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Recent Tech from SUNY Upstate

Small Molecule Inhibitors for Alzheimer's Immunotherapy
January 11, 2023

Pan-SHIP1/2 inhibitors enhance phagocytosis of dead neurons and amyloid beta by microglia. Backgrou...

Pan-SHIP1/2 inhibitors enhance phagocytosis of dead neurons and amyloid beta by microglia. Background: The beta-amyloid (1-42) peptide fragment is a crucial component of beta-amyloid debris that forms plaques in Alzheimer's Disease, playing a significant role in disease pathology and cognitive decline. Increased amyloid deposits and tau tangles exert chronic stress on microglia, leading to the emergence of "dark microglia" associated with pathological processes in Alzheimer's, including production of inflammatory cytokines, neurocytotoxicity, loss of neuronal synapses, and promotion of neuro-fibrillary tau tangles. However, microglia also have substantial homeostatic functions in the brain, which include pruning of synapses or phagocytic clearance of dead cells, cell debris, and beta-amyloid deposits. Technology Overview: The newly developed small molecule pan-SHIP1/2 inhibitors can modulate microglia activity in vivo, enhancing basal microglial homeostatic functions for therapeutic purposes in Alzheimer's disease. Specifically, the inhibitors, which were shown to be bioavailable in the central nervous system (CNS) in a mouse model, significantly increase phagocytosis of dead neurons and amyloid beta by microglia both in vitro and in vivo. The ability of these compounds to increase microglial and myeloid cell numbers in the CNS, while enhancing their capacity to remove beta-amyloid deposits, suggests that they could be used to reduce or reverse cognitive decline in Alzheimer's patients. Advantages: - Bioavailability in the CNS
- Immunotherapeutic approach Applications: - Alzheimer’s disease - Other dementias Intellectual Property Summary: Patent application submitted,

Licensing Potential: Development partner, Commercial partner, Licensing, Seeking investment Licensing Status: This technology is available for licensing. https://suny.technologypublisher.com/files/sites/istock-513688464.jpg  

Human Trabecular Organ-on-a-Chip Models
January 06, 2023

3D biomimetic hydrogel models of the trabecular meshwork of the eye, and a bioengineered system for ...

3D biomimetic hydrogel models of the trabecular meshwork of the eye, and a bioengineered system for modelling the conventional outflow tract. Background: Models of the trabecular meshwork have largely been 2D up until now, but research has shown that 2D models of the TM behave differently -- sometimes in complete opposition -- to 3D models. A 3D model better approximates the actual anatomy of the human tissue, permits more sophisticated experiments, and provides increased accuracy in data-gathering and therapy production to researchers. This trend applies to other models of the eye as well. Technology Overview: This technology is a 3D biomimetic hydrogel model of the trabecular meshwork (TM) of the eye, located on a microfluidics chip, intended to be used, for example, to study the relation between the mechanotransduction of the YAP/TAZ proteins and stiffening of the TM cells and extracellular matrix. Stiffening of the TM is associated with primary open angle glaucoma, the most common form of glaucoma. Figure 1 - Complete TM-on-a-chip setup Stage of Development: Technology Readiness Level (TRL) 3 - Analytical and experimental critical function and/or characteristic proof of concept. Bioengineered Human Trabecular Meshwork for Biological Applications This technology is "a system for modeling the conventional outflow tract." Also provided is a method for using the system for screening by contacting the cells with a known or suspected medicament and measuring its effects on the system such as flow of a perfusate. Also provided is a method of making the system by fabricating the porous substrate as a micropatterned scaffold. Figure 2 - An artistic rendering of a bi-layered "artificial TM"  Advantages: These two technologies more accurately approximate human 3D tissue anatomy with focus on the cell-ECM interface, and will permit more sophisticated research, clinically relevant drug screening and therapeutic testing, increased accuracy in data-gathering and drug production. Applications: Organ on a chip market and pharmaceutical testing for the eye. Intellectual Property Summary: Patent application submitted, Provisional 63/059,965 filed 7/31/20 US 16/044,806  Stage of Development: Technology Readiness Level (TRL) 6 - System/subsystem model or prototype demonstration in a relevant environment. Licensing Potential: Licensing, Commercial partner, Development partner Licensing Status: These technologies from SUNY Upstate Medical University and SUNY Polytechnic Institute respectively are available for licensing. https://suny.technologypublisher.com/files/sites/adobestock_94313718_(1).jpeg  

A Nanotrap to Improve Survival in Severe Sepsis by Attenuating Hyperinflammation Through H…
September 15, 2022

This optimized nanotrap therapy in combination with a moderate antibiotic treatment resulted in a 10...

This optimized nanotrap therapy in combination with a moderate antibiotic treatment resulted in a 100% survival rate in severe septic mice.  Background:
The mortality rates in severe sepsis patients are 3041%. In the U.S. alone, 1.7 million people develop sepsis on a yearly basis. Effective therapies to prevent or treat the cytokine storm or septic shock that often leads to mortality are lacking, with single mediator targets failing. With current treatments, conventional adsorption resins are made of hydrophobic polymers for nonspecific adsorption of biomolecules, for example, Cytosorb® for multiple cytokine adsorption. However, the spectrum of molecular adsorption in these cartridges is fixed by the chemistry of the resin, which appears insufficient in clinical trials. The management of hyperinflammatory reactions is as important as effective infection control in bacteremia sepsis, which is even critical for viral sepsis, given no effective antiviral drugs. The precise immune modulation is critical for sepsis treatment because of the dynamic and dysregulated immune system in patients Technology Overview:  
 In contrast to conventional absorption resins, researchers at SUNY Upstate Medical University have developed a hydrophilic, inert, and antifouling PEG-based PEGA resin for immobilization of versatile telodendrimer (TD) nanotrap (NT), which avoids cell adhesion. Researchers have discovered that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92–99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent.   https://suny.technologypublisher.com/files/sites/110-2025.jpeg Advantages:  
 This nanotrap technology is particularly effective for gram negative bacteria caused sepsis which makes up 50% of most sepsis cases. Providing efficient protein encapsulation with multiple charges and hydrophobic moieties on the dendritic periphery, the welldefined lineardendritic telodendrimer nanoplatform has precise and engineerable chemical structures for customized nanocarrier design in drug delivery. The 'octopus like' structure can be tailored in design, shape, structure and density based on the makeup of the lipopolysaccharide (LPS), enabling more efficient binding. Once put back into the body, the TD nanotrap will trigger the release of microphages to fight the rest of the infection, reduce swelling, and treat cytokine storm. Applications:  
 For treatment of sepsis caused by virus or bacteria.  Intellectual Property Summary:
https://patents.google.com/patent/WO2019051121A1/en?q=Compositions+Devices+Removal+Endotoxins+Cytokines&inventor=Juntao+Luo&oq=Juntao+Luo+Compositions+and+Devices+for+Removal+of+Endotoxins+and+Cytokines   Stage of Development:

  • The combination of the optimized NT therapy with a moderate antibiotic treatment resulted in a 100% survival rate in severe septic mice by controlling both infection and hyperinflammation, comp only 50–60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.
  • https://en.wikipedia.org/wiki/Technology_readiness_level
Additional Information:  
https://www.nature.com/articles/s41467-020-17153-0  
 

Antibody Against Inositol 1,4,5-Trisphosphate Receptor Type 2 (anti-IP3R antibody)
June 22, 2022

Antibody against the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) type 2  Background: The inos...

Antibody against the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) type 2  Background: The inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is an intracellular Ca²-release channel located on the endoplasmic reticulum (ER). IP3R2 is characterized by a high sensitivity to both IP3 and ATP and is biphasically regulated by Ca². Furthermore, IP3R2 is modulated by various protein kinases. In addition to its regulation by protein kinase A, IP3R2 forms a complex with adenylate cyclase 6 and is directly regulated by cAMP. Finally, in the ER, IP3R2 is less mobile than the other IP3R isoforms, while its functional properties appear dominant in heterotetramers. Technology Overview:  
Antibody against the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) type 2 Polyclonal, affinity-purified.  https://suny.technologypublisher.com/files/sites/2011-110.pngApplications:   

  • Western blot 
  • ELISA \Immunoprecipitation
  • Immunofluorescence assays