Reconstructive transplantation research and science by Karim Sarhane 2022? 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.

During his research time at Johns Hopkins, Dr. Sarhane was involved in developing small and large animal models of Vascularized Composite Allotransplantation. He was also instrumental in building The Peripheral Nerve Research Program of the department, which has been very productive since then. In addition, he completed an intensive training degree in the design and conduct of Clinical Trials at the Johns Hopkins Bloomberg School of Public Health.

Local administration of IGF-1 was achieved by several targeted approaches including direct application of free IGF-1 to the injured nerve at the time of surgical transection as well as single, periodic, and daily local injections of free IGF-1 to the injury site (Caroni and Grandes, 1990; Welch et al., 1997; Day et al., 2001, 2002; Stitt et al., 2004; Emel et al., 2011; García Medrano et al., 2013; Mohammadi et al., 2013; Gu et al., 2015; Kostereva et al., 2016; Table 4). Local injection of free IGF-1 is not practical for clinical application as the half-life of IGF-1 is 10 min while the time required for regeneration to occur is often many months (Mayocliniclabs.com, 2020). Multiple injections per day would thus be required to maintain local tissue concentrations. We therefore did not attempt to ascertain the optimal dosages for this approach.

Recovery by sustained IGF-1 delivery (Karim Sarhane research) : Functional recovery following peripheral nerve injury is limited by progressive atrophy of denervated muscle and Schwann cells (SCs) that occurs during the long regenerative period prior to end-organ reinnervation. Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and SCs. Achieving sustained, targeted delivery of small protein therapeutics remains a challenge.

The amount of time that elapses between initial nerve injury and end-organ reinnervation has consistently been shown to be the most important predictor of functional recovery following PNI (Scheib and Hoke, 2013), with proximal injuries and delayed repairs resulting in worse outcomes (Carlson et al., 1996; Tuffaha et al., 2016b). This is primarily due to denervation-induced atrophy of muscle and Schwann cells (SCs) (Fu and Gordon, 1995).

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.