This was on mice, but I thought the findings were interesting nonetheless:
http://arthritis-research.biomedcentral.com/articles/10.1186/s13075-015-0551-3
"Persistent depletion of LLPCs was achieved only by combining a cycle of bortezomib with maintenance therapy, for example cyclophosphamide, depleting the precursors of LLPCs or preventing their differentiation into LLPCs."
Should LLPCs be involved in ME-pathogenesis, and ALSO b-cells; we could be looking at a very complex drug treatment, of a disease where the immune system is severely dysregulated involving a range of different immune cells. This again gets me thinking that side effects will be hard to avoid. Mice behave nice, and dont usually complain to the researchers, but humans do:
http://ard.bmj.com/content/74/7/1474
"Upon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies"
And even:
"Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼50%)"
Although:
"
their numbers increased between cycles."
So this begs the question if e.g. cyclo should used in conjunction with bortezomib, as suggested in the mice-study. However in the latter study:
"
Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients"
From the conclusion:
"The clinical efficacy of bortezomib is remarkable considering that all patients had been refractory to immunosuppression before. Proteasome inhibition may thus serve as a salvage therapy in patients with refractory SLE, in particular as induction therapy in serologically active patients presenting with severe and potential life-threatening organ manifestations. Since most of the clinical effects were achieved within the first 21 days of bortezomib treatment, few cycles of bortezomib induction therapy may be sufficient to ameliorate disease manifestations, and even restore responsiveness to conventional immunosuppression. The observed effects of proteasome inhibition may be partially attributable to the coadministration"
It`s becoming clear that Rituximab only leads to full long lasting remission in a few patients (at least based on phase 2), therefore it is expected that it will be part of a drug cocktail in the future, as relapses indicates that other immune cells are involved. Rituximab together with cyclo and bortezomib; is theoretically intriguing, if the hypophesis is that ME is a variant of an autoimmune disease. But is it
possible?
Did you ever use a third invasive immunosupressive together with rtx and cyclo in RA
@Jonathan Edwards ?
I mean, the amount of severe side effects is likely to increase the more invasive immunosuppressives one include in the drug treatment, and my fear is that it gets to a point where it is less dangerous to undertake an allogeneic stem cell therapy, which one could say is the ultimate immunosupressant?
I guess also one have to accept, that since ME is a serious multi system disease, serious drug cocktails will probably have to be used to get rid of it..
Just some thoughts in the morning, with my first cup of lovely coffee..
Edit: On second read the adverse effects didn`t actually seem too bad, but it might have been of course.
