Use of Neuronal NOS Inhibitors for Alzheimer's Therapeutic Intervention

PROPOSED TITLE (cut & paste into Alternate Title): Use of Neuronal NOS Inhibitors for Alzheimer's Therapeutic Intervention

NU 2023-007

SHORT DESCRIPTION

A small molecule based approach that mitigates Alzheimer's neurodegeneration by inhibiting neuronal nitric oxide synthase to prevent tau phosphorylation and reduce Aβ oligomer formation.

• Richard Silverman*
  • Patrick G. Ryan/Aon Professor of Chemistry, Northwestern University, Weinberg College of Arts & Sciences
  • Department of Molecular Biosciences, Weinberg College of Arts & Sciences
  • Department of Pharmacology, Feinberg School of Medicine
  • Chemistry of Life Processes Institute
• Ha Do*
• Elizabeth Anne Johnson*
• William Klein*
• Vasu Dhananjayan

NU Tech ID: 2023-007

IP STATUS

US Patent pending (19/503,266)

DEVELOPMENT STAGE

TRL-3 Experimental Proof-of-Concept: Key functions have been validated in neuronal culture models.

BACKGROUND

Alzheimer's disease currently faces significant treatment challenges. Existing therapies do not fully address the complexity of neurodegeneration caused by soluble Aβ oligomers. The high costs and limited efficacy of current solutions underscore a clear unmet need for alternative intervention strategies.

ABSTRACT

This invention leverages a small molecule inhibitor of neuronal nitric oxide synthase to target multiple neurodegenerative pathways in Alzheimer's disease. In laboratory models, pre-treating neurons with the inhibitor prevented Aβ oligomer-induced tau phosphorylation, reduced Aβ oligomer formation from monomers, and increased synaptic spine density. The technology offers a promising approach by directly disrupting nNOS-dependent mechanisms associated with oxidative and nitrosative stress and inflammation.

APPLICATIONS

• Small molecule therapeutic for Alzheimer’s disease: Enables targeted intervention for neurodegeneration.
• Tool compound to study Alzheimer’s disease: Facilitates research into underlying disease mechanisms.

ADVANTAGES

• Small molecule: Exhibits straightforward pharmacokinetics and cost-effective synthesis.

PUBLICATIONS

• Ha Do, Elizabeth Anne Johnson, William Klein, Richard Silverman et al.,