Peripheral nerve regeneration research and science with Karim Sarhane today? 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.
Optimal dosage of IGF-1 is dependent upon its administration method. As demonstrated by Tables 1–6, there is great variation in IGF-1 dosing and frequency of administration between the various methods of delivery, with narrower ranges for ideal dosage that emerge within groups. These reported dosage ranges may serve as a useful reference point when developing and testing IGF-1 delivery strategies in pre-clinical models. Achieving the required pharmacokinetic profile for IGF-1 delivery is challenging due to the small size and short half-life of IGF-1. Therefore, designing drug delivery systems that provide targeted or local treatment of affected muscle and nerve tissue will facilitate clinical translatability of IGF-1 therapy. Local delivery of IGF-1 would reduce the side effects and potential toxicities of systemic exposure while permitting titration of loading levels to improve efficacy. However, the use of daily or frequent injections to an injury site, as described in previous studies, increases the risk of iatrogenic damage to the recovering nerve and surrounding vasculature (Caroni and Grandes, 1990; Day et al., 2001, 2002; Stitt et al., 2004; Emel et al., 2011; Mohammadi et al., 2013; Kostereva et al., 2016). In addition, the potential scarring induced by repeated local injections could preclude regenerating axons from reaching their distal targets, leading to decreased NMJ reinnervation as well as potential neuroma formation. Furthermore, the local injection of free IGF-1 without a biocompatible carrier misses an opportunity to improve its bioavailability. While the mini-pump technique provides a level of automated control over IGF-1 administration unmatched by the other previously described methods, the subcutaneous implantation of a mini-pump in a human patient introduces the risks of infection and device migration. More importantly, given the duration of time needed for regeneration to occur, the implanted pump would also likely induce a high degree of foreign body reaction resulting in fibrotic encapsulation and potential deleterious effects on the injured nerve being treated.
Recovery 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.
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.
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.