6 June 2013 Last updated at 06:18 GMT
Immune training MS trial 'safe'
By James Gallagher
Health and science reporter, BBC News
An experimental treatment to stop the body attacking its own nervous system in patients with multiple sclerosis (MS) appears safe in trials.
The sheath around nerves cells, made of myelin, is destroyed in MS, leaving the nerves struggling to pass on messages.
A study on nine patients, reported in Science Translational Medicine, tried to train the immune system to cease its assault on myelin.
The MS Society said the idea had "exciting potential".
As nerves lose their ability to talk to each other, the disease results in problems moving and balancing and can affect vision.
There are drugs that can reduce number and severity of attacks, but there is no cure.
The disease is caused by the body's immune system thinking that myelin is a foreign body like a flu virus.
Researchers at the Northwestern University Feinberg School of Medicine developed a technique to retrain the immune system.
They took blood samples and coupled white blood cells, a part of the immune system, to fragments of myelin. This was injected back into the patients to make them tolerate myelin.
The researchers said the therapy appeared safe. The study was too small to prove whether it benefited patients, but the researchers did report a calming of the immune reaction.
Prof Stephen Miller said: "Our approach leaves the function of the normal immune system intact. That's the holy grail."
He said future trials would target patients in the early stages.
He said: "We want to treat patients as early as possible in the disease before they have paralysis due to myelin damage, once the myelin is destroyed, it's hard to repair that."
Dr Susan Kohlhaas, head of biomedical research at the MS Society, said: "Being able to specifically stop the immune system attacking myelin but still keeping it fully functional poses an exciting potential therapy for people with MS.
"We were interested to see this novel way of re-programming the immune system shown to be well tolerated in this very small study.
"More research is now needed and we eagerly await the results of any future larger clinical trials of this therapy."
Sci Transl Med 5 June 2013:
Vol. 5, Issue 188, p. 188ra75
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006168
Antigen-Specific Tolerance by Autologous Myelin Peptide?Coupled Cells: A Phase 1 Trial in Multiple Sclerosis
Andreas Lutterotti1,2, Sara Yousef1, Andreas Sputtek3, Klarissa H. Sturner1, Jan-Patrick Stellmann1, Petra Breiden1, Stefanie Reinhardt1, Christian Schulze4, Maxim Bester5, Christoph Heesen1, Sven Schippling1,6, Stephen D. Miller7,*, Mireia Sospedra1,6,* and Roland Martin1,6,*,†
+ Author Affiliations
1Institute for Neuroimmunology and Clinical MS Research, Center for Molecular Neurobiology, 20251 Hamburg, Germany.
2Clinical Department of Neurology, Innsbruck Medical University, 6020 Innsbruck, Austria.
3Institute of Transfusion Medicine, Center for Diagnostics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
4Systems Biology and Protein-Protein Interaction, Center for Molecular Neurobiology, 20251 Hamburg, Germany.
5Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
6Neuroimmunology and MS Research, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland.
7Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
+ Author Notes
?* These authors contributed equally to this work.
?†Corresponding author. E-mail: email@example.com
Multiple sclerosis (MS) is a devastating inflammatory disease of the brain and spinal cord that is thought to result from an autoimmune attack directed against antigens in the central nervous system. The aim of this first-in-man trial was to assess the feasibility, safety, and tolerability of a tolerization regimen in MS patients that uses a single infusion of autologous peripheral blood mononuclear cells chemically coupled with seven myelin peptides (MOG1?20, MOG35?55, MBP13?32, MBP83?99, MBP111?129, MBP146?170, and PLP139?154). An open-label, single-center, dose-escalation study was performed in seven relapsing-remitting and two secondary progressive MS patients who were off-treatment for standard therapies. All patients had to show T cell reactivity against at least one of the myelin peptides used in the trial. Neurological, magnetic resonance imaging, laboratory, and immunological examinations were performed to assess the safety, tolerability, and in vivo mechanisms of action of this regimen. Administration of antigen-coupled cells was feasible, had a favorable safety profile, and was well tolerated in MS patients. Patients receiving the higher doses (>1 × 109) of peptide-coupled cells had a decrease in antigen-specific T cell responses after peptide-coupled cell therapy. In summary, this first-in-man clinical trial of autologous peptide-coupled cells in MS patients establishes the feasibility and indicates good tolerability and safety of this therapeutic approach.
Copyright c 2013, American Association for the Advancement of Science
Citation: A. Lutterotti, S. Yousef, A. Sputtek, K. H. Sturner, J.-P. Stellmann, P. Breiden, S. Reinhardt, C. Schulze, M. Bester, C. Heesen, S. Schippling, S. D. Miller, M. Sospedra, R. Martin, Antigen-Specific Tolerance by Autologous Myelin Peptide?Coupled Cells: A Phase 1 Trial in Multiple Sclerosis. Sci. Transl. Med. 5, 188ra75 (2013).
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