Inflammation is the causative common denominator for most of the allergic and autoimmune conditions that plague humans.  Inflammation is mediated at a cellular level by inflammatory proteins.  Many current therapies work by inhibiting the function of inflammatory proteins.  But a new evolving strategy is to develop protein degraders to remove these inflammatory proteins completely. 

Targeted protein degradation is a process using a new class of medicines that may revolutionize the treatment of inflammatory diseases.  These medicines are designed to selectively target and promote the degradation of disease-associated proteins.  By ramping up the body’s natural protein disposal system targeted protein degradation can remove the pathological proteins that are causing cellular inflammation.   

All of our human cells have a garbage disposal system for removing unwanted or senescent proteins.  It is a good system but of limited capacity.  When cells are overwhelmed with a myriad of inflammatory proteins the disposal system simply can’t keep up, think sanitation strike scenario.  The system works in large part by tagging unwanted proteins with a molecule called ubiquitin.  (In my adopted home state of Alabama, we’d pronounce that as “you-be-quitin”  as in “you’re out of here”).   

So, protein degrader medicines work by dramatically enhancing the ubiquitin targeting process, thus speeding removal.  Keep in mind it is only the unwanted proteins that are specifically targeted.  One benefit of this approach over protein inhibitors is the complete removal of the bad proteins, not just inhibiting them.  In the latter case a log-jam can occur where there is such a large buildup of the bad proteins not all of them can be inhibited and hence inflammation continues.  Another benefit of degraders over inhibitors is that inhibitors can also block important cellular processes thereby suppressing desirable immune function (i.e. they can suppress the immune system leading to a greater chance for infections).   

Early research trials with a degrader IRAK4 have shown it to be effective in treating two skin diseases:  atopic dermatitis and hidradenitis suppurativa (a chronic condition of boils/cysts in the armpits).  As in all new research there is a lot more study to be done, but the outlook is very promising.