Non-mammalian growth factor formulations for human nervous system regenerative medicine

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

Humans and other mammals have limited ability to regenerate nerves and replace injured or damaged neurons. In contrast, other vertebrates are endowed with superior capacity to regenerate multiple organs; among tetrapods, aquatic salamanders such as newts and axolotls, have the largest regenerative spectrum. For example, urodele amphibians such as the axolotl (Ambystoma mexicanum) are endowed with the capacity to add new neurons to the brain throughout life [1], regenerate peripheral nerve injuries [2] and spinal cord after mechanical injury [3, 4]. Recent advances in understanding the regenerative and developmental processes in salamanders have a crucial role in being able to drive forward regeneration in human mammals.

The aim of this project therefore is to develop new medicines to treat human nervous system disorders based on non-mammalian growth factors. Specifically, we intend to combine new advances in understanding regeneration inspired by salamanders with advanced pharmaceutical technologies to treat nervous system disorders. We will: (i) identify non-mammalian growth factors associated with excellent regeneration in axolotl which are effective in human cell lines; (ii) fabricate controlled release formulations with identified biocompatible growth factors and (iii) assess pro-regenerative impact of formulations in vitro.

References:

[1] Maden M, Manwell LA, Ormerod BK. Proliferation zones in the axolotl brain and regeneration of the telencephalon. Neural Development. 2013;8:1.
[2] Uckermann O, Hirsch J, Galli R, Bendig J, Later R, Koch E, Schackert G, Steiner G, Tanaka E, Kirsch M. Label-free imaging of tissue architecture during axolotl peripheral nerve regeneration in comparison to functional recovery. Scientific Reports. 2019;9:12641.
[3] Amamoto R, Lopez Huerta VG, Takahashi E, Dai G, Grant AK, Fu Z, Arlotta P. Adult axolotls can regenerate original neuronal diversity in response to brain injury. eLife. 2016; 5: e13998.
[4] Joven A, Simon A. Homeostatic and regenerative neurogenesis in salamanders. Progress in Neurobiogy. 2018; 170: 81-98.

Project aligned to Predictive Pharmaceutical Sciences and Advanced Product Design

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023054/1 01/10/2019 31/03/2028
2283847 Studentship EP/S023054/1 01/10/2019 30/04/2021 Catherine Emma Bastin