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By Kristy Tsang, on 25 October 2023
In this interview as part of the Early Career Researchers series, recognising the amazing translational work being done by postdocs and non-tenured researchers at UCL, Dr Jenny Lange highlights her Small Molecules Therapeutic Innovation Network (TIN) Pilot Data Scheme awarded project, developing a novel approach to treat genetic epilepsies.
The title of my project is ‘Targeting NF-kB signalling in genetic epilepsy astrocytes’. At the McTague lab, we are focused on creating human invitro models of Epilepsy of Infancy with migrating focal seizures (EIMFS), a rare developmental and epileptic encephalopathy caused by mutations in specific genes. Astrocytes, the most numerous glial cells in the CNS, have been shown to play a role in acquired epilepsy, but little is known of their contribution to genetic epilepsies.
I have differentiated induced pluripotent stem cells (iPSC) from healthy controls and children with EIFMS and found that EIMFS astrocytes showed increased activation of pro-inflammatory pathways. Using a repurposed small molecule drug, I wanted to investigate whether targeting NF-kB signalling specifically would be more beneficial to restoring astrocyte function than a general anti-inflammatory drug.
Children with EIFMS often experience developmental delays and difficulties, as well as responding poorly to existing anti-seizure medication. As such there is an unmet need for novel therapeutics. Targeting astrocytes has been shown to be beneficial in models of acquired epilepsy. Using bulk RNA sequencing, we identified a number of pro-inflammatory pathways that were significantly upregulated. Pro-longed neuro-inflammation can be detrimental to neuronal health and further worsen seizure activity. As such, modulating inflammatory phenotypes mediated by astrocytes could pose a promising therapeutic target.
I wanted to apply to the Small Molecules TIN Pilot Data Fund to test my hypothesis that specific inhibition of NF-kB could be beneficial for astrocyte function. As an early career researcher, it can be difficult to obtain funding to generate pilot data. The TIN fund was a great opportunity for me to take my research ideas further. Writing the grant proposal was also a really good learning opportunity that has prepared me for the process of writing larger grant applications.
I really enjoyed the process of applying for the TIN Pilot Data fund. The application form was very clearly laid out and helped me formulate my ideas into a coherent, concise plan. I attended the ACCELEEARE TIN pitch coaching session, which was a great experience and I got lots of feedback on how to best pitch my proposal.
With the support of the Small Molecule TIN grant, I have already generated some really interesting pilot data. I hope to expand upon these findings within the next couple of months and find out whether the data fits my hypothesis. I want to make the most of the funding I have received, and expand our knowledge of the role of astrocytes in genetic epilepsies.
My main research interest is the role astrocytes play in the pathology of childhood neurological diseases, and whether common pathways are involved. I hope that the data from this project will build the basis for other funding applications that will aid my move towards independence.
Jenny Lange is a research fellow at the Zayed Centre for Research into Rare Disease in Children. She is currently working at the McTague lab, investigating underlying mechanisms of genetic epilepsy using 3-dimensional spheroid models. Jenny is especially interested in the role of glial cells in childhood neurological diseases and how they contribute to neuronal dysfunction.
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