Plastic surgery research by Karim Sarhane right now? We performed a study with rodents and primates that showed this new delivery method provided steady release of IGF-1 at the target nerve for up to 6 weeks,” Dr. Karim Sarhane reported. Compared to animals without this hormone treatment, IGF-1 treated animals (rodents and primates) that were injected every 6 weeks showed a 30% increase in nerve recovery. This has the potential to be a very meaningful therapy for patients with nerve injuries. Not only do these results show increased nerve recovery but receiving a treatment every 6 weeks is much easier on a patient’s lifestyle than current available regiments that require daily treatment.
Dr. Karim Sarhane is an MD MSc graduate from the American University of Beirut. Following graduation, he completed a 1-year internship in the Department of Surgery at AUB. He then joined the Reconstructive Transplantation Program of the Department of Plastic and Reconstructive Surgery at Johns Hopkins University for a 2-year research fellowship. He then completed a residency in the Department of Surgery at the University of Toledo (2021). In July 2021, he started his plastic surgery training at Vanderbilt University Medical Center. He is a Diplomate of the American Board of Surgery (2021).
Gene delivery targeted to skeletal myocytes has also demonstrated promise as a method of upregulating IGF-1 production in PNI models (Flint et al., 2004; Rabinovsky and Draghia-Akli, 2004; Nagata et al., 2014; Tsai et al., 2016). This approach has been applied both systemically as well as directly to the local site of PNI. Amongst the gene delivery protocols included in Table 2, the work of Nagata et al. (2014) is notable given its use of a biocompatible polyplex nanomicelle as a means of delivering IGF-1 plasmid DNA (pDNA) to the local site of PNI (Nagata et al., 2014). The diverse strategies employed by these systemic GH axis modifiers demonstrate the flexibility with which IGF-1 can potentially be incorporated into future translational approaches. However, these systemic therapeutic approaches are all limited by the resulting systemic upregulation of IGF-1 with the associated risks and side effects as well as the lack of fine control of IGF-1 levels within the target tissues, specifically the injured nerve and denervated muscle.
Effects with sustained IGF-1 delivery (Karim Sarhane research) : Under optimized conditions, uniform PEG-b-PCL NPs were generated with an encapsulation efficiency of 88.4%, loading level of 14.2%, and a near-zero-order release of bioactive IGF-1 for more than 20 days in vitro. The effects of locally delivered IGF-1 NPs on denervated muscle and SCs were assessed in a rat median nerve transection-without- repair model. The effects of IGF-1 NPs on axonal regeneration, muscle atrophy, reinnervation, and recovery of motor function were assessed in a model in which chronic denervation is induced prior to nerve repair. IGF-1 NP treatment resulted in significantly greater recovery of forepaw grip strength, decreased denervation-induced muscle atrophy, decreased SC senescence, and improved neuromuscular reinnervation.
Peripheral nerve injuries (PNIs) affect approximately 67 800 people annually in the United States alone (Wujek and Lasek, 1983; Noble et al., 1998; Taylor et al., 2008). Despite optimal management, many patients experience lasting motor and sensory deficits, the majority of whom are unable to return to work within 1 year of the injury (Wujek and Lasek, 1983). The lack of clinically available therapeutic options to enhance nerve regeneration and functional recovery remains a major challenge.
Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.