NATURE COMMUNICATIONS, 2021 · DOI: https://doi.org/10.1038/s41467-020-20112-4 · Published: January 13, 2021
Spinal cord injuries often lead to permanent disabilities because damaged nerve fibers fail to regenerate. This study found that delivering a designer cytokine called hyper-IL-6 (hIL-6) to motor neurons in the brain can promote significant recovery of hindlimb function after a complete spinal cord crush in mice. The researchers discovered that motor neurons modified with hIL-6 extend projections to serotonergic neurons in the brainstem. This allows the hIL-6 to be transported and released, stimulating regeneration of both corticospinal and raphespinal fibers. This method of transneuronal delivery enables the regenerative stimulation of neurons deep within the brainstem, which are difficult to access directly but are crucial for regaining function after a spinal cord injury.
Transneuronal delivery of highly potent molecules may be a promising strategy to achieve functional repair in the injured or diseased human CNS.
Regenerative stimulation of neurons located deep in the brain stem using highly potent molecules might be a promising strategy to achieve functional repair in the injured or diseased human CNS.
Combining hIL-6 with other strategies, such as neutralizing extracellular inhibitors at the lesion site or bridging the lesion site with permissive grafts, may further improve functional outcomes.