Peptide Amphiphiles for Sonic Hedgehog Regulation of Pelvic Nerves for Treatment of Stress Urinary Incontinence and Erectile Dysfunction
NU 2018-075, 2018-076, 2018-077
INVENTORS
- Caroline Podlasek
- Kevin McVary
- Daniel Harrington
- Samuel Stupp*
SHORT DESCRIPTION
Novel peptide amphiphile (PA) nanofiber hydrogel is used to deliver sonic hedgehog (SHH) protein to nerves of the major pelvic ganglia and the rhabdospincter as a treatment for erectile dysfunction and urinary incontinence.
BACKGROUND
Urinary incontinence and erectile dysfunction affect a significant portion of older men, diabetic patients, and those treated for prostate cancer. Stress urinary incontinence (SUI) affects 72% of prostatectomy patients in the first week post-operation, largely due to surgical injury to the rhabdosphincter (RS) muscle, with long-term recovery difficulties impacting the patient’s quality of life. The cavernous nerve (CN) can also be injured during prostatectomy, leading to erectile dysfunction in up to 85% of patients. Subsequent downstream injury to other nerves within the major pelvic ganglia including the hypogastric (HYG) and pelvic (PN) nerves further contributes to SUI.
ABSTRACT
In collaboration with researchers from the University of Illinois, Southern Illinois University, and the University of Texas, Northwestern researchers developed a PA nanofiber hydrogel that contains SHH intercalated within the fibers of the gel. The SHH PA hydrogel allows for local delivery and sustained release of SHH to injured pelvic nerves and muscles. Application of SHH PA to the CN promotes nerve regeneration by increasing neurite growth, suggesting a potential treatment avenue for erectile dysfunction in aging, diabetic, or prostatectomy patients. Moreover, researchers found that SHH treatment induces neurite formation in the PN and HYG nerves and increases RS cell growth, indicating a therapeutic use of SHH PA for SUI prevention as well. The PA nanofiber hydrogels are biodegradable, offering a non-invasive and safe delivery method that eliminates the need for surgical removal.
APPLICATIONS
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Treatment of erectile dysfunction and SUI in aging, diabetic, and prostatectomy patients
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General peripheral nerve regeneration
ADVANTAGES
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Localized delivery of SHH protein to the CN and penile tissues
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Sustained release of SHH protein at the injury site over an extended period of time
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Easily applied to the injury site during surgery
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Biodegradable and minimally invasive application
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Adaptable to other neuropathies regulated by SHH
IP STATUS
Issued US Patent No. 11,426,448.
PUBLICATIONS
Martin, S. et al. (2021) Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction. Nanomedicine: Nanotechnology, Biology and Medicine, 37:102444.
Choe, S. et al. (2019) Optimization of sonic hedgehog delivery to the penis from self-assembling nanofiber hydrogels to preserve penile morphology after cavernous nerve injury. Nanomedicine: Nanotechnology, Biology and Medicine, 20:102033.
Dobbs, R. et al. (2018) Peptide amphiphile delivery of sonic hedgehog protein promotes neurite formation in penile projecting neurons. Nanomedicine: Nanotechnology, Biology and Medicine, 14(7):2087-94.
Choe, S. et al. (2017) Peptide amphiphile nanofiber hydrogel delivers sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunction. Nanomedicine: Nanotechnology, Biology and Medicine, 13(1):95-101.
Angeloni, N. L. et al. (2011) Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. Biomaterials, 32(4):1091-101.
SHH PA treatment enhances pelvic ganglia (PG) neuron regeneration and improves erectile function.
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