SARM1 inhibition as a novel therapeutic strategy for Cln1 disease

2019 Pilot Project Read More


Principal Investigator: Aaron DiAntonio (WashU Developmental Biology)
Collaborator: Jonathan Cooper (WashU Pediatrics), Mark Sands (WashU Medicine)


Neuronal ceroid lipofuscinosis is a fatal genetic disorder that kills children. Its infantile form, also called CLN1 disease has a devastating effect upon the brains of these children. Previous attempts to treat CLN1 disease have proved only partly effective. This is likely because there are underappreciated effects of disease upon the rest of the body that we failed to treat. This includes the nerve fibers, or axons, that control our movements and help us sense the environment. We have recently found that these axons are eliminated as CLN1 disease gets worse. Blocking this axonal pathology is anticipated to provide a more effective treatment for CLN1 disease. Because we know one of the key mechanisms by which axons are lost in many neurodegenerative diseases, we will now test if we are able to block this mechanism in a model of CLN1 disease. We will do this in two different ways, first genetically to gain proof of principle that this strategy may be beneficial. Secondly, we will use gene therapy to specifically suppress axon degeneration. At the end of these experiments we will know whether we can rescue this newly identified axonal feature in a model of CLN1 disease. This will also lend further support for how blocking axon degeneration may be a treatment for other neurodegenerative diseases.


Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.

Aaron DiAntonio

Jonathan Cooper

Mark Sands