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Stem cell treatments may offer hope to MS patients

By Dr. Ben Thrower
The management of MS has advanced rapidly during the past few decades. In 1992, there were no FDA-approved therapies for MS. In 2015, we have 13 approved treatments for altering the course of MS. Unfortunately, gaps in our knowledge remain. We have no approved options for progressive forms of MS and for many, the current treatment options are not enough to completely stop the course of their MS. Could stem cells be the magic bullet we are looking for? What types of stem cell treatments are there? Do stem cells have the potential to reverse disability? In this article we will look at hematopoietic stem cell transplants, mesenchymal stem cells and for-profit stem cell clinics in the U.S. and abroad.

MS is an autoimmune disease resulting from complex interactions between genetic and environmental factors, resulting in an immune attack that destroys myelin and the underlying axons themselves. Like other autoimmune diseases, including rheumatoid arthritis and systemic lupus, MS represents an immune system gone awry. As noted, there are 13 FDA-approved disease-modifying therapies. For some people with MS, these therapies may be quite effective in slowing the progression of disability, decreasing relapse frequency and helping prevent new MRI lesions. Our current treatments are not always effective enough for some people, however.

Host vs donor

What if we could “reboot” the immune system of the person with MS and give them an immune system that does not attack myelin? Sometimes this happens during the course of treatment of another health problem like certain cancers. During the treatment of some cancers, bone marrow transplants are used. These are typically allogeneic transplants, meaning that the stem cells used for the transplant come from someone other than the patient. This is typically a brother, sister, or an unrelated donor who is matched as closely as possible. Cells from umbilical cord blood can also be used. Once the cells from the donor are harvested, the recipient is treated with high doses of chemotherapy to kill any cancer. This chemotherapy also wipes out the recipients existing immune system The donor cells are then given to the recipient by vein and a new immune system is generated in the bone marrow. This new immune system is essentially that of the donor and not the recipient. The person with MS who gets an allogeneic bone marrow transplant to treat their cancer may have added benefit of treating their MS as well. They have been given a new immune system, one that does not attack myelin. Obviously, this is not the way we want to resort to treating MS. Allogeneic stem cell transplants require the long-term use of drugs to help prevent a war between the new immune system and the recipient. When the new immune system attacks the recipient, we call that graft versus host disease. When the recipient’s remaining immune system attacks the new immune system, we call that host versus graft disease. In addition to these complications, there is the risk of serious infections due to immune suppression from the initial high-dose chemotherapy, or the long-term lower dose immune suppressant drugs.

This brings us to a procedure called autologous hematopoietic stem cell transplantation or HSCT for MS. In contrast to the allogeneic stem cells from another individual, autologous stem cells come from the patient’s own bone marrow. There are several advantages. No donor needs to be identified and there is no risk of graft versus host or host versus graft disease. This eliminates the need for long-term immune suppressant drugs. There are still, however, the risks associated with the high-dose chemotherapeutic agents used in the initial shut down (immune ablation) of the immune system.

When other routes fail

So, what are the steps during HSCT? The person with MS would have autologous stem cells taken from their blood or bone marrow. Sometimes, drugs are given to help the body produce more stem cells prior to their harvesting. After the cells are harvested, they are then frozen for later use. The person with MS is then given the chemotherapy drugs that will hopefully wipe out the existing immune system. Once this is done, the autologous stem cells are given back via a blood transfusion so that a new immune system, one that will not attack myelin, can grow. This process may take several weeks. During this time, the patient may be prone to serious and even life-threatening infections.

How effective is HSCT in stopping MS progression? In 2015, results of the HALT-MS trial using HSCT in 24 people with relapsing-remitting MS were reported. These individuals had all failed prior conventional therapies. Three years after HSCT, 91 percent of the patients had no progression of disability and 86 percent had no relapses. Modest improvements were seen in disability and quality of life. This study is ongoing and results will be published at four and five years.

A second HSCT study looked at 145 people with MS with a mixture of relapsing-remitting and secondary progressive MS. As a group, disability improved over four years. Further analysis showed that the improvements in disability were limited to those with relapsing-remitting MS and an MS diagnosis for less than 10 years.

HSCT appears to be an effective treatment option for aggressive relapsing forms of MS. This remains a complex procedure with some risk for serious side effects and should only be considered when more traditional therapies have failed. Unfortunately, HSCT does not appear to be especially effective in progressive forms of MS. This may be because of more severe tissue damage in the brain and spinal cord of people with progressive forms of MS. Alternatively, it may be that the immune system sends inflammatory cells into the brain and spinal cord that are difficult for the chemotherapeutic agents to reach and kill.

Mesenchymal migration

Let’s take a look at other types of stem cells that may be of benefit in MS. Embryonic stem cells were once a hot topic, but the focus now seems to have shifted to mesenchymal stem cells. Embryonic stem cells are called totipotent, meaning they have the potential to develop into any tissue in the human body. This may be both a blessing and a curse. Once released into a patient, embryonic stem cells have the potential to repair, but also have the potential to become cancerous or develop into other unwanted tissues. Add to that the ethical concerns about embryonic stem cells expressed by some and we have seen the shift towards mesenchymal stem cells.

Mesenchymal stem cells can be isolated from the blood, bone marrow or umbilical cord blood. These cells appear to play a vital role in immune regulation and the promotion of tissue repair. Injected into the blood stream, these cells may be able to migrate to areas, such as the brain and spinal column in the person with MS, where repair is needed. These cells are being looked at to treat numerous different diseases, including MS.

In 2014, Dr. Jeff Cohen of the Cleveland Clinic reported the safety results of an open label trial of mesenchymal stem cells in a group of 24 people with MS. Half had relapsing-remitting MS and half had a progressive form of MS. This safety trial is an important first step since it is possible that the infused mesenchymal stem cells could have actually worsened MS. Fortunately, this was not the case. The procedure was well tolerated and trials will now move forward to look for improvement in disability and functioning with mesenchymal stem cell infusions.

This same institution also shed light on how mesenchymal stem cells might actually promote repair in MS. Using a clever technique in a mouse model of MS, researchers found that a molecule called hepatocyte growth factor may be responsible for the neural repair seen with mesenchymal stem cells. After showing that mesenchymal cells promoted repair in the mouse model of MS, researchers then infused only the liquid that the mesenchymal stem cells had been grown in. Even without the cells, the liquid also promoted repair, suggesting that the cells were secreting something that promoted repair. This something turned out to be HGF. The research group also noted that infusing HGF directly may not be safe in humans as it may have undesirable effects when it affects tissues other than the brain and spinal cord. Hopefully, discoveries like this will move us one step closer to the cure.

Meanwhile, to our north, the MS Society of Canada, along with the MS Scientific Research Foundation announced funding of a study of mesenchymal stem cells in MS, slated to begin in 2015. A $4.2 million grant will fund the MESCAMS study and examine the effects of mesenchymal stem cells in 40 individuals with MS.

Multiple other studies are ongoing globally, including trials at the Tisch MS Research Center of New York, a trial in the United Kingdom and others. While mesenchymal stem cells offer exciting potential, other researchers are working on converting skin cells into myelin-repairing stem cells. These skin cells are easily obtained and have no potential for being rejected as they come from the person’s own body.

Risks and benefits of for-profits

This brings us to our final stem cell topic. While there are currently more than 2,000 trials of stem cells for a variety of health problems globally, there are also numerous for-profit clinics offering stem cell treatments. For the person with aggressive MS, progressive forms of MS or MS not responding to traditional therapies, the attraction of these clinics is obvious. They offer hope. Is this hope realistic, however? A fascinating article titled “Stem cell Tourism – A Web-based Analysis of Clinical Services Available to International Travellers” was published in “Travel Medicine and Infectious Disease” in 2014. The authors noted that the number one treatment indication listed by these clinics was multiple sclerosis. These clinics also offered their treatments for reversing the effects of aging, Parkinson’s disease, stroke, spinal cord injury, Cerebral Palsy, Autism, ALS, Alzheimer’s disease and arthritis. Surprisingly (at least to me) was the fact that the majority of clinics (27 to be exact) were based in the United States. This may be misleading in that some of these clinics are based on the U.S./Mexico border with the actual treatments taking place in Mexico. China, India and Thailand rounded of the global top four for the number of for-profit stem cell clinics.

Any healthcare decision involves an informed discussion of the risks and benefits, along with a discussion of the alternatives to the proposed treatment. The authors of the stated article note that for-profit stem cell clinics are definitely a case of “buyer beware.” The source of the infused stem cells is sometimes unknown. Published treatment results are rare and claims of effectiveness largely based upon anecdotal reports. Average costs for procedures ranged from $5,000 to $50,000 U.S.

Clearly, “stem cell therapy” encompasses a wide range of topics, some of which should be viewed with cautious optimism, others with a degree of skeptical pessimism. Stem cell research does offer the potential to fill some major gaps in our current MS toolbox. Stem cells may offer hope for neural repair, for treating progressive forms of MS and halting MS that is resistant to traditional therapies. Neural repair once seemed the stuff of science fiction, but now seems a realistic goal for people with MS. Here’s looking toward that brighter tomorrow.