NSC-Reconstruct: an overview

NSC-Reconstruct: Novel Strategies for Cell-based Neural Reconstruction
 

Why NSC-Reconstruct?
The incidence of debilitating and incurable age-associated neurodegenerative diseases is on the rise world-wide as a result of our continuously increasing life expectancy. Our brain is an organ with limited regenerative capacity, there is little option to halt or repair the damage occurring to the brain of these patients. Current treatments for neurodegenerative disorders are therefore largely confined to tackle and alleviate symptoms but they do not prevent, slow down or repair the degenerative processes underlying neurodegenerative diseases. Stem cell technologies and cellular reprogrammming constitute promising future therapeutic options for repairing the damaged brain by replacing damaged neural cells and by reconstructing  circuits in the damaged brain. On the basis of the high prevalence of the most common neurodegenerative and neuro-impairment disorders (i.e. Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, stroke, traumatic brain injury, amyotrophic lateral sclerosis and multiple sclerosis), it is expected that such neural regenerative treatments will have the potential to reach out to millions of patients globally.
 
What NSC-Reconstruct is about?
NSC-Reconstruct project aims at repairing the damaged brain cells and reconstructing our brain circuits using neurons and reprogrammed cells, derived from stem cells. This type of cell-based strategy constitutes a very promising approach for the treatment of those neurodegenerative diseases where only a single and confined subtype of cells is damaged. This is the case of Parkinson’s disease, where promising preliminary results have been obtained using fetal cells for transplantation (Barker, 2015). Huntington’s disease is another example where the replacement of a single cell type is needed, and for which fetal tissue transplantations have been conducted and stem cell based therapies are actively being developed (Precious, 2017). European networks involving several partners from this consortium have been pioneers in the  development of stem cell-based therapies for PD and HD, and are leading a European pluripotent stem cell clinical trial for PD projected to start in 2020 (Barker, 2018).
 
Why NSC-Reconstruct is innovative?
In NSC-Reconstruct project, we will use the single cell replacement approach on Parkinson’s Disease and will replace dopamine-releasing cells at the site of grafting - the striatum. In parallel, we will work on repairing more complex cellular networks such as those affected in HD. We will then extend the assessment of circuit integration and functional repair of complex circuits of stem cell derived neurons grafted into the damaged cerebral cortex. This part of the brain is a of high clinical relevance given the number of diseases striking the cortex,  but where connections of multiple network hubs are necessary for effective repair. Although the cell-based repair strategies we propose to develop are at different stages of clinical development, with PD being the most advanced, collectively this work will provide the basis for new approaches aiming to compensate for the neuronal loss following acute injury or progressive neurodegenerative diseases of the brain.

We also expect that this work will have implications for an even wider number of repairing strategies for the brain, including indications where the loss of brain tissue is more extensive and includes diverse cell types, such as is the case in stroke and trauma. 

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