Clinical trials are the way to explore whether cell-based therapies are viable options for treating multiple sclerosis, a group of experts concluded in a publication exploring the state of research in the field.
The article, “Cell-based therapeutic strategies for multiple sclerosis,” was the result of discussions held at the International Conference on Cell-Based Therapy for Multiple Sclerosis in 2015. The experts reviewed evidence on a range of cell therapies, including stem cell transplants and delivery or stimulation of various cell types.
Clinical trials, the panel argued, would be the optimal way to examine which types of cells should be used, how they should be delivered, and the types and disease stages the treatments are suitable for.
The article, published in the journal Brain, focused on four types of cell-based treatments: autologous stem cell transplants, mesenchymal and related stem cell transplants, use of drugs to manipulate stem cells in the body to boost their ability to repair, and transplants of oligodendrocyte progenitor cells to trigger new myelin production. Loss of the myelin that protects neurons is a hallmark of MS.
Such treatments hold promise to attain what current disease-modifying therapies in MS have not: halting the disease without lifelong treatment that has potential side effects, and regenerating damaged tissue.
The International Conference on Cell-Based Therapy for Multiple Sclerosis was sponsored by the National MS Society — which brought attention to the review in a news release — and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Although plenty of research continues, there are issues that need to be resolved in order to steer the research in a healthy direction.
For instance, studies of autologous stem cell transplants have used an array of protocols and approaches. This makes it difficult to compare study results. The expert group said stem cell research would be better performed by networks of scientists who have agreed on a standard protocol.
Researchers also need to determine how to measure whether a stem cell therapy is working and how to monitor patients for safety.
For each approach, it is also necessary to determine which patients are likely to benefit from the treatment — evidence that is currently only available for autologous stem cell transplants.
Risks of procedures outside trials
In addition to reviewing the evidence surrounding cell-based treatments, the expert group focused on the availability of the treatment options outside controlled trials.
“Media attention has resulted in some cases of misrepresentation and exaggeration of therapeutic claims for cell-based therapies for multiple sclerosis and other diseases,” the team wrote.
This has caused patients to seek the treatments — paying out-of-pocket — at unregulated clinics.
“Often such clinics are — for obvious reasons — based in jurisdictions with less stringent medical regulatory structures, and so there can often be little if any assurance of the expertise, quality of care (or even hygiene), or ethical standards of the provider centre, which is often unwilling or unable to seek more traditional financial support for their ‘research,’” they wrote.
Such clinics should at least confirm that the procedure is carried out by staff with appropriate qualifications, training, and experience. The clinic, and the treating physician, should also offer a written treatment plan, which should mention how complications will be monitored and managed, the team argued.
Autologous stem cell transplants
By far the most well-researched cell-based treatment option in MS is autologous stem cell transplants. The treatment, based on isolating a patient’s own blood or bone marrow stem cells, is combined with chemotherapy to wipe out the patient’s currently defective immune system. Once the immune system is eradicated, doctors transplant a patient’s stem cells back into the body to reboot the system.
The new stem cells give rise to a new population of immune cells, which — if the treatment works — do not cause the autoimmune properties characteristic of MS.
While evidence suggests the treatment may be highly efficient in certain patients, it is not clear how it compares with other treatments that are considered highly effective.
The use of chemotherapy to eradicate a patient’s immune system brings with it risk of death. The experts, led by Dr. Neil Scolding of Southmead Hospital Bristol in the United Kingdom, noted that while procedures have become safer in recent years, risk remains the main argument against the treatment.
Patients with MS typically live for decades after a diagnosis, so “any therapy with significant risk of mortality will not readily be accepted,” the team wrote.
To evaluate the risk-efficiency profile of the treatment, a multi-center Phase 3 trial is needed to compare stem cell transplants with approved highly effective drugs.
Evidence is clear about who might benefit from such a treatment, the team wrote. Patients with active relapsing-remitting MS who are relatively young, with a disease duration of less than five years, are good candidates for the procedure, particularly if they do not respond to other treatment, evidence indicates.
In contrast, it is unlikely that autologous stem cell transplants will benefit patients with a long disease history or those who have progressive MS without recent inflammatory activity, they argued.
In an effort to improve the gathering of evidence supporting the treatment, they suggested that physicians who perform transplants outside the scope of clinical trials should collect data on the treatment’s safety and effectiveness and submit it to registries.
In addition, transplants should be performed at centers with MS expertise that are experienced in the procedure, the experts recommended.
Mesenchymal Stem Cells
Researchers have increasingly focused on mesenchymal stem cells’ power to treat various conditions, including MS. These cells are found in several adult tissues, including fat, umbilical cord blood, and bone marrow.
In contrast with the autologous stem cell transplant procedure, the use of mesenchymal stem cells does not involve chemotherapy. The idea is rather that the cell therapy should trigger the body’s own regenerative processes to repair damaged tissue.
To start the procedure, doctors isolate cells from a patient, grow them in a lab in a process that gets rid of other cell types, and inject them back into the patient. The injection can either be intravenous or through a spinal tap to inject cells into the central nervous system.
So far, there have only been small clinical trials of the procedure in MS patients. And researchers have yet to optimize the source or dose of cells that should be used, or the best method to grow and re-inject the cells into patients.
Several larger Phase 2 trials are underway, however, the team noted. These trials may clarify whether the treatment is effective in treating MS, and reveal which patients are likely to benefit.
In the central nervous system, myelin is produced by glial cells called oligodendrocytes. Researchers believe it may be possible to regenerate myelin by transplanting stem cells destined to become oligodendrocytes.
But the expert panel noted that there is evidence suggesting that it is not a lack of such cells that prevents remyelination. Rather, the absence of necessary factors in the body or the presence of inhibitory factors might be at work, they suggested.
Since MS involves damage not only to myelin, but also to nerve cell axons — the long cell projections that send signals outward from a neuron — it is also relevant to find out whether damaged axons can be remyelinated, they argued.
Moreover, researchers are unsure of how to prove that remyelination actually occurs in MS patients exposed to the therapy.
The U.S. Food and Drug Administration recently approved such an approach to be tested in patients.
Boosting regeneration with the help of drugs
Although this approach differs from the others the panel reviewed because it does not involve the handling of cells, it deserves mention.
The panel noted that several drugs in development, including opicinumab, are aimed at promoting remyelination. In addition, drugs that are already approved for other conditions might have remyelinating properties, and might be repurposed to treat MS.
Although studies are ongoing, the panel noted that it is unclear if the drugs do promote remyelination.
Despite ongoing research and — in some cases — clinical use of cell-based therapies for MS, these treatments should be considered experimental, the expert group concluded.
They again underscored the importance of clinical trials in providing a controlled environment for patients wishing to have cell therapy, as well as a source of evidence for the feasibility of these approaches.