Protecting Neuronal Integrity
Targeting neuron-intrinsic mechanisms and the neuron-glia axis to protect neurons and preserve function.
Axon degeneration and neuronal loss are early hallmarks of several peripheral, central and ocular nervous system diseases. While axon degeneration is often an early and catastrophic event, regeneration is inefficient (slow in the peripheral nervous system and near-absent in the central nervous system). Consequently, halting axonal degeneration early has tremendous potential in the treatment of neurological diseases.
Seminal discoveries from the labs of Nura Bio’s scientific founders and advisors have revealed that a form of injury-activated axon degeneration, Wallerian degeneration, is controlled by a novel, druggable, axon-intrinsic metabolic pathway with putative axon-extrinsic immune function. Nura Bio’s early pipeline is focused on modulating targets that play a role in Wallerian degeneration for the treatment of neurological diseases.
SARM1 is an axon-intrinsic metabolic sensor and regulator with putative immune function, playing a central role in axonal degeneration. Recent groundbreaking research from the labs of Nura Bio co-founders Marc Freeman, PhD, and Steve McKnight, PhD, revealed that SARM1 is an injury-activated, prodegenerative NAD hydrolase that is a central switch in the Wallerian degeneration pathway, driving catastrophic degeneration upon injury. Consistent with these findings, knocking out SARM1 is neuroprotective, conferring both structural preservation (as evidenced by lower plasma Neurofilament Light levels, an emerging biomarker in neurological disorders) and functional preservation in several preclinical models of neurological disease.
We are developing small molecule inhibitors of SARM1 for the treatment of peripheral, central and ocular nervous system disorders.
Important as it is to prevent early degeneration, when degeneration and neuronal loss do occur, it is equally critical that the debris is efficiently cleared. Glial cells, the peripheral and central nervous system’s immune surveillance machinery, are recruited to clear dystrophic axons and neurons. Neuron-glia crosstalk that drives glial recruitment upon injury has now been shown to be dysregulated in neurological diseases with recent groundbreaking advances in human genetics bringing to the fore specific neuroimmune pathways and targets that are dysregulated in neurological diseases. Restoring the functioning of the neuron-glia axis to improve the nervous system’s immune surveillance capacity in response to neurological injury or disease is the second approach we are taking at Nura Bio to tackle neurological diseases.
End-to-end drug discovery engine with a line of sight to the clinic
Nura Bio’s fully integrated drug discovery and development team is rapidly advancing novel discoveries from target identification and validation through preclinical development to fuel an innovative pipeline of potentially life-saving medicines. Our research and development operations are housed in world-class laboratories in South San Francisco’s dynamic biotech cluster with access to sophisticated technologies in-house and at leading academic institutes in the Bay Area.