Potential therapeutic targets and medications for arteriovenous malformations of the central nervous system

Arteriovenous malformations (AVMs) of the central nervous system are high-flow arteriovenous shunts that lead to considerable risks of hemorrhagic stroke and neurological deficits in young patients. Due to the complex angioarchitecture and their close anatomical relationship with the brain and spinal cord, the management of brain and spinal AVMs is challenging. Conventional invasive treatments, including microsurgery, endovascular embolization, and stereotactic radiosurgery, are associated with considerable risks and unsatisfactory efficacy. In addition, the lack of medications for AVMs represents an unmet clinical need. In recent years, the pathogenesis of AVMs has been progressively explored. The increased understanding of the mechanisms of the formation, progression, and rupture of AVMs has opened up several potential directions for AVM pharmacotherapy. In recent years, some promising drugs targeting angiogenesis, inflammation, vessel wall integrity, and the mitogen-activated protein kinase (MAPK)-extracellular receptor kinase (ERK) signaling pathway have been tested in a series of clinical investigations. In this review, we summarize the potential mechanisms, preliminary efficacy, and side effects of the candidate medications, including bevacizumab, minocycline or doxycycline, thalidomide, and trametinib, in the treatment of brain and spinal AVMs.