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Discovery key to halting nerve fibre damage in MS

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  • Discovery key to halting nerve fibre damage in MS

    A study led by an RMIT University researcher has found blocking a specific protein may be able to act as “hand brake” to the progression of multiple sclerosis (MS).

    The findings have been published in the prestigious journal Brain from Oxford University Press.

    The study was led by Dr Steven Petratos from RMIT’s School of Medical Sciences and the Monash Immunology and Stem Cell Laboratories.

    MS, a chronic neurologic disease that affects up to 20,000 Australians, is thought to be caused by the body’s own immune system mistakenly attacking the brain, spinal cord or optic nerves.

    The primary target of this attack is myelin, the protective coating around the nerve fibres, which carry nerve impulses between nerve cells. These attacks cause active MS lesions and the nerve cells themselves can also be damaged.

    The research team headed by Dr Petratos has shown a modified version of a specific protein is present within active MS lesions in a laboratory model of MS.

    This modified protein interacts with another protein to cause nerve fibre damage but, when the scientists blocked either the modification or the interaction between the two proteins, the progression of the disease was halted.

    Dr Petratos said the particular method used to form the block has already been approved for the treatment of other disease conditions by the US Food and Drug Administration and Australia’s Therapeutic Goods Administration.

    “This should mean that clinical trials – once they start – will be fast tracked, as the form of administration has already been approved,” he said.

    The research was conducted in collaboration with scientists from the University of Toronto and Yale University in the US, with major funding from the National Multiple Sclerosis Society of the United States of America and partial funding from MS Research Australia.

    “This is a great step forward in providing better treatments for MS and hope for people with the disease,” Jeremy Wright, CEO of MS Research Australia, said.

    “We are very pleased to be involved via funding this project.”

    The publication of the discovery comes as Australians are asked to Kiss Goodbye to MS in many events leading up to World MS Day on 30 May.

    MS tends to strike early in adulthood, with women three times more likely than men to be diagnosed.

    About 1,000 new diagnoses of MS are made each year in Australia, with the total cost of the disease to the community estimated at $1 billion annually.
    "I'm manic as hell-
    But I'm goin' strong-
    Left my meds on the sink again-
    My head will be racing by lunchtime"

    <----Scott Weiland---->

  • #2
    Stem Cells for MS

    A study into the use of autologous stem cell treatment for Multiple Sclerosis is currently recruiting patients and hopes to establish the safety and incidence of side-effects for this novel therapy using patients’ own cells to treat their condition. Based at the Royan Institute in Iran, the study’s directors aim to recruit thirty patients, all with the relapsing-remitting form of Multiple Sclerosis (MS). Stem cells will be harvested from the patients’ bone marrow, filtered, and then transplanted by intravenous injection into half of the patients, with the others acting as a control group during the trial. Although this Phase I clinical trial (NCT01377870) is focused on safety, there is anticipation amongst patients of a cure or effective stem cell treatment for MS, especially following the preliminary results published by Connick, et al, in January this year.

    How the MS Stem Cell Trial Works

    The patients in the study will all undergo brain and cervical MRI scans, along with a variety of other medical tests and quality of life questionnaires at one month, three months, six months, and twelve months after the stem cell treatment or placebo. Patients in the placebo group will also have their stem cells extracted but these will be frozen for six months and a sham cell medium without the cells injected instead. The trial design is double-blinded, removing the likelihood of either the participants or the investigators influencing the outcome based on perception. Patients in the control group will be given their stem cell injections six months after extraction with the stem cells frozen and stored during that time.

    What is Multiple Sclerosis – and Why Might Stem Cells Help?

    Multiple sclerosis is a multifocal inflammatory disease of the central nervous system, with a variety of proposed causes and mechanisms. Patients are often affected in their early to mid twenties although first signs of MS can be missed in otherwise healthy individuals. Depending on the type of MS, symptoms may progress slowly over time, may go into remission, or could lead to rapid loss of sensation, motor control, and cognitive deficits. An autoimmune reaction is the most commonly cited explanation for the symptoms of Multiple Sclerosis, with this dysfunction prompting a self-propelled destruction of the insulating myelin around nerve fibers.

    Other theories as to the cause of MS symptoms include bacterial infection (with Lyme disease, for example), iron overload and free-radical damage, and chronic cerebrospinal venous insufficiency (CCSVI), although this has been largely discredited. A genetic predisposition to MS has been uncovered in recent years, which could help researchers target specific components of stem cell behavior in order to promote myelin repair. Once myelin has been stripped from the neurons it is almost always unable to regrow, making the loss of insulation and damage to nerve communication irreparable. The hope is that the regenerative powers of stem cells can prompt recovery of this lost myelin and reverse, or slow, symptom progression.

    Current MS Treatments

    Multiple sclerosis is a condition involving lesions or plaques in the brain itself and/or along the spinal cord. Inflammation around these lesions is thought to be responsible for the periodic symptoms associated with the disease, and some patients’ symptoms abate to some degree once inflammation is brought under control. As degeneration builds however, the disease progression can accelerate, with irreversible axon damage occurring. Immunosuppressant therapies can help reduce the severity of MS attacks, slow down disease progression, and even allow some patients to go into remission in terms of one or more symptoms. No treatment for MS exists however which effectively stops the progression altogether or restores the myelin lost to the disease.

    Bone Marrow Stem Cells for Multiple Sclerosis

    Bone marrow-derived stromal cells can affect the immune system (said to have an immunomodulatory effect) and aid neuroregeneration like neuronal stem cells, at least in the laboratory. This animal research involved the injection of such mesenchymal stem cells into animals with an induced MS-like disease (experimental autoimmune encephalomyelitis). The stem cells appeared to have a neuroprotective effect and their relative ease of availability, in comparison to neural stem cells, makes them an ideal candidate for stem cell therapy for MS. Mesenchymal stem cells are also unlikely to be rejected by the patient in receipt of their own cells, and they are thought to present a lower risk of malignant development upon implantation.

    Expectations for the MS Stem Cell Therapy Trial

    Patients will not only be assessed using diagnostic imagery to monitor lesion development, repair, or stasis, they will also undergo tests for cognitive effects of the treatment. Somewhere between 45% and 60% of patients with Multiple Sclerosis experience cognitive impairment, with memory deficits the most common such symptom. The Rao test is considered a good indicator of the cognitive status of patients with MS and this trial into stem cell therapy for MS will make use of such a test as a measure of secondary outcomes, after safety.

    Eligibility for the MS Stem Cell Trial

    Patients have been recruited for this clinical trial but the recruitment window remains open and the researchers are aiming to complete their active research by August 2012. To be eligible for the trial patients must be between 18-55 years of age, have had MS for two to ten years, and have experienced little benefit, if any, from immunomodulatory and cytotoxic drugs. As the clinical trial is the purview of the Royan Institute in the Islamic Republic of Iran, it is unlikely that US patients with MS will be involved in the research but the findings from the MS stem cell trial could help patients worldwide.


    Connick, P., Kolappan, M., et al, Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study, The Lancet Neurology, Volume 11, Issue 2, Pages 150 – 156, February 2012.

    Royan Institute, Evaluation of Autologous Mesenchymal Stem Cell Transplantation (Effects and Side Effects) in Multiple Sclerosis,
    "I'm manic as hell-
    But I'm goin' strong-
    Left my meds on the sink again-
    My head will be racing by lunchtime"

    <----Scott Weiland---->