A GLP-1 Analog for the Treatment of ALS

Abstract

The involvement of neuroinflammation manifested by activated microglia and astrocytes in AL Sis supported by a wealth of clinical and molecular evidence. In addition to producing neurotoxic cytokines, activated microglia also induce differentiation of astroglial cells into neurotoxic A1 astrocytes - direct mediators of neuronal cell death, including possibly in ALS. Therefore, development of agents that could selectively inhibit the microglial activation and A1 astrocyte formation without off-target toxicity could have profound therapeutic potential since they could be used to treat a variety of neurologic disorders for which there currently are no disease-modifying therapies. NLY01 is a GLP-1R agonist. NLY01selectively inhibits microglial activation, and blocks induction of cytokines and A1astrocyte formation; thus, providing neuroprotection. The overall objective is to collect data for a FDA IND application for ALS. We propose to develop NLY01 for ALS by validating its potential as a target using both ALS animal and human ALS iPSC-based models.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2020
Accession Number
AD1106973

Entities

People

  • Nicholas J Maragakis
  • Seulki Lee

Organizations

  • Johns Hopkins University

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Animal Structures
  • Astrocytes
  • Blood-Brain Barrier
  • Cell Physiological Processes
  • Cells
  • Cytokines
  • Diseases And Disorders
  • Molecules
  • Motor Neurons
  • Neurodegeneration
  • Neuroglia
  • Neurons
  • Parkinson'S Disease
  • Proteins
  • Spinal Cord
  • Toxicity

Fields of Study

  • Medicine

Readers

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