Reconstructive transplantation studies from Karim Sarhane 2022? Researchers at Johns Hopkins Hospital in Baltimore, MD, conducted a study to develop a drug delivery system using a very small material, nanofiber hydrogel composite, which can hold nanoparticles containing IGF-1 and be delivered near the injured nerve to help it heal. Dr. Kara Segna, MD, received one of three Best of Meeting Abstract Awards from the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) for the project. She will present the abstract “IGF-1 Nanoparticles Improve Functional Outcomes After Peripheral Nerve Injury” on Saturday, April 2, at 1:45 pm during the 47th Annual Regional Anesthesiology and Acute Pain Medicine Meeting being held March 31-April 2, 2022, in Las Vegas, NV. Coauthors include Drs. Sami Tuffaha, Thomas Harris, Chenhu Qui, Karim Sarhane, Ahmet Hoke, Hai-Quan Mao.
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) : We successfully engineered a nanoparticle delivery system that provides sustained release of bioactive IGF-1 for 20 days in vitro; and demonstrated in vivo efficacy in a translational animal model. IGF-1 targeted to denervated nerve and muscle tissue provides significant improvement in functional recovery by enhancing nerve regeneration and muscle reinnervation while limiting denervation-induced muscle atrophy and SC senescence. Targeting the multimodal effects of IGF-1 with a novel delivery.
Research efforts to improve PNI outcomes have primarily focused on isolated processes, including the acceleration of intrinsic axonal outgrowth and maintenance of the distal regenerative environment. In order to maximize functional recovery, a multifaceted therapeutic approach that both limits the damaging effects of denervation atrophy on muscle and SCs and accelerates axonal regeneration is needed. A number of promising potential therapies have been under investigation for PNI. Many such experimental therapies are growth factors including glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and brain-derived neurotrophic growth factor (Fex Svenningsen and Kanje, 1996; Lee et al., 2007; Gordon, 2009). Tacrolimus (FK506), delivered either systemically or locally, has also shown promise in a number of studies (Konofaos and Terzis, 2013; Davis et al., 2019; Tajdaran et al., 2019).
Research efforts to improve PNI outcomes have primarily focused on isolated processes, including the acceleration of intrinsic axonal outgrowth and maintenance of the distal regenerative environment. In order to maximize functional recovery, a multifaceted therapeutic approach that both limits the damaging effects of denervation atrophy on muscle and SCs and accelerates axonal regeneration is needed. A number of promising potential therapies have been under investigation for PNI. Many such experimental therapies are growth factors including glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and brain-derived neurotrophic growth factor (Fex Svenningsen and Kanje, 1996; Lee et al., 2007; Gordon, 2009). Tacrolimus (FK506), delivered either systemically or locally, has also shown promise in a number of studies (Konofaos and Terzis, 2013; Davis et al., 2019; Tajdaran et al., 2019).
