Targeting complement in neurodegeneration: challenges, risks, and strategies

Evidence implicating complement in neuroinflammatory and neurodegenerative diseases (NDDs) has accumulated over the past decade, revealing complement as a driver of pathology across these diverse diseases. Over the same period, there has been an explosion of interest in the development of complement -modulating drugs, first for a few rare complement dysregulation diseases but recently also for more common diseases where complement contributes to the disease process. To date, there has been little attention paid to the potential role of anticomplement drugs in neurodegeneration and the current landscape does not feature drugs that can enter the central nervous system (CNS), a pre-requisite in most NDDs. Here we summarise the evidence implicating comple-ment in neurodegeneration, build the case for testing anticomplement drugs, and discuss how drugs may be modified or designed de novo to inhibit comple-ment in neurodegeneration.

Automated summary

This article summarizes the role of complement in neurodegenerative diseases and makes a case for testing anti-complement drugs. It also discusses how drugs can be modified or designed to inhibit complement in neurodegeneration.