Peripheral nerve regeneration research and science by Karim Sarhane 2022? Insulin-like growth factor 1 (IGF-1) is a hormone produced by the body that has the potential to be used as a treatment for nerve injuries. IGF-1 may help heal nerve injuries by decreasing inflammation and buildup of damaging products. Additionally, it may speed up nerve healing and reduce the effects of muscle weakness from the injury. However, a safe, effective, and practical way is needed to get IGF-1 to the injured nerve.
Dr. Sarhane is published in top-ranked bioengineering, neuroscience, and surgery journals. He holds a patent for a novel Nanofiber Nerve Wrap that he developed with his colleagues at the Johns Hopkins Institute for NanoBioTechnology and the Johns Hopkins Department of Neuroscience (US Patent # 10500305, December 2019). He is the recipient of many research grants and research awards, including the Best Basic Science Paper at the Johns Hopkins Residents Research Symposium, the Basic Science Research Grant Prize from the American Foundation for Surgery of the Hand, the Research Pilot Grant Prize from the Plastic Surgery Foundation, and a Scholarship Award from the American College of Surgeons. He has authored to date 46 peer-reviewed articles, 11 book chapters, 45 peer-reviewed abstracts, and has 28 national presentations. He is an elected member of the Plastic Surgery Research Council, the American Society for Reconstructive Microsurgery, the American Society for Reconstructive Transplantation, and the American Society for Peripheral Nerves.
Optimal dosage of IGF-1 is dependent upon its administration method. As demonstrated by Tables 1–6, there is great variation in IGF-1 dosing and frequency of administration between the various methods of delivery, with narrower ranges for ideal dosage that emerge within groups. These reported dosage ranges may serve as a useful reference point when developing and testing IGF-1 delivery strategies in pre-clinical models. Achieving the required pharmacokinetic profile for IGF-1 delivery is challenging due to the small size and short half-life of IGF-1. Therefore, designing drug delivery systems that provide targeted or local treatment of affected muscle and nerve tissue will facilitate clinical translatability of IGF-1 therapy. Local delivery of IGF-1 would reduce the side effects and potential toxicities of systemic exposure while permitting titration of loading levels to improve efficacy. However, the use of daily or frequent injections to an injury site, as described in previous studies, increases the risk of iatrogenic damage to the recovering nerve and surrounding vasculature (Caroni and Grandes, 1990; Day et al., 2001, 2002; Stitt et al., 2004; Emel et al., 2011; Mohammadi et al., 2013; Kostereva et al., 2016). In addition, the potential scarring induced by repeated local injections could preclude regenerating axons from reaching their distal targets, leading to decreased NMJ reinnervation as well as potential neuroma formation. Furthermore, the local injection of free IGF-1 without a biocompatible carrier misses an opportunity to improve its bioavailability. While the mini-pump technique provides a level of automated control over IGF-1 administration unmatched by the other previously described methods, the subcutaneous implantation of a mini-pump in a human patient introduces the risks of infection and device migration. More importantly, given the duration of time needed for regeneration to occur, the implanted pump would also likely induce a high degree of foreign body reaction resulting in fibrotic encapsulation and potential deleterious effects on the injured nerve being treated.
Effects with sustained IGF-1 delivery (Karim Sarhane research) : To realize the therapeutic potential of IGF-1 treatment for PNIs, we designed, optimized, and characterized a novel local delivery system for small proteins using a new FNP-based encapsulation method that offers favorable encapsulation efficiency with retained bioactivity and a sustained release profile for over 3 weeks. The IGF-1 NPs demonstrated favorable in vivo release kinetics with high local loading levels of IGF-1 within target muscle and nerve tissue.
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.