September 20, 2020

The Niche

Knoepfler lab stem cell blog

A no B.S. guide to stem cells for Multiple Sclerosis (MS)

Symptoms of multiple sclerosis
Symptoms of multiple sclerosis.

Today’s post is my no-B.S. guide to the possibility of stem cells being used to treat Multiple Sclerosis (MS).

There is a great deal of buzz about using stem cells to treat or even cure multiple sclerosis.

How much of this stem cell buzz is real hope and how much is hype?

MS has a host of symptoms (see illustration at left from Wikipedia).

For many patients, conventional chemical medicines do a reasonable job managing the disease. However, for others the disease relapses, is unacceptably resistant to treatment, or the medicines have severe side effects.

New, safer and more effective therapies are desperately needed for multiple sclerosis.

The specific potential of stem cells for treating patients with MS is exciting and gives hope, but realistically there is tons of hype.

I know a lot of people with MS and many more contact me with generally the same question: can stem cells treat or cure MS today?

My best answer is “Maybe someday that will happen and I am hopeful, but that day is not today and it won’t even be this year or next.”

The most commonly sold stem cell intervention for MS at present involves IV injection of mesenchymal stem cells (MSCs) from either fat or marrow. Many times the MSCs are propagated in a lab prior to the transplant.

Below I outline the key issues and challenges with using stem cells today to treat multiple sclerosis.

To grow or not to grow? One of the most important issues in the arena of using stem cells to treat MS is whether (A) to use straight, non-manipulated stem cells that are freshly harvested or (B) to grow the cells in culture first to greatly increase their numbers. The advantage of (A) is that the less manipulation there is the fewer regulatory hurdles one is likely to face, although non-homologous use plays in here even if the cells are not grown. The disadvantage of (A) is that you may have only a few million true stem cells in the mix and that is thought, even by most experts in the for-profit clinic field that I have talked with, to simply be not enough to make any meaningful difference. Think drop in the bucket, or perhaps more like a drop in an ocean of the human body. The advantage of (B) addresses this issue. If via growth you can give a patient a billion rather than a million stem cells, you might have a profoundly more powerful therapy. However, the big problem for clinics is that growth in culture makes stem cells a drug subject to more practically challenging and expensive FDA regulatory oversight due to safety concerns.

Getting stem cells into the CNS. One of the challenges of treating MS with stem cells is that it is a disease of the central nervous system (CNS) meaning the brain and spinal cord. As it turns out the brain and spinal cord are protected from the rest of the body by the blood-brain barrier and cerebrospinal fluid blood barrier (let’s call them collectively the “BBB”). The BBB is vitally important because our bodies need to keep many things out of the brain and spine so that we can remain healthy. This potentially neurotoxic “stuff” that is excluded from the CNS can include outright toxins, chemicals that might change brain function, and pathogens like viruses and bacteria.

Without the BBB we all die.

However, the BBB makes it therapeutically challenging if not impossible to treat neurological disorders such as multiple sclerosis, autism, Parkinson’s, Huntington’s, and others with cellular therapies administered by IV injection. Cells are huge compared to many of the small molecules that the BBB filters out.

How exactly do you get cellular medicines into the CNS to treat such diseases if the BBB is in the way?

The answer is that you don’t get stem cells into the CNS via IV injection. (Update: it should be noted that in some disease states the BBB is somewhat compromised and some cells may more readily enter the CNS than usual. Also, although the evidence that MSCs can cross the BBB is very limited, other types of cells such as human cord blood cells may have higher intrinsic potential to enter the human CNS from the bloodstream. However, even in this case, the published evidence is very limited at this time.)

Often IV injection of even traditional chemical “pill” medicines into the bloodstream or ingestion of such medicines won’t work for CNS disorders because the BBB keeps them out, sometimes even super tiny molecules.

Therefore, you can imagine relatively huge things such as stem cells just do not make it across the BBB. That is literally like trying to push an elephant through the tiny holes in your colander. Maybe sometimes one strand of spaghetti will hang out part way through a hole in a colander after being drained, but not even the tip of an elephant’s trunk can fit, let alone the whole animal.

So what can be done to get stem cells into the CNS?

Some legit proposed stem cell therapies for CNS disorders interestingly invoke direct injection of the cells into the brain itself. I just saw a talk on this recently and it works to get cells into the CNS. A small hole is bored in the skull and a very fine needle is inserted via a device that can pinpoint the location of the injection of the cells. Fortunately, you usually don’t see for-profit clinics offering to inject stem cells into people’s brains. They go the IV approach instead almost 100% of the time, although some do sell high risk intra-thecal (spinal) injections of stem cells.

What this all means is that the clinics selling IV stem cell transplants for treatments of MS are either (A) selling a load of BS that the stem cells can get into the brain from the blood and do good stuff or (B) have to invoke a different theory that IV injections of stem cells do good things to the CNS indirectly.

Let’s talk more about the latter (B) option.

Helping Multiple Sclerosis indirectly via immunomodulation?  What good things could stem cells do for MS indirectly via that (B) option above and how would that work?

The idea is generally based on the fact that MS is an immunological disorder. The body attacks its own nerves in the CNS, damaging or destroying them. Stem cell clinics pitch the idea that injecting say a billion stem cells into the blood stream via a vein could help MS indirectly through immunomodulation, meaning calming down the immune system in general. In other words, they claim that by flooding a bunch of stem cells into the blood stream the patient’s general immune system activity will be lowered and that in turn will help MS by lessening autoimmune attacks on the nerves even if not a single cell makes its way into the CNS. It’s a good idea in theory, but in practice I’m not convinced that there is much evidence to support it actually working as an MS treatment today.

What are the issues with this potential approach?

A hit-and-run medicinal effect for the diseased CNS of MS? Unfortunately, in fact, there are some big problems with this indirect idea. First, stem cells from fat or bone marrow are not supposed to be floating around willy-nilly in the blood stream and your body knows this. As a result, your body filters all these stem cells out, mostly in the lungs (where potentially life threatening pulmonary emboli can form), and kills nearly all of them within hours. Autopsy studies of patients who received stem cell transplants of this kind show that essentially zero stem cells “engraft” (meaning stably find a home and survive) within the human body for years. Katarina LeBlanc’s lab published an incredibly important paper on this that you can find here. I highly recommend reading it.

What this means is that for IV administered stem cell transplants to help MS patients, they must within a period of hours (or at most a few days) have a powerful, helpful, and lasting effect on your body’s immune system. In science this is called a “hit-and-run” mechanism.

Even if we assume for the moment that the transplanted stem cells do indeed have a clinically meaningful calming effect on the immune system in MS patients that still is not enough by itself. This effect must last for years to help MS patients, who cannot get stem cell injections running $10K-$20K a pop every few weeks, right? That is impractical and would greatly increase the risks of side effects to patients.

The bottom line is that today there is no compelling scientific or medical evidence that IV stem cell transplants of this kind can help MS patients.

If providers here in the US  or those in foreign clinics such as in Panama or elsewhere selling this kind of therapy truly believe that these therapies work, they owe it to patients and to the stem cell community to collect data and publish it in journals or an online database.

Anecdotal evidence or testimonials won’t cut it. Show us all in the stem cell community real data.

Designer stem cells. One area that has promise, but will take as much as a decade or more to realize, is the production and use of designer stem cells that might treat MS. What do I mean by “designer stem cells”? These laboratory-produced stem cells would be made to secrete either the same stuff that stem cells naturally make but to a greatly increased extent (think 100,000 fold higher) or to secrete man-made medicines that are helpful for MS. Another idea is to make stem cells that are sneaky and somehow do not get eliminated by the body so they can hang around and do good stuff long term or sneak past the BBB.

In these kinds of ways, designer stem cells injected IV or directly into the brain might effectively help MS. It’s almost like a doctor being able to go inside your body and your CNS in this case and treat it from the inside out. However, this comes with associated elevated risks. Designer stem cells would almost certainly have a much higher risk of causing side effects such as cancer.

Bottom line. Stem cells have very important, real promise for Multiple Sclerosis in the long run as in the coming decades, but the science today does not support their use now in the ways that non-compliant or foreign stem cell clinics are selling them.

The risks from stem cell interventions for MS today such as infection, cancer, pulmonary embolism, and worsening of immune symptoms just to name a few are simply too high to justify the clinics selling a therapy that has no proven benefit.

I realize there are many people with multiple sclerosis who are suffering and for whom today’s conventional medicine has too little to offer, but at least for now I believe that stem cells are not the answer. To be clear, I do not judge patients who get such treatments. Rather, I worry about them in terms of their safety and their being exploited by people who in most cases are just after their money.

I’m critical of the not-read-for-prime time technology and the people selling it today, not the patients who are their targets.

Note: This post is not medical advice. I am not a medical doctor and all medical decisions should be made with your own physicians. This post is for general educational purposes on multiple sclerosis only.

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