Title: A Nanotherapeutic Device for Brain Repair
Funder: Department of Health (England)

Abstract: Background The application of nanotechnology to healthcare - nano-medicine - is now recognised worldwide as a new era in clinical medicine. Currently untreatable illnesses including neurodegenerative diseases (NDD) present key future targets for nano-therapeutic intervention. Within the central nervous system (CNS) endogenous neural stem and precursor cells (NSC and NPC) constitute upto 10% of the brain, providing a natural resource to replenish damaged cells. This source of healthy cells can be exploited to replace diseased neural tissue by stimulation with neural growth factors. We have invented a nanotherapeutic device able to dramatically improve treatment of NDD by delivery of factors to both expand and protect neural progenitor cells. Aims Our overall longterm aims are structured towards technological improvements of our nano-device for treatment of NDD, initially focussing on Parkinson's Disease (PD). The Project has three main aims: [1] ADAPTATION OF OUR NANOTHERAPEUTIC DEVICE for expansion, protection and differentiation of human neural stem cells, neural progenitor cells, and of patient-fibroblast-derived induced pluripotent cells (iPC). [2] USE OF THE NEW DEVICES FOR IMPROVED CELL THERAPY FOR PD INCLUDING GROWTH FACTOR-NANO, AND/OR WNT5A-NANO FOR DOPAMINERGIC CELL DIFFERENTIATION. [3] DEVELOPMENT OF A NEURONAL PD MODEL using patient-derived iPC to identify disease-modyfing agents for delivery via nanotherapy. See ANNEX 3 FLOW CHART. Plan of Investigation Advanced bio-engineering technology will refine our current nano-delivery device that is already proven to be efficacious and non-toxic in vivo: pilot experiments using leukaemia inhibitory factor (LIF)-nanoparticles (LIF-nano) have shown LIF-nano-specific improvements in dopaminergic cell recovery from rats. Using LIF and other neurogenic growth factors we plan to demonstrate efficacy initially for PD [A] in expanding and protecting human NSC and NPC; [B] in guiding differentiation of NSC, NPC, and iPC towards specific lineages; and [C] protecting neural cells from disease processes. The device can deliver various, or multiple, factors for testing in human brain cell models. Choice of targeting antibody will optimise desired effects within complex cell populations. Potential Impact Neurological diseases of the brain represent the largest area of unmet clinical need in the Western world. There is no cure, nor can progression be slowed down. Proof of concept that NSC and NPC can be expanded using our nano-device to treat neurodegenerative disorders - including Alzheimer's and Parkinson's diseases that currently afflict over 500,000 people in the UK, costing the NHS ~ £10 billion/year - will bring huge rewards both in patient well-being and in economic value to the NHS. The commercial opportunities are great: pharmaceutical companies see the area as key for development. A substantial IP portfolio is anticipated. Clinical practice will be relieved and we anticipate self-administration of the device in future formulations designed to cross the blood brain barrier.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL