AAV gene therapy reduces cell death following cerebral hemorrhagePublished: July 24, 2019
Researchers have demonstrated the efficiency of AAV-mediated CHIP, an E3 ubiquitin ligase, delivery in inhibiting cell death caused by intracerebral haemorrhage.
Intracerebral hemorrhage (ICH) is the second largest type of stroke and it accounts for around 15% of all patients with stroke. Primary brain injury after ICH is due to hematoma mass effect and mechanical damage to adjacent brain tissues, and the secondary brain injury is a key reason to cause nerve function damage in patients with ICH. Cell death is an important factor in secondary brain injury after ICH.
The E3 ligase CHIP has been previously shown to mediate cell death in ICH. However, there is currently no evidence supporting a function of CHIP in ICH.
In the study published in Translational Stroke Research, Dr Yuming Xu and team at China’s Zhengzhou University tested the role of CHIP in brain injury after ICH.
The study showed that CHIP expression was increased in the peri-hematomal area in rat models of ICH. Administering an AAV vector which carries the gene coding for CHIP reduced brain injury and neuronal cell death in rats after ICH.
To confirm the role of CHIP, the team tested rats with CHIP deficiency and saw that these rats experienced severe brain injury and increased levels of neuronal cell death and inflammation compared to control animals. The effect was fully reversed after treating with AAV gene therapy.
Together, the results highlight the role of CHIP in inducing pathological inflammation following ICH. CHIP overexpression by AAV gene therapy presents a novel avenue for the treatment of brain injury.
Source: AAV/BBB-Mediated Gene Transfer of CHIP Attenuates Brain Injury Following Experimental Intracerebral Hemorrhage. Zhang S et al., Translational Stroke Research, July 2019. DOI