Minocycline Repurposing for Acute Cerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a severe form of stroke; only 20% of patients have a favorable outcome at 1 year and mortality is 40% at 1 month. Despite the critical need, no medication therapy exists for the treatment of this patient population, and the understanding of the pathophysiology underlying ICH remains incomplete. ICH is known to trigger an inflammatory response including activation of microglia, upregulation of matrix metalloproteinases (MMPs), and increase in oxidative species and inflammatory cytokines resulting in blood-brain barrier (BBB) disruption, hematoma expansion, and edema. Current research primarily focuses on the repurposing of agents that target these deleterious mechanisms, and minocycline (MC) has emerged as a promising therapy for neuroprotection after ICH. MC has multiple mechanisms of action including inhibition of microglia activation, MMP-9 inhibition, and iron chelation, and has been shown to be safe in ischemic stroke populations. Further, in small clinical trials of ischemic stroke patients, MC has demonstrated improved functional outcomes. In animal models of ICH, MC has demonstrated the ability to inhibit MMP-9 upregulation, reduce inflammatory activity, and chelate iron, which has translated to reduced edema and improved functional outcomes; however, clinical trials of MC in ICH have yet to be conducted leaving a sizable knowledge gap. An additional attractive aspect of MC is that if it is shown to be safe in both ischemic and hemorrhagic stroke, this would create the opportunity for ultra-early treatment, potentially in the prehospital setting, expanding its potential for neuroprotection.