Peripheral nerve regeneration research from 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.
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.
Heparin is another upregulator of endogenous IGF-1 that was shown to be effective in promoting nerve and muscle recovery following PNI, as demonstrated by Madaschi et al. (2003) with intraperitoneal injection of a dosage of 1 mg/kg (Madaschi et al., 2003). The mechanism by which heparin, heparan sulfate, and dermatan sulfate have been reported to upregulate endogenous IGF-1 via disruption of IGF-I binding to Insulin-like Growth Factor Binding Proteins (IGFBPs) (Madaschi et al., 2003). Heparin is also thought to inhibit the binding of IGFBP-3 to extracellular matrix heparan sulfate proteoglycans, thereby reducing the affinity of IGFBPs for IGF-I administration and resulting in the release of IGFBP-3 from the cell surface (Gorio et al., 2001). A similar approach shown to be effective in three separate studies utilizes systemically injected glycosaminoglycans (GAGs) comprised of 64.4% heparin, 28.8% dermatan sulfate, and 6.7% chondroitin sulfate. The effectiveness of GAGs in enhancing the recovery process following PNI was evidenced by a marked increase in IGF-1 levels in denervated muscle, leading to enhanced recovery as measured by nerve-evoked muscle force testing and the extent of muscle reinnervation (Gorio et al., 1998, 2001; Losa et al., 1999).
Recovery by sustained IGF-1 delivery (Karim Sarhane research) : The translation of NP- mediated delivery of water-soluble bioactive protein therapeutics has, to date, been limited in part by the complexity of the fabrication strategies. FNP is commonly used to encapsulate hydrophobic therapeutics, offering a simple, efficient, and scalable technique that enables precise tuning of particle characteristics [35]. Although the new iFNP process improves water-soluble protein loading, it is difficult to preserve the bioactivity of encapsulated proteins with this method.
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.
