Antisense oligonucleotide treatment to ameliorate neuroinflammation and cognitive decline after cranial radiotherapy in the juvenile mouse brain
Approximately 100 children annually develop a brain tumour in Sweden. Radiotherapy can be life-saving, but leads to long-lasting side effects in childhood cancer survivors. The underlying mechanisms are not well known, and there are no established treatments to prevent or reverse these conditions. In the Blomgren research lab, our focus is to ameliorate the devastating cognitive deficits after radiotherapy to the juvenile brain, without compromising the treatment effect on the disease. In order to achieve this, the current project is using a novel research tool, the proprietary Ionis antisense oligonucleotides (ASOs), which was awarded the Breakthrough Prize 2019 for its application in spinal muscular atrophy in children. Previous work of our group has revealed a microglia-driven multiphasic inflammatory response after irradiation. Using the ASO technique, our goal is to modulate the microglia activity, abrogate the toxic inflammation and change the degenerative microenvironment after cranial irradiation. The method is tested in a mouse model of cranial radiotherapy, but the goal is to perform a clinical study. The target-specific ASOs have a favourable safety profile and have been approved by the FDA for use in humans. Main techniques used: Animal radiation, icv injections, bulk and single cell RNA seq, qPCR, western blot, immunohistochemistry, confocal microscopy. |