Novel immunotherapies for neurodegenerative diseases

The origin and progression of many neurodegenerative diseases is not clearly understood, and basic research is required to provide a platform for development of effective therapies.

Amyotrophic Lateral Sclerosis (ALS) is an incurable progressive disease of motor neurons in the spinal cord and brain, being associated with dysfunctional microglia.

The purpose of this research proposal is to address this unmet need using a dual therapeutic platform approach aiming to modulate the activity of disease-associated microglia.

Based on several years of our research into microglial biology and development of immunotherapies, the aim of our research programme is to develop novel immunotherapies including (i) enforced cellular repopulation of the CNS, in which we will replace microglia with transplanted healthy cells, and (ii) cuttimg-edge nanobiologics delivering specific immunomodulatory drugs that will specifically modify microglial function.

We will develop protocols for such therapies and investigate the immunomodulatory effects at molecular and functional levels in both in vitro brain organoid cell culture systems and in vivo in experimental models of ALS. We envisage that these therapeutic platforms will be applicable to a range of neurodegenerative diseases.

Not only will these platforms provide potential personalised immunotherapies for translation into the clinic but will also greatly increase our understanding of the molecular cues governing microglial colonization of the CNS.