Atkinson, Emily; (2025) Peptide growth factor mimetics and therapeutic cell delivery for the treatment of central nervous system damage and disease. Doctoral thesis (Ph.D), UCL (University College London).

Text Emily_Atkinson_Thesis.pdf - Accepted Version Access restricted to UCL open access staff until 1 March 2026. Download (9MB)

Abstract

Central nervous system damage is a leading cause of disability and a global health priority, due to little spontaneous regeneration and limited treatments. Damage can be physical such as a traumatic brain injury, or caused by a neurodegenerative disease such as Parkinson’s disease, and can severely impact quality of life. Cell therapy is a promising approach to treating Parkinson’s disease by replacing lost or diseased dopaminergic neurons with cells that secrete dopamine and neurotrophic factors. The host immune response can limit therapeutic cell survival. Growth factor-based therapies can provide neuroprotection and improve outcomes for both damage and disease. However, the size, half-life and delivery limit clinical translation. Peptide growth factor mimetics have potential to overcome some limitations, with a decrease in size and more favourable pharmacokinetic properties. This work aimed to develop an immunomodulatory encapsulation system for delivering therapeutic cells and identify, synthesise and test novel peptide mimetics of growth factors. An immunomodulatory encapsulation system was successfully developed using a co-axial flow reactor to obtain alginate beads with a diameter < 200 µm. With the inclusion of tacrolimus-loaded microparticles, the number of T cells was reduced and therapeutic cell survival was increased in vitro, when encapsulated hiPSC-derived dopaminergic neuron progenitors were cocultured with T cells. Novel peptide mimetics of GDNF were successfully identified using computational alanine scanning mutagenesis, phage display and molecular docking. Peptides were synthesised using Fmoc solid-phase peptide synthesis and increased SH-SY5Y cell confluency. HPEDOCK2 was used to predict the binding site of the GDNF mimetics. Finally, a potent HGF mimetic was identified and an in vitro assay was developed which demonstrated that HGF was neuroprotective against glutamate-mediated excitotoxicity in embryonic rat cortical neurons. Overall, results indicated that therapeutic cell encapsulation systems and peptide growth factor mimetics are promising options in the treatment of central nervous system damage.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as XMLJSONCSV

Archive Staff Only

View Item