Final Report Summary - IN-BRAIN (IN VIVO REPROGRAMMING: A NOVEL ROUTE TO BRAIN REPAIR)
Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and death of nerve cells. Since the adult brain has a very limited capacity for self-repair after the loss of neurons caused by such diseases or damage, there is an unmet need for finding new strategies to repair the brain.
The focus of my ERC project was to explore in situ conversion of resident glia as an alternative for generating new therapeutic neurons directly inside the brain. During the grant period we managed to provide the first proof-of-concept that resident astrocytes can be converted into neurons when converted in the brain. Since the original finding was reported, we have optimized the gene delivery methods, shown that both astrocytes and NG2 glia can be converted into neurons, and expanded the functional and molecular analysis of the resulting neurons. We have also developed new methods based on modified rabies virus tracing which allowed us to show that the in vivo converted neurons integrate into existing host circuitry.
This project has laid the foundation for a completely novel therapeutic strategy for neuronal replacement that is based on in vivo conversion of resident glial cells to new neurons directly in the brain. In the future, the results can lead to the development of alternative therapies for a large number of neurological disorders that involve neuronal cell loss such as Parkinson’s Disease, Huntingtons’s Disease, Epilepsy, Traumatic Brain Injury and Stroke.
The focus of my ERC project was to explore in situ conversion of resident glia as an alternative for generating new therapeutic neurons directly inside the brain. During the grant period we managed to provide the first proof-of-concept that resident astrocytes can be converted into neurons when converted in the brain. Since the original finding was reported, we have optimized the gene delivery methods, shown that both astrocytes and NG2 glia can be converted into neurons, and expanded the functional and molecular analysis of the resulting neurons. We have also developed new methods based on modified rabies virus tracing which allowed us to show that the in vivo converted neurons integrate into existing host circuitry.
This project has laid the foundation for a completely novel therapeutic strategy for neuronal replacement that is based on in vivo conversion of resident glial cells to new neurons directly in the brain. In the future, the results can lead to the development of alternative therapies for a large number of neurological disorders that involve neuronal cell loss such as Parkinson’s Disease, Huntingtons’s Disease, Epilepsy, Traumatic Brain Injury and Stroke.