Drug design for specific inhibition of the Membrane Attack Complex (MAC) in common inflammatory diseases
Many common diseases affecting different parts of the body and with different outcomes are caused by inflammation; examples include rheumatoid arthritis, vasculitis, multiple sclerosis and even dementia. For many of these diseases treatment options are limited; drugs that specifically block inflammation (anti-inflammatory) are widely used and of some benefit, but neither cure the disease nor, in many conditions, prevent worsening. There is a need for better ways of stopping inflammation in these diseases. One novel approach is to target factors that drive inflammation.
Complement is a system of proteins in blood that exists to deal with bacterial infections, a first defence against bacteria that can both:
- directly kill bugs
- provoke white blood cells to eat them
Its importance can be seen in rare patients who lack a complement system; they get repeated, severe infections that can lead to death. As is common in nature, this critical defence system comes at a cost; the system when switched on is a powerful driver of inflammation, essential for its bug-killing roles, but over-activation of the system can drive too much inflammation, resulting in damage to our own cells and tissues and thus to disease. Turning down or switching off complement is therefore a potential way in which disease-causing inflammation could be suppressed.
I am trying to identify better (and potentially cheaper) ways of blocking MAC that might enable treatment of common inflammatory diseases, initially by making immune molecule called monoclonal antibodies (mAb) that bind to and block the MAC. I have already developed a potential mAb. The existing drug Eculizumab is itself a mAb and my new mAb works at least as well in tests of MAC inhibition. However, to use my new mAb as an economic drug therapy, further research is needed. The Fellowship, therefore, will enable me to build on these achievements and hopefully move rapidly in the direction of better, safer, cheaper MAC-blocking drugs for treatment of common inflammatory diseases.