Use of oncomodulin or combination of oncomodulin and cAMP analog for treating occular disorders and spinal cord injury
Inventors: Larry Benowitz, Yuqin Yin
Invention Types: Therapeutics
Research Areas: Neurology/Neuroscience, Ophthalmology
Keywords: ProteinFor More Information Contact: Caron, Connie
The inability of neurons in the mature central nervous system (CNS) to regenerate injured axons can have devastating consequences for victims of stroke, trauma, or certain neurodegenerative diseases. The optic nerve represents a classic paradigm of regenerative failure in the CNS. Inflammation can have both positive and negative effects in the CNS after injury. Dr. Benowitz's lab discovered that if macrophages and neutrophils are activated in the eye, retinal ganglion cells (RGCs) switch into an active growth state following injury and regenerate lengthy axons into the distal optic nerve.
Dr. Benowitz's lab identified a small Ca2+-binding protein, oncomodulin (Ocm), as a potent macrophage-derived growth factor that stimulates regeneration of injured axons in the optic nerve, a brain pathway in which regeneration does not normally occur. The lab showed that Ocm is expressed in the CNS as well as in macrophages and neutrophils (which are part of the body's innate immune system), binds directly to RGCs, and in low nanomolar concentrations, stimulates greater axon outgrowth from RGCs than other known trophic factors. Most significantly, Ocm promotes optic nerve regeneration in vivo, making it potentially useful therapeutically. Additionally, it is believed that the cAMP modulator and axogenic factor potentiates the activity of Ocm. Therefore if a cAMP modulator is further administered contemporaneously to the subject, an increase in the amount of regeneration may result.
Dr. Benowitz proposes the use Ocm or a combination of Ocm and cAMP analog to improve regeneration in the peripheral nervous system and the spinal cord. This is based on the discovery that when Ocm is applied to peripheral neurons in the dorsal root ganglia (DRG), the ability of these cells to grow axons when placed in culture a week later is greatly augmented. This result was published in Nature Neuroscience in 2006.
Ocm is also potentiated by PTEN deletion (Kurimoto et al, J. Neurosci 2010), and by counteracting extracellular inhibitors (Fisher et al., 2004 a, b).
Use of oncomodulin or combination of oncomodulin and cAMP analog to treat:
• Spinal Cord Injury
• Possibly neurodegenerative diseases or conditions
• Disease-induced peripheral neuropathy
• There is no treatment for spinal cord injuries.
• There is a strong need in the art for treatments of peripheral nerve damage (peripheral neuropathy).
• Available for exclusive or non-exclusive license
• Opportunity for sponsored research and co-development
Key Publications: Kurimoto T, Yin Y, Omura K, Gilbert HY, Kim D, Cen LP, Moko L, Kaegler S, Benowitz LI. Long-distance axon regeneration in the mature optic nerve: contributions of oncomodulin, cAMP, and pten gene deletion.
J Neurosci. 2010 Nov 17;30(46):15654-63. PMID:21084621
Related Publications: Yin Y, Cui Q, Gilbert HY, Yang Y, Yang Z, Berlinicke C, Li Z, Zaverucha-do-Valle C, He H, Petkova V, Zack DJ, Benowitz LI.
Oncomodulin links inflammation to optic nerve regeneration.
Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19587-92. Epub 2009 Oct 29. PMID: 19875691; |
Yin Y, Henzl MT, Lorber B, Nakazawa T, Thomas TT, Jiang F, Langer R, Benowitz
LI. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal
ganglion cells. Nat Neurosci. 2006 Jun;9(6):843-52. Epub 2006 May 14. PMID: 16699509.
IPStatus: Pat. Pend.