Neuronal loss/destruction is the leading cause of symptoms in patients suffering from neural injury or neurodegenerative disorders.

Following neural insult astrocytes proliferate and become active glial cells to form glial scarring in order to protect neighboring tissue from further damage.

The downside to this scarring is the inhibition of neuronal growth and synaptic transmission which would allow for the recovery following the insults mentioned above.

 Recent research from Penn State University has resulted in a protocol involving four small molecules that together can efficiently program astrocytes into fully fuctional nerons. In vitro SB431542 5 micromolar, LDN193189 0.25 micromolar, CHIR99021 1.5 micomolar and DAPT 0.25 micromolar added to astrocytes led over six days to a neuronal yield (converted neurons/astrocyte) of 71%!



Furthermore the drug converted human neurons could survive 3-7 months in culture and form robust synaptic connections.

Even more impressive is the in vivo obsevations that intracranial injection in to the mouse hippocampus or intraperitoneal injections over three weeks both yielded significant neurogenesis. The data from the IP injection suggests that the molecules cross the mouse blood brain barrier and with some suitable medicinal chemistry these compounds could be formulated and administered IP or even orally for the treatment of such diseases as stroke, Dementia or spinal injury.

reference

https://doi.org/10.1016/j.stemcr.2019.01.003