Duo Xu, University of California, Los Angeles
Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration
Written by Jessalyn Low Hui Ying
Nerve growth factors (NGF) are promising therapeutic agents for the treatment of central nervous system (CNS) injuries as they stimulate the proliferation and differentiation of neurons. However, the delivery of NGF to CNS is a great challenge, primarily due to the blood-brain barrier (BBB) which is a highly restrictive barrier. To address this challenge, Duo Xu and his research team took inspiration from brain biology and identified a molecular analogue, 2-methacryloyloxyethyl phosphorylcholine (MPC), which is structurally similar to the neurotransmitter acetylcholine and its precursor, choline. More importantly, MPC could also similarly interact with nicotinic acetylcholine receptors (nAChRs) and choline transporters (ChTs), therefore, may be exploited to deliver NGF across the BBB to the CNS by hijacking of the receptor/transporter pathway.
With this knowledge, the researchers designed a nanocapsule consisting of MPC monomers and polylactic acid-based crosslinkers for the encapsulation of NGF. Upon intravenous injection of these NGF nanocapsules to mice, transmission electron microscopy imaging of the cerebrospinal fluid (CSF) indicated the presence of nanocapsules. Using enzyme-linked immunosorbent assay, NGF was also observed in the brain and spinal cord tissues, indicating that the NGF nanocapsules have successfully penetrated the BBB and entered the CNS to infiltrate the brain and spinal cords. Furthermore, NGF nanocapsules were demonstrated to exhibit therapeutic effect in CNS injuries. Mouse models with compression-induced spinal cord injury showed significant functional recovery after two weeks of treatment. Neurofilaments were observed to have infiltrated the injury site, demonstrating the successful delivery of NGFs.
“Given the prevalence of CNS diseases and injuries such as Alzheimer's, Parkinson's, and stroke, our delivery platform offers an entry point for therapeutic molecules to access their molecular targets in the CNS,” says Xu.