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Tyler Bradford

Caroline Reynolds

ENG 1201

10 April, 2022

The Next Frontier in Multiple Sclerosis Research

When I was younger, only fourteen at the time, my family received the detrimental news

that my mom had been diagnosed with Multiple Sclerosis (MS). At the time, the concept of the

disease and all that it entails was very foreign to me. Since then, however, I have been engrossed

in the process of learning all I can about the field of MS research scientists, as well as, more

importantly, the disease itself. My mom’s diagnosis was the first rotation that propelled me

forward in my desire to be an MS research scientist one day, and began my hopes of making a

difference in a field that carries such meaning to me. In theory, Multiple Sclerosis is simply

understood, but as usually holds true, the disease is much more complicated than one would

think. MS is a chronic disease in which the body’s immune system attacks certain parts of the

brain and spinal cord. Many treatments have been pushed through the pipeline in an attempt to

cure this disease, including stem cell therapy which will soon be the most effective treatment due

to its many capabilities: it can manipulate cells that repair other cells, “reboot” the immune

system, directly insert myelin sheath cells to protect nerve cells and countless other functions

which prove this therapy is making great bounds towards the cessation of this disease. This paper

will explain stem cell therapy and why it is likely to be the best treatment option in the future.
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Fig. 1. This diagram shows the location of myelin sheaths and what they look like
when they are functional and when they are destroyed (Blueringmedia).

Multiple Sclerosis first appeared in its early developments around the 1300’s but wasn’t

given a proper name until 1868 wherein it was coined by Jean-Martin Charcot. MS occurs when

there are lesions in the brain and spine, which are areas of damage/scarring due to the immune

system attacking the myelin casing around an axon (the electric signaler and carrier of a neuron).

There are many forms of MS, one of which is Relapsing Remitting Multiple Sclerosis or RRMS.

This is the most common form of MS and is somewhat unpredictable. This type of MS occurs

when someone has neurological symptoms and they usually fluctuate between remissions

(recovery) and the attacks. This version is problematic because if someone is in remission, it is

hard to tell if they are cured forever or if they will have another attack at some point in their life.

Another form of MS is Secondary Progressive MS (SPMS). This occurs when lesions increase

and neurological function decreases. This category of MS is dangerous because it means the

body is contiuing to deteriorate. The last version is Primary Progressive MS (PPMS). This is
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relatively the same as SPMS but if there haven’t been any previous lesions or attacks. One reason

why MS is such a dangerous disease is because of the plethora of symptoms that come along

with the disease. These symptoms, more often than not, have a very negative effect on one’s life.

Some of these symptoms include issues with eyesight, fatigue, numbness, tingling, migraines,

joint pain, sensitivity to heat, brain foggy-ness, incontinence and more. People with MS are

directly affected by these more because the disease of MS is the direct attacker of these myelin

sheaths that causes these symptoms. Migraines and joint pain are good indicators that one should

get tested for MS, especially if it runs in their family. A less conventional, yet very pressing issue

that occurs with MS is the effect it has on someone’s social life. When you have fatigue and

migraines it is hard to also have the energy to still do things with your friends and coworkers. We

have come a long way though in terms of medicine for this disease. In the eighteen and nineteen

hundreds, many treatments for MS were tested, such as; mercury, malaria parasites, arsenic and

nightshade. The first some-what reliable medication was cortisone which came out in 1951, but it

didn’t have long term lasting effects. Today, there are many good and lasting treatments for MS,

and it is a livable disease. Hopefully in the near future, we will be able to completely cure people

with this disease.

This disease affects about one million Americans. My mom, as mentioned before, is one

of those people. Her disease has greatly influenced my involvement and interest in this field.

This is her story and journey through this illness. In July 2018, she started getting extremely bad

headaches. These headaches continued to get worse and worse until they were overwhelming.

She had excruciating migraines almost every single day for almost six months straight. She could

also feel her hands, arms, and legs getting weaker. On top of all of that she was very tired. She

describes it as “more tired than when you’re pregnant and that is the most tired you will ever
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feel, and it was worse than that”. She recalls having to stop at stop lights throughout the day

because she would be so tired, and she is not a weak or weak minded person in the slightest so

this is very extreme. She finally went to her family doctor and he ultimately sent her to three

neurologists. The first two didn’t take her seriously and ignored her symptoms, which only

delayed her getting the treatment she needed as fast as she could. After she found a good doctor,

he gave her an MRI and it turned out she had a brain and spinal lesion. Finally she got a spinal

tap, which is when they remove spinal fluid from your back to help more accurately diagnose

you. It turns out she had both MS and Intracranial Hypertension. Intracranial Hypertension is

when you have too much fluid on your brain and it acts as a false tumor. This condition is also

known as Pseudotumor and the excess fluid has to be removed through the spinal tap. After the

spinal tap and thirteen months after the onset of her symptoms, she was diagnosed with MS in

August of 2019. She was then put on a medicine called Tecfidera, which is a twice a day pill that

dramatically lowers the immune system in order to slow down the progression of MS by taking

out the B cells, but it sacrifices the rest of your immune system as well. This however didn’t last

long because even with this medicine she was still developing more lesions and worse

symptoms. She was then switched to Ocrevus, which is an infusion she receives twice a year.

This medicine is stronger and is intended to raise her immune system by only attacking her B

cells rather than her whole immune system, although that has not happened yet and she’s been on

the Ocrevus for almost a year. She has also lost weight and gotten more in shape because it is

proven to help in the long run of people with MS. Ultimately, she is doing a lot better and living

a full and meaningful life. When asked if, given more research, she would be open to

remyelination stem cell therapy, she said she would if it was more researched, proven to be safe,

and worked better than what she was on now. Lucky for her, that horizon is quickly approaching.
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Many scientists agree that MS research is a rapidly changing field with a very bright

future. As Benjamin Segal, the director of the Neuroscience Research Institute, once said in an

interview last year, “Over the last 20 years, there has been a revolution in drugs that change the

course of (MS)”. The scientific community concerned about MS has two primary paths:

remyelination and repair, and treating Secondary Progressive MS (SPMS). Remyelination and

repair is a subfield which focuses on creating ways to repair the myelin structures that insulate

the nerves on the spine, which are attacked by the body in people with MS. Treating SPMS

focuses on slowing and preventing the further progression of MS within patients. Repair will

soon be the best way of treating this disease with the help of stem cell research.

While stem cell research isn’t very reliable or well understood at this time, it will soon be

the most useful tool in treating and curing MS. There are many different types of stem cells that

can be utilized by scientists in different therapies such as, hematopoietic, mesenchymal, neural,

human embryonic, and induced pluripotent stem cells. Hematopoietic stem cells have the ability

to transform into any type of blood cell. Mesenchymal stem cells have the ability to inform other

stem cells what to turn into. Neural stem cells have the ability to become neurons and glial cells.

Embryonic stem cells and induced pluripotent stem cells can both turn into any cell type, but this

is one of the harder treatments currently because of the many possibilities for this cell type. The

most well researched of these, in terms of regenerative capabilities, are the mesenchymal stem

cells (MSCs). One of the functions of this kind of cell is that it tells other stem cells when and

where to repair myelin. This is one of the core concepts for the future of MS research and the

hope that so many have been waiting for. From what we know now, Mesenchymal Stem Cells

are scientists’ best chance at reversing the effects of MS. MSCs will allow scientists to reverse

the damage done to nerves and the destroyed myelin sheaths. This technology, when further
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researched, will fuel the next scientific revolution and bring a new wave of cures to many

different diseases. In MS, this technology will be able to be used to fix the problem as a whole

and with enough research, cure it. There are other ways to use stem cells as well until that

technology is available.

Fig. 2. This is a visual graphic showing what the different types of stem cells look like.

Another very important form of stem cell therapy is hematopoietic stem cells (HSCs).

These stem cells do a different job than MSCs, HSCs focus on anti-inflammatory benefits. These

cells give rise to all blood cells including the immune system. An HSC transplant is an

anti-inflammatory therapy which is more effective than most drugs and takes place in three

stages. First, the mobilization and harvesting phase. During this stage HSCs are taken from the

bone marrow of an individual and then frozen for later. Next is the conditioning phase. This stage

is a chemotherapy that kills all of the negative MS immune cells, this is risky however because
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of the nature of chemotherapy. The final phase is readministration. During this phase the frozen

HSCs are reintroduced to the blood and the hope is that the cells and immune system will

develop correctly and without MS. This therapy has been proven to work many times over and is

already a reliable short-to-mid-term solution. There are reasons why it is not a cure yet though,

for example it costs $150,000 for the therapy and you must undergo chemotherapy which comes

with a laundry list of side effects and risks. For now though, it is the best stem cell therapy we

have.

The most far off but most revolutionary therapy is embryonic stem cell therapy. This

therapy will eventually allow scientists to cure any degenerative disease. For MS, this means

being able to insert these cells and having them programmed to become Myelin Sheaths for the

nerve cells. The hardest part of developing this therapy is the fact that, since embryonic stem

cells can become any cell, it is hard to program it and be sure of exactly how it will develop. But

with more and more research coming out all the time for this field and topic, it is not impractical

to be looking for a cure to MS in the next couple decades.

There are many drugs and infusions out today that work at slowing progression of MS.

Ocrevus is one of the biggest and most well-known MS drug treatments on the market. Ocrevus

is an infusion that is distributed into the vein of the recipient. It is “a humanized monoclonal

antibody that targets CD20 positive B lymphocytes” as put by the National MS Society. Ocrevus

is approved by the FDA for a multitude of uses including to treat RRMS and SPMS. Many of

these drugs are reliable and have relatively low risk. However, when the stem cell treatments

have more time and research behind them, they will make the drugs and therapies we have now

obsolete.
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Fig 3. This diagram shows how Ocrevus works and where it focuses in the body.
(Getonwithlife.co.nz).

Some may argue that if the drugs now work, then why not just stick with them and forget

about the stem cell therapies because of the ethical, dangerous, and applicable complications it

raises. Firstly, if you cast the politics aside, stem cell therapy is the future of medicine and the

stigma behind it should be discarded. Second, there is always risk when trying to manipulate

nature. This has been apparent since the dawn of medicine. However, the difference now is that

scientists can more accurately predict the risk level of treatments they develop and therefore be

more prepared for short-comings. In addition, our technology is becoming increasingly more

advanced and ready for these types of undertakings. Scientists try their best to be as safe as
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possible, and with guidance from organizations like the Food and Drug Administration (FDA)

they can develop new cures and treatments with safety as the number one priority. Lastly, the

applicable challenges of stem cell therapies are only limited by our technology, not by theory.

This means that once the technology required for this idea is created, it will be easy to apply on a

large scale. Stem Cell therapies will without a doubt be the future of medicine given that society

allows us to go down this path of scientific exploration. And isn’t blinded by its own short

sightedness.

As we’ve seen with the COVID-19 vaccines, previously researched technology can be

replicated to address specific disease. The COVID-19 vaccine was being researched for decades

prior to COVID-19. When scientists realized they could use the mRNA technology and code for

COVID-specific proteins, the possibility for further tweaking of the mRNA vaccine was

discovered. This may be a potential cure for anything from HIV - testing and trials are currently

underway - to breast cancer. There is no reason to doubt that with the proper investment into the

technologies available, that stem cell research can have a similar positive effect in the medical

community. If stem cell therapy is proven to be effective for MS, it may also apply to multiple

other auto-immune diseases, such as: celiac disease or rheumatoid arthritis. We need to use all of

the tools in our arsenal to advance medical technology. As is indicated in the COVID-19 vaccine

research, we can apply these principles to other therapies to find results.

Research indicates that mRNA vaccines and stem cell therapies can work together to halt

and possibly reverse disease. The mRNA technology can tell the immune system not to attach

the myelin sheath, while the stem cell therapies can be programmed to reverse the damage from

the previous attacks on the myelin sheath. Without proper investment into these technologies, we
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will not be able to unlock the possibilities of MS disease progression, in addition to the other

diseases that this type of technology could combat.

Throughout history, there have been discussions about the ethical employment of

scientific technologies. We have moved through these arguments as science has progressed. The

truth of the matter is that if you have taken tylenol, ibuprofen, or allergy medicine, you have

utilized a drug that benefitted from embryonic cell research. This will likely always be a point of

contention within the scientific community and society as a whole. We would benefit from

listening to the scientific and medical ethics professionals, who give their careers to studying and

reviewing the ethical impact of various scientific therapies and strategies.

All of this research I have conducted makes me very excited about the possibilities of the

future and for a cure for MS. As Stem cell therapy continues to improve our ability and

effectiveness at treating diseases like MS will increase as well. With a combination of rebooting

the immune system, controlling the repair cells within the body, and directly applying cells to

designated areas of the body, stem cell therapy will change the way we approach disease and will

allow us to cure diseases like MS.

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Work Cited

Fig 1. Blueringmedia. “Diagram showing multiple sclerosis concept illustration”. 123RF,

https://123rf.com/photo_59362260_diagram-showing-multiple-sclerosis-concept-illustrat

ion.html

Fig. 2. Facebook.com/bioinformantworldwide. “Do You Know the 5 Types of Stem Cells?”

BioInformant, 12 Mar. 2022, https://bioinformant.com/types-of-stem-cells/

Fig. 3. Getonwithlife.co.zn. “How does ocrevus work”. 2021.

https://getonwithlife.co.nz/about-ocrevus/how-does-ocrevus-work/

“Ocrevus.” National Multiple Sclerosis Society,

https://www.nationalmssociety.org/Treating-MS/Medications/Ocrevus.

“OCREVUS Reviews & Ratings.” Drugs.com,

https://www.drugs.com/comments/ocrelizumab/ocrevus.html.

Rosalind C. Kalb, MD. Multiple Sclerosis : The Questions You Have, The Answers You Need.

Demos Health, 2011. EBSCOhost,

https://search.ebscohost.com/login.aspx?direct=true&db=nlebk&AN=413390&site=eds-l

ive.

“Secondary Progressive MS (SPMS).” National Multiple Sclerosis Society,

https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progressive-MS
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Segal, Benjamin. “On the Horizon: The Future of Ms Treatments.” WebMD, WebMD, 13 Oct.

2021,

https://www.webmd.com/multiple-sclerosis/rms-perspectives-21/ms-next-in-treatment.

“Stem Cells in Ms.” National Multiple Sclerosis Society, 4 Nov. 2021,

https://www.nationalmssociety.org/Research/Research-News-Progress/Stem-Cells-in-MS

“Types of Ms.” National Multiple Sclerosis Society,

https://www.nationalmssociety.org/What-is-MS/Types-of-MS#:~:text=Four%20disease%

20courses%20have%20been,secondary%20progressive%20MS%20(SPMS).