New Prodrugs for Preventing and Treating Alzheimer's Disease

Technology No. 20180153
IP Status: PCT Patent Application Filed; Application #: PCT/US2019/040190

Improved pseudo-glutathione (ᴪ-GSH) for Alzheimer’s disease

New derivatives of pseudo-glutathione (ᴪ-GSH) can be used as prodrugs for potential Alzheimer’s disease (AD) treatment and prevention. The prodrugs and salts convert to ᴪ-GSH in plasma and show increased stability in the gastrointestinal tract and plasma. The prodrugs have demonstrated working memory restoration in mouse models of Alzheimer’s disease, and also have potential acetaminophen toxicity benefits. Already a strong candidate for treating Alzheimer’s disease and other neurodegenerative disorders, ᴪ-GSH is now an even stronger contender in the form of these stable new derivatives and salts.

Increased solubility, bioavailability and plasma stability

Pseudo-glutathione (ᴪ-GSH), an analog of an existing drug candidate, has been shown to reduce amyloid-β induced neurotoxicity and prevent cognitive decline in Alzheimer’s mouse models. These new orally bioavailable prodrugs act as sustained release form of ᴪ-GSH offering longer half-life and better cell penetration. The prodrugs improve upon the metabolic stability, solubility, cell permeability, bioavailability and plasma stability of ᴪ-GSH.

Phase of Development

  • In vitro and in vivo data. All compounds restored working memory in mice injected with Aβ peptide.

Benefits

  • Improved solubility, permeability, bioavailability and plasma stability of ᴪ-GSH
  • Improved stability in gastrointestinal tract and plasma
  • Helps prevent harmful glycation and Aβ plaque formation

Features

  • Salts convert to ᴪ-GSH in plasma
  • Resistant to oxidative metabolism
  • Targeted toward soluble amyloid aggregation toxicity evident in early AD
  • Can be used in combination with other treatments or independently
  • Antioxidant properties
  • Hepatoprotective qualities could treat acetaminophen toxicity

Applications

  • Neurodegenerative disorders (Alzheimer’s Disease)
  • Cognitive impairment
  • Acetaminophen toxicity


Researchers
Bob Vince, PhD
Director, Center for Drug Design
External Link (drugdesign.umn.edu)
Swati More, PhD
Assistant Professor, Center for Drug Design (CDD)
External Link (drugdesign.umn.edu)
Abbas Raza, PhD
Research Assistant Professor, Center for Drug Design (CDD)
External Link (drugdesign.umn.edu)

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