MS Speaks
Multiple Sclerosis => MS - RESEARCH AND NEWS => Topic started by: agate on February 28, 2017, 11:33:46 am
-
The keynote address at the recent ACTRIMS conference (February 23-25, Orlando, FL) is abstracted below. Ocrelizumab seems to be the most brightly shining light on the horizon of MS drugs:
Kenneth P. Johnson Memorial Lecture: Multiple
Sclerosis in the Age of B-cell Therapy
Dr. Stephen Hauser – University of California – San Francisco
A significant conceptual change in understanding MS
has been a new appreciation of a role of autoimmune B cells in
mediating tissue damage. In MS, B cells cross the blood-brain
barrier and undergo stimulation, antigen-driven affinity maturation
and clonal expansion within the supportive CNS environment;
activation and expansion of these putative disease-causing
cells also can occur in the peripheral lymphoid system. These
highly restricted populations of clonally expanded B cells and
plasma cells can be detected in MS lesions, in cerebrospinal fluid,
and also in peripheral blood.
Monoclonal antibodies that target circulating CD20-positive B lymphocytes
dramatically reduced disease activity in relapsing forms
of MS, and also were effective, although more modestly so, in the
primary progressive form of the disease. The beneficial effects on
relapsing MS occurred within weeks of treatment, indicating that
a direct effect on B cells—and likely not on autoantibodies—was
responsible. Indeed, the discovery that depletion of B cells has a profound
impact on MS biology enabled a paradigm shift in understanding
how the inflammatory phase of MS develops, and will hopefully
lead to development of increasingly selective therapies against culprit
B cells and related humoral immune system pathways.
The expected launch in early 2017 of ocrelizumab, the first B-cell
therapy to be approved by regulatory agencies, will significantly
alter the MS treatment landscape. However, questions remain
about its proper role. Is a highly effective drug such as ocrelizumab
appropriate as initial therapy for all patients with newly
diagnosed MS? Is lifelong treatment required, or is induction therapy
followed by monitoring and/or maintenance - analogous to a
cancer strategy – adequate? Which patients with progressive MS
should be treated? And finally, what are the advantages of ocrelizumab
relative to other therapies, used off-label or under development,
that also target CD20 or other B-cell surface molecules?