# The microtubule cytoskeleton as a novel target for cavernous nerve regeneration after prostatectomy

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $561,617

## Abstract

Abstract
 Radical prostatectomy (RP) is a commonly used treatment option for localized prostate cancer.
Unfortunately, the procedure carries a high risk of erectile dysfunction (ED) which is highly detrimental to the
post-surgical well-being of men. The main pathophysiological mechanism behind ED is damage to the cavernous
nerves (CN); mechanisms that regenerate or repair CN injury following RP could alleviate or treat ED in these
patients. The studies outlined in this proposal will pursue a novel approach to CN repair by harnessing the nerve
regenerative powers of Fidgetin-like 2 (FL2), a newly discovered microtubule regulator. In vitro studies indicate
that the depletion of FL2 strongly enhances axonal growth in primary cultures of rat peripheral nervous system
neurons. Recent work by the investigators involved in this proposal have shown that targeted depletion of FL2
via topical application of FL2-siRNA encapsulated in nanoparticles (FL2-siRNA-np) promotes the closure and
regeneration of cutaneous wounds in mouse models and improved erectile function outcomes in a rat model of
RP when applied at the time of CN injury. Remarkably, in a CN transection model of RP, at two weeks post
treatment with FL2-siRNA there is both improved erectile function outcomes and visible nerve regrowth. These
observations lead us to the hypothesis to be tested in this proposal that “following CN injury, depletion of FL2
activates mechanisms that promote cavernous nerve regeneration, leading to accelerated recovery of
erectile function”. This hypothesis will be tested in two specific aims.
 In the first Specific Aim we will substantiate our preliminary results that depletion of FL2 improves
recovery of erectile function following CN injury used as an animal model of RP. We will optimize formulation
and treatment regimens for ED. FL2-siRNA will be applied at the site of CN injury both at the time, and one week
following injury and recovery of erectile function determined by measuring the intracorporal pressure/blood
pressure ratio (ICP/BP) developed after CN stimulation, at various time points after treatment. Following
cavernosometry, we will perform pathology studies to provide evidence of CN regeneration and safety of the
different formulations.
 In the second Specific Aim we will conduct experiments to elucidate the mechanism by which the
depletion of FL2 promotes functional recovery after CN injury. We will determine the effects of FL2-siRNA on
axon growth and regeneration in vitro. Using tissues of controls and FL2-siRNA treated animals we will perform
extensive comparative histopathology and gene expression analyses on corporal tissue and from the site of
injury of treated versus control rats at various time-points after CN injury.
 Overall, upon completion of this proposal we will have established the potential of FL2 as a novel target
in repairing CN damage following RP, determined treatment regimens, formulation and safety considerations to
optimize potenti...

## Key facts

- **NIH application ID:** 9881275
- **Project number:** 5R01DK109314-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** KELVIN P DAVIES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,617
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881275

## Citation

> US National Institutes of Health, RePORTER application 9881275, The microtubule cytoskeleton as a novel target for cavernous nerve regeneration after prostatectomy (5R01DK109314-05). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9881275. Licensed CC0.

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