Reconstructive transplantation research studies 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.
Although numerous studies have demonstrated the benefit of IGF-1 to SCs, myocytes, and neurons in vitro and following PNI in animal models, several factors must be examined prior to proposing a treatment modality that is suitable for clinical translation. Besides efficacy, additional considerations include ease of regulatory clearance and safety. With regard to regulatory clearance, GH, Growth Hormone Releasing Hormone, and IGF-1 are already clinically available, FDA-approved drugs approved for other indications. With regards to safety, hypoglycemia is the most commonly seen short-term effect of IGF-1 use, although accumulation of body fat, coarsening of facial features, and lymphoid hyperplasia necessitating surgical correction have also been observed with long-term use (Contreras et al., 1995; Tuffaha et al., 2016b). Clinical trials investigating a link between malignancy and exogenous GH therapy have been equivocal, with multiple studies in children undergoing GH therapy demonstrating a low risk of associated malignancy. Additionally, GH therapy in adults has not been found to increase the risk of cancer (Yang et al., 2004; Xu et al., 2005; Chung et al., 2008; Renehan and Brennan, 2008; Svensson and Bengtsson, 2009; Tuffaha et al., 2016b). Given the potential systemic effects of IGF-1, a practical delivery system that can provide sustained release of bioactive IGF-1 to nerve and muscle tissue affected by PNI is of great importance. It will also be important to determine the minimum dose and duration required to achieve therapeutic efficacy.
Effects with 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.
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.