

In short, when used wisely, cannabidiol is a non-intoxicating effective treatment for many medical conditions especially neurologic, as evidenced by thousands of years of history of its use and current animal models, clinical trials and wider clinical experience in Europe. When cannabidiol is combined with low concentrations of THC, the medical effect is even greater with the entourage effect without the stigmatized psychoactive effects that are usually associated with THC.

Introduction/Disclaimer

About

https://neurologybuzz.com/

Standard
multiple sclerosis

Sativex (tetrahydrocannabinol and cannabidiol) and the European experience in medically refractory spasticity in multiple sclerosis

Virginia Thornley, M.D., Neurologist, Epileptologist
March 12, 2018

Introduction

Sativex has been available in Europe since 2010. It is a combination of tetrahydrocannabinol and cannabidiol at a ratio of 1:1 and has been found to be effective in spasticity resistant to medications in patients with multiple sclerosis. Spasticity is the increased tone seen in the muscles due to abnormalities in the central nervous system such as the white matter lesions seen in multiple sclerosis.

Sativex and medically refractory spasticity in multiple sclerosis

Sativex is a THC:CBD (tetrahydrocannabinol:cannabidiol) preparation taken oromucosally which was approved in European countries for the treatment of medically refractory spasticity in patients with multiple sclerosis. Sativex contains a 1:1 ratio of THC to CBD, where THC interacts with CBD receptors to reduce spasticity while CBD ameliorates the side effects often seen with THC. In one large clinical trial of 1615 patients, 42% showed improvement of spasticity in the first 4 weeks, defined as > or = to 20% reduction in spasticity. The responders were double-blinded and grouped under placebo or THC:CBD, a larger proportion of patients had significant response compared to placebo, > or = to 30% reduction of NRS score for spasticity. 47% had adverse effects including fatigue and dizziness. Reported side effects included psychiatric disturbances, 55 had cognitive (attention problems, cognitive worsening and memory problems) and psychiatric issues (confusion, panic attacks, hallucinations, depression and suicidal ideations). Fatigue, drowsiness, dizziness, gastrointestinal symptoms, mouth discomfort and allergic reactions were other reported side effects. There was no evidence of abuse or addiction in the patients. There were significant side effects deemed unrelated to Sativex including, myocardial infarct, hypertensive crisis (2).

In the original MOVE 2 trial in Italy, in the 322 patients studied, the NRS numerical rating scale decreased by -19.1% from baseline time to 3 months of treatment with Sativex. At visit 3 at 3 months, 24.6% were considered relevant responders to the medication with 30% or more reduction in spasticity. Side effects of >1% included somnolence, dizziness, and fatigue. 41 patients reported side effects 3 were serious side effects of which one was not related (3).

IMG_5833_preview

Sativex and studies in Germany, United Kingdom, Switzerland and Spain

Sativex was first approved in Spain and the United Kingdom in 2010 for use in spasticity related to multiple sclerosis. Data were collected to study continued efficacy and safety profiles.  941 patients (761 from the UK, 178 from Germany and 2 from Switzerland) were studied. Data was collected up until January of 2015.  A patient registry was set up as per guidelines before new medications are approved. Patients from the UK were 22% of the patients registered in the UK using that medication since 2010. Continuation rates were 1 year for 68% of patients. Among those who stopped it, 30% cited lack of effectiveness and 25% described side effects. Some significant side effects include suicidality in 2% and depression in 6%. There was no evidence of abuse, addiction or misuse. The fatigue was within the known safety margins of the drug. The patients used on average 5.9 +/- 4.9 sprays per day

In Spain, 204 patients were evaluated. After 6 months, 143 (70.1%) had benefited from using it for spasticity. After 12 months 64.7% derived beneficial effects. The average dose was 6.6 sprays a day. 41 patients had side effects consisting of psychiatric events, falls, reduced the ability to drive and others. Both study groups in the UK, Germany, Switzerland and in Spain both derived benefits justifying continued used of Sativex. Adverse effects were low, and the mean use of sprays was between 5.9-6.6 which was lower than the clinical trial using 8 sprays (4).

Sativex and timeline when it is found to be ineffective

In one large study in Italy involving 30 multiple sclerosis centers, the discontinuation profile was studied. Patient data from 30 MS centers were collected from a period of January 2014 to January 2015. 39.5% of patients disconnected treatment with Sativex. Spasticity was studied using the EDSS or expanded disability status scale and the patient NRS numerical rating scale 0-10 for spasticity. Information was collected at baseline (T0), 4 weeks (T1), 3 months (T2) and 6 months (T3).

Spasticity was noted in 1615 patients. 1597 (39.5%) discontinued treatment. Of those, 24.8% did not reach 20% effectiveness using the NRS scale. Reasons of discontinuing include lack of effectiveness 23%, side effects 16.3% and lack of compliance 0.8%, lost to follow-up 0.4%, patient choice 0.3% and unknown reasons 2%. Analysis showed that an increase in the NRS scale by 1 point at baseline time corresponded to a lower rate of discontinuation. While an increase in the NRS scale at timeline 2 or at 4 weeks corresponded with worsening spasticity and a higher non-responder rate. They concluded that Sativex is a good option for spasticity and by 4-6 weeks, patients can be reliably identified as responders or non-responders to avoid the cost burden on the healthcare system (1).

german tripand old pics 410_preview

 

https://neurologybuzz.com/

Introduction/Disclaimer

About

Reference

  1. Messina, et al, “Sativex in resistant multiple sclerosis spasticity: discontinuation study in a large population of Italian patients (SA.FE. study), Public Library of Science PLoS One, 2017, 12(8) e0180651
  2. Patti, et al, “Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity,” Journal of Neurology, Neurosurgery and Psychiatry, 2016, Sep., 87(9):944-951.
  3. Trojano, et al, “Effectiveness and tolerability of THC/CBD oromucosal spray for multiple sclerosis spasticity in Italy: first data from a large observational study,” European Neurology, 2015, 74:178-185,https://doi.org/10.1159/000441819
  4. Fernandez, et al, “THC:CBD in daily practice: available data from UK, Germany and Spain,”European Neurology, 2016, 75 (supp 1);1-3, https://doi.org/10.1159/000444234
Standard
multiple sclerosis

Multiple sclerosis: stem cell therapy and its role in remyelination

Virginia Thornley, M.D., Neurologist

February 25, 2018

Stem cell research is a fast-growing arm of science. Multiple sclerosis is an autoimmune disease where the central nervous system is attacked as foreign. Clinical symptoms depend on the area involved, primarily in the white matter. Scientific research is being more and more directed towards agents and treatment modalities that differ from today’s immunomodulating agents given the potentially devastating side effects of the more efficacious medications. The heavy hitters tend to be more serious adverse effects.

How stem cell administration works

Umbilical cord mesenchymal stem cells may play a significant role in tissue repair and immunomodulatory processes that are important in multiple sclerosis. Stem cells divide into different types of cells which give rise to different tissues. They hold a wealth of potential in repairing damaged tissue as that found in multiple sclerosis. In one study, the mesenchymal stem cells from the umbilical cord were found with low immunogenicity. They can inhibit the multiplication of killer cells, T lymphocytes, and B lymphocytes and can inhibit the maturation of dendritic cells. Mesenchymal stem cells migrate to the site of injury and proliferate to repair damaged tissue.

Different stem cells that can be used in multiple sclerosis

Other types of stem cells are derived from hematopoeitic, embryonic, neural, spermatogonic, adipose, endometrial, Wharton jelly surrounding the umbilical cord and pluripotent-induced stem cells.

13925802_10154408561258841_5096074368744450311_o

Stem cell administration in 2 patients and reduction of abnormal MRI abnormalities

In one study, 2 patients were treated with stem cells. Clinical symptoms were reduced in the 1st patient, they were followed 8 years and found without adverse effects. The 2nd patient progressed and the timing of stem cell administration was shortened resulting in the reduction of symptoms. The number of abnormal foci seen in the MRI of the brain was less suggesting remyelination of damaged tissue within the brain. During illness, the body increases the immunogenicity with amplification of inhibitory co-stimulatory signals. With stem cell administration, this process reduces these destructive immune processes. Umbilical cord mesenchymal cells were found to inhibit IL-17c, HLA-DRB1, and IL-2 thereby protecting against an autoimmune response. The mechanism of action by which the stem cells work favors a remyelination repairing the damaged area(1).

Stem cell research in a study of 20 patients and reduction in disability

In another larger study of 20 patients, mesenchymal stem cell neural progenitor was applied. Results showed 70% had improved muscle strength and 50% improved in bladder symptoms. Improved EDSS (Expanded Disability Status Scale) was noted in 40% of patients, there were some minor adverse effects (2).

13680208_10154408585938841_6912978101643468976_o

Larger clinical randomized case control trials are needed.

References
  1. Meng, et al, “Umbilical cord mesenchymal stem cell transplantation in the treatment of multiple sclerosis,” American Journal of Translational Research, 2018, 10(1): 212-223.
  2. Harris, et al, “Phase I trial of intrathecal mesenchymal stem cell-derived neural progenitors in progressive multiple sclerosis,” EBioMedicine, 2018, Feb., pii.S2352-3964 (18)30051-3 (Epub ahead of print)
Standard