Targeted sustained delivery of IGF-1 for peripheral nerve injuries

The National Institute of Neurological Disorders and Stroke, a component of the Department of Health and Human Services National Institutes of Health, awarded a cooperative agreement to The Johns Hopkins University for $749,720 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853).

The funding supports development and preclinical testing of a sustained-delivery insulin-like growth factor 1 (IGF-1) therapeutic for peripheral nerve injuries. The recipient will establish small-scale good laboratory practice (GLP) testing and clinical-scale current good manufacturing practice (cGMP) manufacturing of a long-acting injectable IGF-1 delivery system comprising biodegradable nanoparticles embedded within a biocompatible nanofiber hydrogel composite. The work includes preclinical studies confirming biocompatibility, safety, and release profile in animal models, as well as pharmacokinetic, pharmacodynamic, and toxicology studies to assess metabolism, safety, and adverse effects and to define optimal and maximally tolerated doses for clinical trial design.

Work is performed in Baltimore, Maryland, with a period of performance from September 1, 2026 through August 31, 2028.

Abstract

Peripheral nerve injuries are a significant and serious issue causing permanent disability, pain, and reduced quality of life. Despite advancements in surgical techniques for nerve repair, functional outcomes remain poor as the slow rate of axon regeneration leads to the progressive, irreversible atrophy of denervated muscles and schwann cells. There are currently no FDA approved therapeutics to improve peripheral nerve regeneration and functional recovery. Insulin-like growth factor 1 (IGF-1) has the potential to improve nerve injury functional outcomes in a multimodal fashion by augmenting axonal regeneration while also maintaining muscle and schwann cell viability during long regeneration times. However, a major challenge in achieving therapeutic delivery is the protein's short half-life. Therefore, we have developed a long-acting injectable (LAI) to encapsulate IGF-1 into biodegradable nanoparticles that are then embedded within a biocompatible nanofiber hydrogel composite to provide sustained, local release of IGF-1. Our IGF-1 LAI drug delivery system has demonstrated sustained release over six weeks and produced a robust increase of 30% in functional recovery in small animal and non-human primate nerve injury models. In the proposed studies, we will build upon our robust preclinical work to bring the first truly effective therapy for peripheral nerve injuries to patients. To do this, we will first establish small scale GLP testing and clinical scale cgmp manufacturing. We will then confirm the biocompatibility, safety, and release profile of the cgmp IGF-1 LAI delivery system through preclinical studies in animal models. Pharmacokinetic, pharmacodynamic, and toxicology studies will be conducted to assess metabolism, safety, and potential adverse effects to define optimal and maximal tolerated doses and inform clinical trial design. Upon successful completion of preclinical studies, we will prepare and submit an investigational new drug (IND) application and initiate a phase i clinical trial for the IGF-1 LAI delivery system. The phase i clinical trial will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of the IGF-1 LAI in enhancing functional recovery following peripheral nerve injuries. Following completion of the clinical trial, we will seek to obtain breakthrough therapy designation from the FDA to expedite further development. Our novel bioengineered delivery system for IGF-1 presents not only significant potential as the first efficacious therapeutic for peripheral nerve injuries, but also as a breakthrough drug delivery system that enables continuous and precise administration of small protein therapeutics, such as growth factors, in a manner that is clinically practical, safe, and efficient.