More Results for the Use of Immune System Reconstruction to Treat Autoimmunity

More evidence is accumulating to show that autoimmune diseases might be effectively treated by destroying the existing population of immune cells and then recreating them: the problem lies in the configuration and memory of those cells. The challenge in this is that, at present, the methods of destruction are harsh, akin to chemotherapy and certainly not something people would want to undergo for any but the most dangerous autoimmune conditions. A priority for the next few years is to find ways to selectively destroy immune cells safely and with few to no side-effects, at which point this type of immune reconstruction would be a very useful treatment for even minor autoimmunities. More pertinently, it would also open the door for the treatment of age-related dysfunction and failure of the immune system, a large component of the frailty of old age. Much of this decline is related to the accumulation of malfunctioning cells, or cells uselessly specialized to persistent pathogens like cytomegalovirus. If the slate could be wiped clean, we might expect there to be considerable improvement in immune response, even given the greater level of damage in cells and tissues characteristic of old age.

New clinical trial results provide evidence that high-dose immunosuppressive therapy followed by transplantation of a person's own blood-forming stem cells can induce sustained remission of relapsing-remitting multiple sclerosis (MS), an autoimmune disease in which the immune system attacks the central nervous system. Five years after receiving the treatment, called high-dose immunosuppressive therapy and autologous hematopoietic cell transplant (HDIT/HCT), 69 percent of trial participants had survived without experiencing progression of disability, relapse of MS symptoms or new brain lesions. Notably, participants did not take any MS medications after receiving HDIT/HCT. Other studies have indicated that currently available MS drugs have lower success rates.

In the HALT-MS trial, researchers tested the safety, efficacy and durability of HDIT/HCT in 24 volunteers aged 26 to 52 years with relapsing-remitting MS who, despite taking clinically available medications, experienced active inflammation, evidenced by frequent severe relapses, and worsened neurological disability. The experimental treatment aims to suppress active disease and prevent further disability by removing disease-causing cells and resetting the immune system. During the procedure, doctors collect a participant's blood-forming stem cells, give the participant high-dose chemotherapy to deplete the immune system, and return the participant's own stem cells to rebuild the immune system. The treatment carries some risks, and many participants experienced the expected side effects of HDIT/HCT, such as infections. Three participants died during the study; none of the deaths were related to the study treatment. Five years after HDIT/HCT, most trial participants remained in remission, and their MS had stabilized. In addition, some participants showed improvements, such as recovery of mobility or other physical capabilities.



What relationship, if any, does this have to the shrinking thymus? And does anyone know what happens to the marrow as it ages?

Posted by: Seth at February 2nd, 2017 3:25 PM

@Seth: Only structural, in the sense that thymic involution and resulting diminished supply of new immune cells is one of the reasons why the immune system has what is effectively a capacity limit. It then runs into problems because too much of that capacity is taken up by broken, malfunctioning, or overspecialized cells as a result of a lifetime of exposure to pathogens. Hitting the reset button is one way to deal with some of that, but it won't do anything to increase the supply of new immune cells. Some sort of thymic rejuvenation and regrowth would be needed there, among other things, such as restoration of youthful stem cell activity and undamaged stem cells.

Posted by: Reason at February 2nd, 2017 7:02 PM

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