NeuroHope Therapeutics, Inc. - Technology
Technology:
Therapeutics, Inc.’s core technology is a multi-functional polymeric nanoparticle drug delivery system invented by our Chief Scientific Officer, Dr. Jeoung Soo Lee. This technology is protected by US patent # 10,232,050 B1 “Multi-functional particles and methods of using the same” assigned to Clemson University. NeuroHope has entered into an exclusive option license agreement to investigate development and commercialization.
Our proprietary carrier is an amphiphilic graft copolymer, poly (lactide-co-glycolide-graft-polyethylenimine) [PLGA-graft-PEI or PgP]. In water, PgP spontaneously self-assembles into polymeric micelles comprised of a hydrophobic PLGA core and cationic, hydrophilic PEI outer shell. Hydrophobic drugs can be loaded into the PLGA core at concentrations far exceeding their normal solubility. The PEI outer shell can form polyelectrolyte complexes with a wide range of therapeutic nucleic acids, including plasmid DNA, mRNA, siRNA, miRNA, or antisense oligonucleotides, protecting them from degradation and increasing cellular uptake. Amine groups in the PEI outer shell allow the covalent conjugation of antibodies and cell adhesion molecules to target the micellar carrier to specific cells.
Our proprietary carrier is an amphiphilic graft copolymer, poly (lactide-co-glycolide-graft-polyethylenimine) [PLGA-graft-PEI or PgP]. In water, PgP spontaneously self-assembles into polymeric micelles comprised of a hydrophobic PLGA core and cationic, hydrophilic PEI outer shell. Hydrophobic drugs can be loaded into the PLGA core at concentrations far exceeding their normal solubility. The PEI outer shell can form polyelectrolyte complexes with a wide range of therapeutic nucleic acids, including plasmid DNA, mRNA, siRNA, miRNA, or antisense oligonucleotides, protecting them from degradation and increasing cellular uptake. Amine groups in the PEI outer shell allow the covalent conjugation of antibodies and cell adhesion molecules to target the micellar carrier to specific cells.
Product, Application, and Technical Progress:
Our first product is a formulation consisting of the hydrophobic drug rolipram loaded into the PgP core (Rm-PgP). The first indication we are pursuing is acute spinal cord injury (SCI). One of the consequences of SCI is a sharp decline in cyclic adenosine monophosphate (cAMP) that plays critical roles in multiple cell types including activation status of inflammatory cells and regenerative potential of neurons. Rolipram acts to preserve / restore cAMP levels post-injury by inhibiting the phosphodiesterase IV (PDE IV) enzyme responsible for cAMP breakdown. Rolipram has a long history as a small molecule therapeutic for central nervous system disease, going through clinical trials as an anti-depressant. However, its clinical and commercial success has been limited by poor solubility and adverse side effects in the gastrointestinal system following systemic, oral delivery.
Our product, Rm-PgP, overcomes these challenges through a combination of local delivery via intrathecal injection and the ability of the PgP carrier to provide prolonged residence time at the site of delivery, allowing us to achieve local, sustained release at the site of injury while avoiding systemic side effects. In published studies, we have shown that local delivery of Rm-PgP at the SCI lesion epicenter restored cAMP levels and reduced secondary injury based on apoptosis and neuroinflammation in a rat severe compression SCI model (Macks 2018). We also demonstrated that a single injection of Rm-PgP at the SCI lesion improved motor function over 4 weeks and reduced secondary injury at 4 weeks post-injury (Gao 2023). In more recent preliminary data supported by NIH R01 grant, we have found that Rm-PgP administered by intrathecal injection in a rat moderate contusion SCI model 1) restored cAMP level up to 7 days, suggesting its capability for sustained, local drug delivery, 2) reduced neuroinflammation, reactive astrogliosis, and apoptosis, and 3) achieved motor functional recovery close to sham animal level; and slowed neuropathic pain development at 6 weeks post-injury. Our most compelling motor recovery studies, first performed in male rats, have been replicated with similar results in females. Rm-PgP has also been tested in a controlled cortical impact (CCI) traumatic brain injury (TBI) model. The acute outcomes evaluated in this study were consistent with our observations of Rm-PgP’s efficacy in SCI, including restoration / preservation of cyclic AMP levels and mitigation of secondary injury.
Our product, Rm-PgP, overcomes these challenges through a combination of local delivery via intrathecal injection and the ability of the PgP carrier to provide prolonged residence time at the site of delivery, allowing us to achieve local, sustained release at the site of injury while avoiding systemic side effects. In published studies, we have shown that local delivery of Rm-PgP at the SCI lesion epicenter restored cAMP levels and reduced secondary injury based on apoptosis and neuroinflammation in a rat severe compression SCI model (Macks 2018). We also demonstrated that a single injection of Rm-PgP at the SCI lesion improved motor function over 4 weeks and reduced secondary injury at 4 weeks post-injury (Gao 2023). In more recent preliminary data supported by NIH R01 grant, we have found that Rm-PgP administered by intrathecal injection in a rat moderate contusion SCI model 1) restored cAMP level up to 7 days, suggesting its capability for sustained, local drug delivery, 2) reduced neuroinflammation, reactive astrogliosis, and apoptosis, and 3) achieved motor functional recovery close to sham animal level; and slowed neuropathic pain development at 6 weeks post-injury. Our most compelling motor recovery studies, first performed in male rats, have been replicated with similar results in females. Rm-PgP has also been tested in a controlled cortical impact (CCI) traumatic brain injury (TBI) model. The acute outcomes evaluated in this study were consistent with our observations of Rm-PgP’s efficacy in SCI, including restoration / preservation of cyclic AMP levels and mitigation of secondary injury.