Graft-versus-host disease future or investigational therapies

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Graft-versus-host disease

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Overview

There are a few new investigational efforts in place for GvHD prevention, diagnostics, and therapeutics. These include Aurora kinase inhibitors, capsule endoscopy, and ibrutinib.

Future or Investigational Therapies

  • Regarding prevention, studies have shown that []Aurora kinase]] may be a targetable pathway to prevent GvHD.[1] Transcriptome analysis of CD3-positive T cells from primates during acute GvHD has led to the discovery that Aurora kinase is a druggable target. Aurora kinase inhibitors are available and may be applied to GvHD if future data continues to be promising.[1] Additional preventive strategies include optimization of the graft-versus-tumor and GvHD balance in favor of a graft-versus-tumor effect. This balance might be achieved by manipulating regulatory T cells or NKT cells.[2]
  • Regarding diagnostics, early and more sensitive diagnostic strategies are being studied. Wireless capsule endoscopy has been proposed for upper GI GvHD diagnosis.[3] A pilot study of 15 patients showed that wireless capsule endoscopy could be a novel method for early GI GvHD diagnosis. The benefits are that this procedure is less invasive that a traditional endoscopy and bypasses the potential problem of false negatives, given patchy distribution of inflammation in GI GvHD.[3]
  • Regarding therapeutics, there are a few medications that are currently being investigated for GvHD treatment. Such examples include ibrutinib (a Bruton's tyrosine kinase inhibitor) and ruxolitinib (a JAK2 inhibitor). These medications are not formally FDA-approved thus far, but they may become approved in the near future pending further clinical studies.

There are a large number of clinical trials either ongoing or recently completed in the investigation of graft-versus-host disease treatment and prevention[4].

References

  1. 1.0 1.1 Furlan SN, Watkins B, Tkachev V, Flynn R, Cooley S, Ramakrishnan S; et al. (2015). "Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention". Sci Transl Med. 7 (315): 315ra191. doi:10.1126/scitranslmed.aad3231. PMC 4876606. PMID 26606970.
  2. Patel SA, Rameshwar P (2011). "Stem Cell Transplantation for Hematological Malignancies: Prospects for Personalized Medicine and Co-therapy with Mesenchymal Stem Cells". Curr Pharmacogenomics Person Med. 9 (3): 229–239. doi:10.2174/187569211796957548. PMC 3164538. PMID 21892378.
  3. 3.0 3.1 Coron E, Laurent V, Malard F, Le Rhun M, Chevallier P, Guillaume T; et al. (2014). "Early detection of acute graft-versus-host disease by wireless capsule endoscopy and probe-based confocal laser endomicroscopy: results of a pilot study". United European Gastroenterol J. 2 (3): 206–15. doi:10.1177/2050640614529283. PMC 4212456. PMID 25360304.
  4. http://www.clinicaltrial.gov/ct2/results?term=Graft-versus-host+disease search of clinicaltrials.gov for Graft-versus-host disease]

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