#MSResearch #MSBlog Both parts of a potential cure are safe, just need to put them together. The effect without the side effect
The problem with all current MS treatments is that they are not very effective and have side -effects or they are more effective but have more serious side-effects, This is because these treatments remove part of the immune repertoire that is used to fight infections and cancers. The only thing that gives the immune response its specificity is the target recognition receptors on white blood cells. So if you could only target the immune response that is causing the disease and leave the rest of the immune system intact you would have a treatment that works but would have essentially no side effects…….. The Holy grail of Treatments in Immunology.
Lutterotti A, Yousef S, Sputtek A, Stürner KH, Stellmann JP, Breiden P, Reinhardt S, Schulze C, Bester M, Heesen C, Schippling S, Miller SD, Sospedra M, Martin R.Antigen-specific tolerance by autologous myelin Peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013 Jun 5;5(188):188ra75. doi: 10.1126/scitranslmed.3006168.
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 × 10 9 = 1 US billion cells) 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.
This shows you need to give a lot of antigen it may be easier to make biodegradable beads and the peptide mix so you do not have to individualise the approach as the cells are just dead carriers to keep the peptides hanging around..
Much easier than have bone marrow transplants. Will it work well the mechanism states that T cell proliferative responses (reversable with IL2) with be reduced
This concept was borne in the Dr Windy Miller Lab or is that Chicago Steve and is truly a translational approach from mouse to Man so well done to Steve Miller and the Clinical Crew who got this off the ground.
We (Team G) believe that they should deplete the T repertoire before delivering the the intravenous myelin antigens. This should be done when the immune cells are recovering from the depletion and it causes a re-education of the immune cells such that they are no longer self aggressive.
Depletion of immune cells in MS has already been done and this approach is safe so if you put this current approach with the deletion event you can make the two approaches, which may be not optimally effective when used individually and may completely stops relapsing disease when used in combination.
P.S. We may have had our bit to play in this one…..according to our Spies but that’s another story.