Taming an unruly immune system: a risky stem cell transplant that changed fate of some Canadian MS patients

By Hamideh Emrani (@HamidehEmrani)

This year, Dr. Harold Atkins was honored with the Till & McCulloch Award. He and Dr. Mark Freedman led a clinical trial that used stem cells to reset the immune system as a treatment strategy for Multiple Sclerosis (MS) and a few other neurodegenerative diseases, such as stiff person syndrome.

Dr. Harry Atkins
Dr. Harry Atkins; Image credit Signals Blog

You can read how this trial has affected patient Jennifer Molson here.

This trial was a hypothesis-driven interventional clinical trial. The researchers hypothesized that through chemotherapy they could completely obliterate the autoimmune active cells (immune cells that attack a patient’s own body) and, with the help of purified hematopoietic stem cells (HSCs: blood stem cells isolated from the bone marrow), completely reset the immune system so that it would become self-tolerant again. In order to avoid complications from transplant rejection, they would use the patient’s own stem cells.

For this study, they first collected and cryopreserved the patient’s own bone marrow. Then they put the patient through multiple regimens of chemotherapy to eliminate the patient’s immune system. HSCs constitute 3-5% of the bone marrow, and the mixture was thawed and purified (by selection for HSCs) and 48 hours after the last dose of chemotherapy, transplanted into the patient. The patient was then nursed through the period of side effects and the process of immune-reconstitution and monitored to evaluate the MS disease status.

As briefly described in another post I wrote, MS has different stages. During the relapsing remitting stage, an attack by the immune system on the central nervous system, (CNS: brain, optic nerve and spinal cord), results in damage. The CNS has repair mechanisms that go into motion during the remission stage and try to repair the damage. But with each attack, this repair process is slowed down. After multiple attacks, the patient goes into the neurodegenerative phase of the disease, where the body cannot repair the damage anymore.

Before the transplant, many of the patients in the trial had multiple disabilities. After the transplant, 70% of the patients had improved. The 30% that continued with the same disability had already entered the neurodegenerative stage of the disease. However, there was a profound suppression of relapses in all patients.

Relapsing attacks of the immune system appear as lesions detected through positive scans on the MRI machine. While many patients had positive MRI scans before the transplant, there were no new lesions after the transplants. In fact, 70% of the patients have been stable with no relapse activity for over 14 years of follow up.

The purpose of the trial was to stop the progression of disability due to MS. But surprisingly, for 40% of the patients, not only did disability stop but there was also recovery. Even when there was no improvement in mobility, there were improvements in cognitive ability, memory and bowel and bladder function. It seems that once the inflammatory attack of the immune system stops, the brain has the ability to heal.

This trial is not without consequences though. One of the patients died due to toxicity effect of the chemotherapy regimen, which is a common side effect from transplants. But as the researchers have refined the protocol, they have been able to keep the toxicity under control. There were additional side effects such as shingles, thyroid disease and premature menopause and, in one case, secondary leukemia.

Overall, the researchers were able to change the natural history of the disease and, unexpectedly, reduce the burden of disability in a fraction of the patients. As seen in Jennifer’s story, the impact for the patients has been beyond the disability score; some were able to go back to work, back to school, to form relationships, even have children. They are much more independent.

Drs. Atkins and Freedman have used this technique for other autoimmune diseases. They have done a total of 94 transplants at The Ottawa Hospital, half for MS patients. The other half have been patients with myasthenia gravis, stiff person syndrome(SPS), CIPD and NMO. Although some are still at early stages of the trial, 95% of the patients have seen improvements. Last year I shared Tina Ceroni’s story. She underwent the same procedure for stiff person syndrome and has been in remission ever since.

I sat down with Dr. Atkins after he gave the Till & McCulloch Award lecture and asked him a few additional questions.

What criteria determine whether an MS patient would be eligible for the stem cell transplant?

We chose the patients based on their level of disability, measured through a scaling system called the expanded disability status scale (EDSS), the pattern of the disease, ongoing disease activity and progression despite receiving immunomodulatory, and immunosuppressive treatments (medicinal strategies to manage and control the immune system). You can read more about the inclusion criteria in the original publication.
Do you know whether the repair, which was seen in the patients who received the treatment and had significant functional improvements, was also due to the stem cells?

This is not easy to answer, since the whole mechanism is still unknown. What we think might have happened is that taking away the inflammation, caused by the immune system attack, allowed the central nervous system’s intrinsic repair mechanisms to work and the healing to happen. In order to know what exactly happens we will need to be able to generate appropriate imaging data. We are not there yet.

Have you studied effects of female hormones on both the relevance of the disease and the outcome of treatment regimens? Do you know if any group is studying this? I am curious since there is a higher prevalence of MS among females.

The role of female hormones has not been studied. Both male and female seem to respond equally well to this treatment. I cannot comment on other treatments or relevance to the disease.

How can patients be actively involved in their treatments? Other than “going” to the Internet?  

The Internet can be a good source of information if credible sites are used. The trouble is finding the appropriate information by knowledgeable and reputable sources. In addition, patients can rely on their physicians, other MS clinic health care providers and the MS societies to learn about their disease and treatments.

Is this treatment available now, and how can patients enroll?

For the right patient, yes. This treatment is available and we receive a lot of requests to be considered for this treatment at The Ottawa Hospital. However, MS has many different variations among patients and there are many treatment options that are far less risky, with fewer side effects, available these days. (Compared to the start of the trial, 15 years ago.) For each patient the best strategy is to listen to their care team and neurologist to see whether they would benefit from such a treatment.

Make sure to also read a more personal interview with Dr. Harold Atkins here.

Shared with permission from Signals Blog.

About the author: Hamideh Emrani is a scientific communicator and the founder of Emrani Communications, serving clients in Toronto (University of Toronto) and California (Stanford University). She earned her B.Sc. in Cell and Molecular Biology at UC Berkeley and finished her M.Sc. at the University of Toronto (U of T). She was an intern at the Carnegie Institute at Stanford University, honours research student at UC Berkeley and has won awards for best podium and best poster presentations at the Faculty of Dentistry and IBBME at U of T. She is passionate about science and loves to talk and write about it. You can follow Hamideh on Twitter at @HamidehEmrani.

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