Chelation of zinc promotes nerve regeneration within the central nervous system
Inventors: Zhen Huang, Larry Benowitz, Paul Rosenberg, David Lippard, Yiqing Li
Invention Types: Therapeutics
Research Areas: Neurology/Neuroscience
Keywords: CNS, Neuropathy, New Indication/Use, Polymer, Small Molecule/Drug, Spinal Cord Injury, Stroke, TargetFor More Information Contact: Ives, Catherine L.
Following traumatic nerve injury, ischemic damage, or degenerative diseases such as glaucoma, projection neurons of the eye--the retinal ganglion cells (RGCs)--cannot regrow their axons and soon begin to die, leaving patients with lifelong visual losses. Past research has discovered ways to activate RGCs’ intrinsic growth capacity and counteract extracellular signals that normally inhibit axon growth in animal models. However, these methods do not fully arrest the slow loss of RGCs that persists after axonal injury, and even the cells that partially regenerate their axons are likely to be in a compromised state. The present invention concerns novel ways to both suppress cell death and strongly enhance the regeneration of injured axons.
Dr. Benowitz’s lab is working to identify cellular and molecular mechanisms that cause RGCs to die after axotomy, and establish ways to counteract these mechanisms, when combined with methods to promote axon regeneration, to restore meaningful levels of neuron regeneration and lost function.
Dr. Rosenberg's lab has elucidated zinc-dependent mechanisms of cell death in neurons and in oligodendrocytes, and the signaling pathways that are activated by elevation of intracellular free zinc and by oxidative stress. His lab continues to focus on basic mechanisms of cell death that are important in neurodegeneration and in white matter injury.
The two labs discovered that there is a rapid elevation of free zinc in the retina after the optic nerve has been injured, and that this zinc strongly inhibits neuronal survival and the regrowth of axons in an optic nerve injury model. Mitigation of this elevation in free zinc promotes regeneration of injured axons. These findings can be applied therapeutically, alone and in combination with other approaches, to disorders and diseases of the CNS caused by axonal injury such as spinal cord trauma, optic nerve injury, glaucoma, multiple sclerosis, stroke and CNS trauma.
The inventors envision an implantable device, or other means of delivering the therapeutic formulation, such as nanoparticles, for promoting regeneration in a lesioned nerve or tract within the central nervous system.
• Novel treatment to improve the survival of injured neurons and promote the regeneration of injured nerve fibers, primarily but not exclusively those located within the eye.
• Therapeutic delivery modalities to repair neural connections using these treatments.
• Potential to repurpose existing drugs to treat nerve damage.
• Potential to regrow axons in the optic nerve, or spinal cord, which to date have only been able to partially regenerate.
• Potential to be applied across the CNS.
• Potential for delivery to specific injured neurons.
Exclusive or non-exclusive license
Key Publications: Trakhtenberg EF, et al. Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury. Exp Neurol. 2018 Feb;300:22-29.
IPStatus: Pat. Pend.