20/20 Research Study

It is difficult to develop effective treatments for a disease when its cause remains unknown.

If Mast Cell Activation Syndrome (MCAS) could be proven to be usually a result of mutations in mast cells, then it probably would be easier (compared to if there were no mast cell mutations underlying MCAS) to learn what makes the different variants of the disease tick and to develop effective (mutation-targeting) treatments. A research team at the University of Bonn (led by senior mast cell disease researcher Gerhard Molderings, M.D.) has found that most MCAS patients bear one or more of a large assortment of mutations in the dominant mast cell regulatory gene KIT (though only rarely is this the one particular KIT mutation (“KIT-D816V”) commonly found in the rare mast cell disease called mastocytosis). However, because no other research team has yet tested MCAS patients for mast cell mutations (whether in KIT or any other mast cell regulatory gene), it remains an open question whether most patients with MCAS really do have mast cell mutations (as suggested by the Bonn data) or whether the (repeated) findings in Bonn are somehow the result of (repeated) experimental error. One of the hallmarks of scientific truth is reproducibility of experimental results by different teams.

Dr. Afrin’s present “20/20” study is studying 20 MCAS patients and 20 demographically matched healthy control subjects looking principally to (1) confirm the published findings in KIT by the team in Bonn (Dr. Molderings and his associates) and (2) extend this work to include roughly 30 other mast cell regulatory genes as well (i.e., looking for mutations present in MCAS patients but not in healthy control subjects). Why other mast cell regulatory genes? Data is emerging from other research teams to support the notion that it’s not just KIT but many other mast cell regulatory genes, too, which are mutated in virtually every patient with mastocytosis, suggesting we ought to find the same in MCAS — if we look. 20/20 is looking for this.

Additional funding is also being sought to extend the 20/20 study to (1) identify whether any mutations found are present in *both* the DNA *and* the RNA of the mast cells and (2) whether the mutations found in the mast cells (comprising a very tiny portion of the body’s white blood cells) are also detectable in the general mass of white blood cells in the body. These findings will have significant implications for developing future, easier testing for MCAS in the clinical laboratory.

Contributions to the Summerall & Klein Mast Cell Disease Research Fund (managed at no cost by the University of Minnesota Foundation) will help support the 20/20 study and other mast cell disease research and education at the University of Minnesota. See donation information below. IMG_8219

20/20 research study and Donation inquiries should be directed to Foundation officer Russell Betts at rbetts@umn.edu or (612) 626-4569.