The clinical research program described in this report is dedicated to the translation of basic research findings into clinical trials of novel therapies for inflammatory bowel diseases (IBD). In addition, it is structured so as to use basic research methods to define the immune and genetic mechanisms underlying IBD in a variety of settings. This year's research accomplishments include the completion of a protocol studying the safety and efficacy of intravenous infusions of ex vivo cultured adult human mesenchymal stem cells for the induction of remission in subjects experiencing treatment-refractory moderate-to-severe Crohn's disease. This study was performed in conjunction with Osiris Therapeutics, Inc., who oversaw the multi-center trial. In addition to the multi-center trial we also performed a NIH-specific sub-study. Human mesenchymal stem cells (MSCs) reside in bone marrow and are undifferentiated, pluripotential cells that give rise to mesodermal tissue types. These cells can be isolated from BM, cultured, and expanded many-fold. Previously, in both in vitro, animal models, and human clinical studies, MSCs have been shown to home to damaged tissue in the intestines, inhibit immune and inflammatory responses, and repair damaged intestinal tissue.
The aim of the multi-centered study was to assess the clinical response of two infusions of MSCs in patients with active Crohn's disease symptoms.
The aim of our sub-study was to further examine the cytokine and immune cell changes that occur after infusions of study drug, and to correlate these changes with the clinical response of the patient. We were able to screen four patients for the protocol and three patients successfully completed the initial phase of the study. Two out of the three patients had a clinical response to the study drug infusion, with one patient achieving remission of symptoms. The third patient did not achieve a sufficient drop in her Crohn's Disease Activity Index score within the designated time point to qualify as a responder;however, a few weeks after that time point the subject did go into clinical remission. We were able to perform our cytokine/immune cell analysis in all three patients successfully in both the peripheral blood and at the gut mucosal level. In addition, in an extension study the first two patients also received two additional infusions and were studied during that time period as well. The samples/data is still being processed so we are unable to comment on the results at this time. Unfortunately the study was stopped prematurely by the company due to an unusually high placebo response rate, and we no longer have access to the study drug. We will continue to process the samples that we have obtained.
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