Multiple Sclerosis arises when the immune system mistakenly attacks the body's own cells. CD4+ helper T cells target the neurons' outer coating. This insulation-like layer protects nerve fibers. Damaged nerves can't convey electrical impulses to other body regions, impeding communication between the brain, spinal cord, and other organs.
Demyelination appears differently in each individual. MS-related nerve degeneration produces numbness, tingling, tiredness, and decreased eyesight. Steroids and physical therapy help relieve MS flare-ups and relapses, but no cure exists.
CAR T Therapy
One million Americans have this autoimmune illness, multiple sclerosis. Symptoms, including numbness, double vision, and tremor, might cripple the brain and nerves.
Treatments merely fix the issue, not cure it. CAR T treatment may fill in gaps. While the treatment is best recognized for cancer treatments, it has shown promise in treating lupus and rheumatoid arthritis. Researchers are now applying this to MS.
CAR T Cells Target Autoimmunity
New research published in Science Immunology uses CAR T Therapy to treat MS. The treatment uses Chimeric Antigen Receptor T lymphocytes to attack cancerous cells.
Scientists link novel receptors to a patient's excised killer T cells to generate CAR T cells. This combines the detection capability of an antibody with killer T cell machinery.
When reinfused into the body, CAR T cells have a heightened capacity to detect and kill cells carrying a particular biological tag or antigen.
This CAR T design is effective against cancer but not autoimmunity without modifying the chimeric antigen receptor. The CAR T cell must now target self-reactive helper T cells that promote autoimmune illness.
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CAR T Cell Design For Multiple Sclerosis
Researchers generated a chimeric antigen receptor that binds to MS-related mouse helper T cell receptors in this work. The signaling molecules were the same. A protein complex replaced the antigen-detection antibody region.
It uses a major histocompatibility class II (MHC II) molecule with a flexible linker and a peptide. The team could simply adjust the presentation and targeting of this protein complex, demonstrating its adaptability. They engineered the CAR T cells to target MOG, a protein on myelin that pathogenic helper T cells respond to in MS animals.
Success For CAR T Therapy
Researchers looked at this idea in stages. First, they ensured that CAR T cells' basic design could find and target helper T cells in mice. Almost all of the target T cells were killed by CAR T cells without any lymphodepletion.
The medicine only worked partially in animals with an autoimmune disease that looked like MS. CAR T cells were not able to get rid of 2D2 T cells, which in rats cause MS. Damage-causing helper T cells and MOG CAR T cells can't attach well because they don't have enough affinity, which changes the response.
When given early, the medicine made the disease less severe. CAR T cells did not stop disease-causing helper T cells with low affinity but did stop other disease-causing T cells. Researchers changed how CAR T cells were made so that more cells would live. CAR T cells become more sensitive to helper T cells with low or high affinity for MOG.
Researchers found that MS in animals happens in two parts. Based on how people responded to CAR T treatment, scientists found that pathogenic T cells with higher affinity start the illness, while their counterparts with lower affinity keep it going. The best way to use CAR T cells takes disease stages into account.
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Implications
Multiple sclerosis has been hard to treat for a long time, but this CAR T therapy animal model gives us hope for a cure. Researchers were able to make CAR T cells that target low-affinity and high-affinity helper T cells in mice that cause multiple sclerosis.
Based on these findings, CAR T therapy could be used in a planned way to either prevent disease or lessen its symptoms. If CAR T therapy could be used on people, it could be used to stop MS symptoms from getting worse or treat them more completely.