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Stem cell transplant ‘game changer’ for MS patients

Stem cells and multiple sclerosis

Stem cells and multiple sclerosis

Doctors say a stem cell transplant could be a “game changer” for many patients with multiple sclerosis.

Results from an international trial show that it was able to stop the disease and improve symptoms.

It involves wiping out a patient’s immune system using cancer drugs and then rebooting it with a stem cell transplant.

Louise Willetts, 36, from Rotherham, is now symptom-free and told me: “It feels like a miracle.”

A total of 100,000 people in the UK have MS, which attacks nerves in the brain and spinal cord.

Just over 100 patients took part in the trial, in hospitals in Chicago, Sheffield, Uppsala in Sweden and Sao Paolo in Brazil.

They all had relapsing remitting MS – where attacks or relapses are followed by periods of remission.

The interim results were released at the annual meeting of the European Society for Bone and Marrow Transplantation in Lisbon.

Read the full article here.

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Stem Cell Treatment Benefits Three-fourths of MS Patients in Phase 1 Trial

Stem cells and multiple sclerosis

Stem cells and multiple sclerosis

A stem cell treatment improved the neurological symptoms of three-fourths of the multiple sclerosis patients in a Phase 1 clinical trial, New York researchers reported.

The results prompted the team at the Tisch MS Research Center of New York to start a Phase 2 trial to further assess the therapy’s safety and effectiveness.

Injecting mesenchymal stem cell-derived nerve cell progenitors directly into the spinal canal also improved the muscle strength and bladder function of many of the 20 progressive MS patients.

The study, “Phase I Trial of Intrathecal Mesenchymal Stem Cell-Derived Neural Progenitors in Progressive Multiple Sclerosis,” was published in the journal EBioMedicine.

Eighty percent, or 16, of the patients in the open-label trial (NCT01933802) had secondary progressive MS.

Half were unable to walk at the beginning of the study, and had EDSS disability scores of 7 or higher. Eight required assistance to walk, and had EDSS scores of 6 to 6.5. Two were able to walk without assistance, with EDSS scores between 3.5 and 5.5. EDSS stands for Expanded Disability Status Scale.

Read the rest of the article here.

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Large Study Showed Long-Term Benefits of Bone Marrow-Derived Stem Cell Transplantation in Some People with Multiple Sclerosis

Stem cells and multiple sclerosis

Stem cells and multiple sclerosis

An international study evaluated long-term outcomes from bone marrow-derived stem cell transplantation (autologous hematopoietic stem cell transplantation – HSCT) in 261 people with different forms of MS.

The transplants took place between 1995 and 2006, with a follow-up period of up to 16 years. Several different transplant protocols were followed.

Results suggest that after 5 years, 46% still had not experienced any progression or worsening of symptoms, including 73% of those with relapsing MS and 33% of those with secondary progressive MS. Eight deaths (2.8%) occurred within 100 days of the transplant. Most of these occurred during the early development of the procedure; improvements in patient selection and transplant techniques have significantly reduced the mortality.

Those with the best outcomes tended to be younger, had relapsing MS, lower accumulation of disability and had used fewer MS therapies prior to the transplant procedure.

Additional research is needed to better understand who might benefit from this procedure and how it compares to the benefits of powerful immune-modulating therapies now available.

The study, by Dr. Paulo Murano and colleagues, was published online February 20, 2017 in JAMA Neurology.

Background: HSCT (Hematopoietic Stem Cell Transplantation) attempts to “reboot” the immune system, which is involved in damaging the brain and spinal cord in MS. In HSCT for MS, hematopoietic (blood cell-producing) stem cells, which are derived from a person’s own (scientifically referred to as autologous”) bone marrow, are collected and stored, prior to depleting much of the immune system using chemotherapy drugs. Then the stored hematopoietic stem cells are reintroduced to the body. The new stem cells migrate to the bone marrow and over time reconstitute the immune system.

This Study: Researchers from 25 centers in 13 countries collaborated to evaluate the long-term outcomes from bone marrow stem cell transplantation (autologous hematopoietic stem cell transplantation – HSCT) in 261 people with different forms of MS. The researchers were part of the Multiple Sclerosis-Autologous Hematopoietic Stem Cell Transplantation Long-term Outcomes Study Group. The transplants took place between 1995 and 2006, with a follow-up period of up to 16 years. Several different transplant protocols were followed.

Characteristics of the participants varied widely in terms of age, amount of disability (as measured by the EDSS scale), and type of MS. Most had tried two or more MS therapies. More than 75% of the participants had progressive forms of MS at the time of the transplant, mostly secondary progressive MS but some with primary progressive MS.

Results: Results suggest that after 5 years, 46% still had not experienced any progression or worsening of symptoms, including 73% of those with relapsing MS and 33% of those with secondary progressive MS. Eight deaths (2.8%) occurred within 100 days of the transplant; most of these occurred in transplants made before 2000. Improvements in patient selection and transplant techniques seemed to have lowered the risk for mortality in subsequent years.

The investigators reported that those with better outcomes tended to be younger, had relapsing MS, less disability at the time of the transplant, and had used fewer MS disease-modifying therapies prior to the transplant procedure. By contrast, those who tended to experience MS progression after transplantation tended to be older, had progressive MS, and had tried more than two disease-modifying therapies prior to having the transplant.

Researcher Paolo A. Muraro, MD, PhD (Imperial College London) and colleagues published their results in JAMA Neurolology, published online on February 20, 2017.

This study was co-funded by many agencies including the UK Multiple Sclerosis Society.

“This is one of the larger studies to date that observed long-term outcomes of HSCT in MS,” says Bruce Bebo, PhD, the National MS Society’s Executive Vice President, Research. “Well-controlled trials are needed to better understand who might benefit from this procedure and how it compares to the benefits of the FDA-approved disease-modifying treatments that are now available.” A phase 3 trial of HSCT is now in planning stages. The Society is engaged with the team planning the trial and is encouraging quick action to design and launch the trial.

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Risky stem cell treatment ‘halts progress of multiple sclerosis’

Risky stem cell treatment 'halts progress of multiple sclerosis'

Risky stem cell treatment ‘halts progress of multiple sclerosis’

 

“New treatment can ‘halt’ multiple sclerosis, says study,” BBC News reports.

The treatment involves effectively destroying the existing immune system and creating a new one using stem cells. But this new treatment carries a high risk of complications.

Multiple sclerosis (MS) is a life-long condition that affects the brain and spinal cord, causing a wide range of symptoms, including problems with arm or leg movement, vision, sensation and balance, and serious disability.

It is an autoimmune disease where the immune system mistakenly attacks healthy cells in the body – in this case, the coating of the nerves (myelin sheath).

In this Canadian study, researchers essentiality destroyed a patient’s existing immune system with a very aggressive course of chemotherapy drugs.

They then transplanted stem cells – which have the potential to become any type of blood cell – in an attempt to rebuild an immune system without the flaws that trigger MS.

Of the 24 patients that took part in the study, 70% had no disease activity three years after the transplant, and about a third had sustained improvement in disability status. For example, 16 patients were able to go back to work or college.

One fact to bear in mind, however, is that this was a small study with no comparison group, and one of the 24 patients died after transplant as the result of an infection.

This represents a mortality rate of 4%. Whether or not this was just an unfortunate one-off is unclear.

The risks and benefits of this approach need to be carefully weighed and compared before it can be widely adopted in clinical practice.

Where did the story come from?

The study was carried out by researchers mostly from medical institutions in Canada, as well as three researchers from the Department of Neurosciences, Cleveland, in the US.

It was funded by grants from the Multiple Sclerosis Scientific Research Foundation. Some of the researchers also received personal fees and grants from a number of pharmaceutical and biotech companies.

The study was published in the peer-reviewed journal, The Lancet.

While the UK media was along the right lines reporting news of a ‘breakthrough treatment’, it is slightly premature considering this is a very small, early stage, study.

The media did, however, go on to highlight that further investigation was needed before this treatment becomes available in clinical practice.

It was also correctly reported that this treatment wouldn’t be suitable for many people with less debilitating MS because of the risks it carries.

What kind of research was this?

This phase II trial aimed to assess a new treatment approach of aggressive chemotherapy followed by haemopoietic stem cell transplant (HSCT).

The researchers wanted to see whether this had an impact on clinical relapse and improvements in disability in people with multiple sclerosis.

Haemopoietic stem cells are very early-stage blood cells that can develop into all other types of blood and immune cells.

This study involved autologous HSCT, where stem cells are first harvested from the patient before high-dose chemotherapy is given to deplete the person’s own cells.

The harvested cells were then transplanted in the hope this would allow the immune system to be rebuilt without the flaws that trigger MS.

This is an early-stage clinical trial involving a relatively small number of people and no comparison group. It aimed to see whether the treatment is safe and could potentially be effective.

This is important early-stage research designed to see whether the findings are promising, and may pave the way for further investigation in later trials involving more people and comparisons with other treatments or placebo.

What did the research involve?

The study began in the year 2000, when researchers recruited 24 patients between the ages of 18 and 50 from three hospitals in Canada.

Their disease was defined as having a high probability of significant progression over the next 10 years, having suffered multiple relapses prior to being enrolled in the study.

The patients first had their haemopoietic stem cells harvested, and their immune system was then fully suppressed with aggressive chemotherapy. They then received HSCT two days after their final dose of chemotherapy.

The main outcome of interest was the proportion of patients who were surviving and free from MS disease activity three years after transplant.

This was assessed by looking at clinical relapse, appearance of new MS lesions on MRI scans, and sustained improvements in disability status.

Of the 24 patients, 21 were followed up to three years, and 13 took part in longer-term follow-up. The average follow-up duration was 6.7 years (range 3.9-12.7).

What were the basic results?

Overall, 17 of the 24 patients (69.9%) achieved activity-free survival three years after transplantation. The remaining seven patients had sustained progression of disability.

Clinical relapses did not occur in any of the 23 surviving patients during follow-up. These results were mirrored by no new lesions being seen on 314 sequential MRI scans overall. And 35% of patients had sustained improvements in their disability status.

One patient died of transplantation-related complications, however. There were also various side effects associated with treatment.

Most patients experienced toxicity effects of varying degrees of severity, and fever and infections were common.

How did the researchers interpret the results?

The researchers concluded: “We describe the first treatment to fully halt all detectable CNS [central nervous system] inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs.

“Furthermore, many of the patients had substantial recovery of neurological function despite their disease’s aggressive nature.”

Conclusion

This early-stage trial aimed to look at a new treatment approach for MS, involving aggressive chemotherapy followed by haematopoietic stem cell transplant (HSCT). Researchers then assessed whether this had an impact on clinical relapse and disability.

The study suggests that eliminating an individual’s existing “faulty” immune system, and rebuilding it using stem cells, may slow down or completely halt the progression of MS, resulting in an improvement in disability status.

Although the study’s findings suggest this could be a potential treatment in the future, the researchers say caution is necessary before it is widely adopted in clinical practice.

This was very early-stage research, with a small sample size and no control group for comparison with those who were treated.

The findings were positive overall, but the retention to longer-term follow-up was quite low, with only around half being followed up beyond three years.

This means although there were no documented relapses and around a third improved functional ability during follow-up, these results could be different with a much larger sample size.

Also, the fact there was one death among the 24 treated patients and toxic side effects were common cannot go unnoticed.

Dr Payam Rezaie, a reader in neuropathology at The Open University, commented: “While this study does add considerable weight to the use of autologous HSCT as a therapeutic approach for MS, it is difficult to make a more generalised inference on its use, based on this study alone.

“The risks need to be carefully weighed when compared with the beneficial outcomes. The present study indicates a need to examine this further.”

Further trials in larger groups of people with MS, including those with different disease characteristics, and comparing it with other treatments, would be needed to better gauge the effectiveness and safety of this approach.

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Stem cells ‘reverse’ Multiple Sclerosis?

Stem cells and multiple sclerosis

Stem cells and multiple sclerosis

“Stem cell transplants could provide a cure for multiple sclerosis”, The Sun reported. It said that in a recent trial of 21 patients with MS, 17 had shown improvement three years after being injected with cells from their own bone marrow. The newspaper said the stem cells appear to reduce the inflammation that can worsen the disease. The study leader was quoted as saying: “It seems to prevent neurological progression and reverse disability.”

The news story is based on an early phase trial, which found that stem cell transplants reversed neurological deficits in people with relapsing-remitting MS, the most common form of the disease. It did not look at other forms of the condition, such as secondary progressive MS. Patients were compared before and after the transplant, and the results were promising, with sustained improvements in disability in 81% of patients.

As is usual when testing treatments, the intervention will go on to be tested in larger, controlled trials, probably randomised controlled trials across different centres. Until then, the researchers emphasize that it’s not possible to determine whether this treatment is better than existing treatments for relapsing-remitting MS.

Where did the story come from?

The research was carried out by Dr Richard K. Burt and colleagues from the Northwestern University Feinberg School of Medicine and Department of Neurological Sciences, Rush University Medical Centre in Chicago, Imperial College London, the University of Utah and other international academic and medical institutions. The study was published in the (peer-reviewed) medical journal: the Lancet.

What kind of scientific study was this?

The researchers say that when most people are first diagnosed with MS, they have only intermittent symptoms; a form of the disease called relapsing-remitting MS. Although many go on to develop irreversible progressive MS, which results in gradual reduction in neurological function, MS may be at least partially reversible while in this initial phase.

During its early stages, the immune system limits the damage that MS has on nerve cells. Treatments at this time include immune therapies aimed at improving this response. This early phase I/II study investigated if the transplantation of certain blood stem cells during the relapsing-remitting phase of MS could reverse neurological disability. The process of transplanting blood stem cells back into bone marrow is known as haemopoietic stem cell transplation.

The study involved 21 MS patients aged between 18 and 55 years who had not responded to at least six months of therapy with interferon alpha (an immune therapy). All patients had a minimal to severe disability (according to a well-known disability scale) and had normal lung, kidney, heart and liver function and no history of cancer (except skin cancer).

Before their stem cell transplantations, the patients’ immune systems were prepared for the donor cells by a non-myeloablative pre-treatment. This means that their body’s ability to make blood cells was only weakened rather than destroyed. The patients’ physical and neurological abilities were tested by several assessments including a timed 25ft walk and a nine-hole peg test. These were repeated six and 12 months after the transplantation, and annually after that. The patients were also asked to report any new symptoms or worsening between visits, at which point they would be immediately reassessed.

Disability and function was assessed using the expanded disability status scale (EDSS), the neurological rating scale (NRS) and the paced auditory serial addition test (PASAT). Blood transfusions and antifungal and antiviral treatment were given as necessary during the procedure, and adverse events were dealt with.

The patients were followed up for an average of 37 months and their neurological functioning, progression free survival (the length of time that symptoms do not worsen) and performance on different tests were compared with measures taken before treatment.

What were the results of the study?

The study found that the patients’ average score on the EDSS had significantly improved by 0.8 points six months after the stem cells were transplanted, and had improved by 1.7 points by the fourth year of follow-up. Other measures of neurological function also significantly improved after the transplant for the majority of patients, including assessments on the NRS, the timed 25ft walk and the PASAT. Although there was an improvement in scores on the nine-hole peg tests, these were not significantly different between the time before and after transplantation. The patients also reported that their general health status improved.

Despite showing early neurological improvements, five patients relapsed an average of 11 months after transplantation.

What interpretations did the researchers draw from these results?

The researchers conclude that 81% of patients showed a reversal of neurological disability. They also had sustained improvements in function as demonstrated by improvements of one point or more in EDSS scores. They say that stem cell transplantation reverses neurological deficits in people with relapsing-remitting MS, but caution that these results need to be confirmed in a randomised trial.

What does the NHS Knowledge Service make of this study?

This study focuses on relapsing-remitting MS, which is the most common of the four types of multiple sclerosis. Many people with this type go on to develop secondary progressive MS (a steady worsening in symptoms and disability). It is important to highlight that the findings only apply to people who have relapsing-remitting MS. The researchers state that studies have found no improvement in neurological disability with transplantation in secondary progressive MS.

When new treatments are being tested, they usually go through a three-stage study process before being licensed for use. Early studies – phase I and II trials such as this one – are smaller and often do not have a comparison group with which to compare an intervention. If efficacy (the power to produce an effect) and safety are demonstrated in such studies, the intervention is then assessed in larger studies; the largest being phase III trials which are randomised, controlled studies which can have thousands of patients. Given the promising results in this preliminary study, stem cell transplantation for relapsing-remitting MS patients will probably be studied further in larger trials.

The researchers draw attention to the fact that this study does not compare stem cell treatment with current management of relapsing-remitting MS. Only a randomised controlled trial will provide this answer.