Reconstructive transplantation research studies from Karim Sarhane in 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.
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.
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.
Recovery with sustained IGF-1 delivery (Karim Sarhane research) : We hypothesized that a novel nanoparticle (NP) delivery system can provide controlled release of bioactive IGF-1 targeted to denervated muscle and nerve tissue to achieve improved motor recovery through amelioration of denervation-induced muscle atrophy and SC senescence and enhanced axonal regeneration. Biodegradable NPs with encapsulated IGF-1/dextran sulfate polyelectrolyte complexes were formulated using a flash nanoprecipitation method to preserve IGF-1 bioactivity and maximize encapsulation efficiencies.
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.
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). Following surgical repair, axons often must regenerate over long distances at a relatively slow rate of 1–3 mm/day to reach and reinnervate distal motor endplates. Throughout this process, denervated muscle undergoes irreversible loss of myofibrils and loss of neuromuscular junctions (NMJs), thereby resulting in progressive and permanent muscle atrophy. It is well known that the degree of muscle atrophy increases with the duration of denervation (Ishii et al., 1994). Chronically denervated SCs within the distal nerve are also subject to time-dependent senescence. Following injury, proliferating SCs initially maintain the basal lamina tubes through which regenerating axons travel. SCs also secrete numerous neurotrophic factors that stimulate and guide axonal regeneration. However, as time elapses without axonal interaction, SCs gradually lose the capacity to perform these important functions, and the distal regenerative pathway becomes inhospitable to recovering axons (Ishii et al., 1993; Glazner and Ishii, 1995; Grinsell and Keating, 2014).