Following Up on a Trial of an Immune System Reset to Treat Multiple Sclerosis

Some autoimmune diseases can be successfully treated by suppressing or destroying the existing immune system and then transplanting new stem cell populations responsible for generating immune cells. This can result in an effective resetting of the immune system, or at least removal of those parts of it that have become misconfigured to attack the patient's own tissues. It is, however, a pretty drastic process and certainly not one to be undertaken lightly: the sort of chemotherapy required is not a walk in the part for the patient. For autoimmune conditions where even partially effective alternative treatments exist, as is the case for rheumatoid arthritis, for example, researchers have all but abandoned work on the destroy-and-rebuild approach despite some early promising results. Nonetheless, it has been shown to produce results in terms of halting the progression of multiple sclerosis (MS), one of the more serious forms of autoimmunity in which the myelin sheathing of nerves is attacked:

Multiple sclerosis (MS) is a degenerative disease and most patients who receive disease-modifying therapies experience recurrence of the disease process. Three years after a small number of patients with MS were treated with high-dose immunosuppressive therapy (HDIT) and then transplanted with their own hematopoietic stem cells, most of the patients sustained remission of active relapsing-remitting MS (RRMS) and had improvements in neurological function.

Study results indicate that of the 24 patients who received HDIT/HCT, the overall rate of event-free survival was 78.4 percent at three years, which was defined as survival without death or disease from a loss of neurologic function, clinical relapse or new lesions observed on imaging. Progression-free survival and clinical relapse-free survival were 90.9 percent and 86.3 percent, respectively, at three years. The authors note that adverse events were consistent with the expected toxic effect of HDIT/HCT and that no acute treatment-related neurologic adverse events were seen. Improvements in neurologic disability, quality-of-life and functional scores also were noted.

"In the present study, HDIT/HCT induced remission of MS disease activity up to three years in most participants. It may therefore represent a potential therapeutic option for patients with MS in whom conventional immunotherapy fails, as well as for other severe immune-mediated diseases of the central nervous system. Most early toxic effects were hematologic and gastrointestinal and were expected and reversible. Longer follow-up is needed to determine the durability of the response."



What I think they should be doing is filtering the blood and filtering out just the white blood cells that respond to that antigen. I'm sure we have the technology to do that now.

Posted by: Carl at December 30th, 2014 9:37 AM

Yep Carl is right in wondering why we can't just ablate the 'misconfigured' immune cells rather than destroying the entire immune system. They've even got specific B cell and T cell receptors to the self antigens that could be targeted. Now that he has pointed this out I can't think why no one is working on this? Maybe there are some roadblocks that we haven't heard of?

Posted by: Jim at December 30th, 2014 10:26 AM

OK I see scientists are still not 100% sure that a proper immune system reset has taken place. They'll probably need more time on this study, or future follow up studies, before looking at alternate ways to ablate the immune cells. It is kind of frustrating as there are already CAR T cells in clinical trials against CD19 which is expressed on all B Cells. Don't memory T Cells have some common receptor that could be used to produce a CAR T cell against them, ablating the immune system without the risk of death and cancer posed by chemotherapy? As MS kills people you'd think that pharma/biotechs would be interested in this on the "if it bleeds it leads" principal. People with MS would pay anything for an effective treatment just like cancer patients do.

""Nash et al show evidence of prolonged depletion of memory CD4+ cells, depletion of CD4+-dominant T-cell receptor clones and evidence of 'immune reset'; however, clinical or radiologic evidence of relapse trumps immunologic evidence of immune reset, and this study raises concern that those end points have not been adequately achieved. The jury is still out regarding the appropriateness and indication of HCT for MS," the authors conclude."

Posted by: Jim at April 11th, 2015 11:38 AM
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