Best rated peripheral nerve regeneration research and science by Karim Sarhane
Reconstructive transplantation research from 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.
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.
The neurotrophic effects of IGF-1 have been found to be dose-dependent and independent of cell-cycle stage (Sumantran and Feldman, 1993; Tuffaha et al., 2016b). Specific trophic benefits to neurons include the promotion of neurite outgrowth, prevention of neuronal apoptosis, and the promotion of growth cone motility. As the proximal end of an injured nerve begins to recover, regenerating axons are guided to reinnervate their distal targets by numerous chemotrophic factors, resulting in the formation of a growth cone. IGF-1 plays a key role in the motility of the growth cone by inducing reorganization of actin and activation of focal adhesion molecules via the PI3K/Akt pathway (Tuffaha et al., 2016b). IGF-1 further augments growth cone motility via downregulation of c-myc, a cell proliferation transcription factor indicative of neuronal differentiation, and upregulation of growth cone-associated protein 43 (GAP-43), a vital component of neurite formation.
Effects by 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.
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.
Insulin-like growth factor-1 (IGF-1) is a particularly promising candidate for clinical translation because it has the potential to address the need for improved nerve regeneration while simultaneously acting on denervated muscle to limit denervation-induced atrophy. However, like other growth factors, IGF-1 has a short half-life of 5 min, relatively low molecular weight (7.6 kDa), and high water-solubility: all of which present significant obstacles to therapeutic delivery in a clinically practical fashion (Gold et al., 1995; Lee et al., 2003; Wood et al., 2009). Here, we present a comprehensive review of the literature describing the trophic effects of IGF-1 on neurons, myocytes, and SCs. We then critically evaluate the various therapeutic modalities used to upregulate endogenous IGF-1 or deliver exogenous IGF-1 in translational models of PNI, with a special emphasis on emerging bioengineered drug delivery systems. Lastly, we analyze the optimal dosage ranges identified for each mechanism of IGF-1 with the goal of further elucidating a model for future clinical translation.