Using Dual GLP-1/GIP Receptor Agonists to Treat Brain Insulin Resistance, Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Tech ID: tal000941

 

Introduction

 

Alzheimer’s disease (AD) poses one of the great challenges to 21st century medicine. It is the 6th leading cause of death in the US and after more than a century since its discovery, there are still no clinically effective treatments for AD that substantially slow or stop its progression. If the current situation persists, it is estimated that the number of AD dementia cases in the US will rise from 5.2 million today to 13.8 million by 2050, surging health care costs. There is consequently an urgent need for discovery of treatments markedly slowing AD progression. It has been estimated that disease-modifying treatments delaying onset of AD dementia by just 5 years could reduce the number of cases by 57% and reduce Medicare costs by 45%. 

 

Technology Description

 

• The invention is the new use of an antidiabetic agent in a phase II clinical trial as a treatment for brain insulin resistance in general and more specifically as a treatment for mild cognitive impairment (MCI) and the disorder to which it often leads, AD dementia. This invention stems from their research establishing that the brain in MCI and AD dementia is commonly and markedly insulin resistant even in the absence of diabetes. The invention proposes a novel therapeutic agent for AD dementia with an established safety profile.

 

• The compositions comprise using dual glucagon-like peptide 1 (GLP-1)/ gastric inhibitory peptide (GIP) receptor agonists. These are the only drugs of any type known to do all of the following:

 

1. Substantially reduce insulin resistance brains from an AD mouse model, MCI cases, and AD dementia cases

 

2. Markedly reduce many AD-related brain pathologies, as well as synaptic dysfunction and cognitive deficits in a mouse model of AD

 

3. Halt decline in glucose metabolism in AD dementia cases.

 

Stage of Development

 

Inventors have completed ex vivo stimulation experiments testing the response of the human hippocampal formation to 1nM insulin with or without a one hour pretreatment with a dual GLP-1/GIP receptor agonist. They have complete data of this type on 10 normal, 10 non-amnestic MCI, 10 amnestic MCI, and 10 AD dementia cases.

 

Advantages/Novelty

 

There is a continuing absence of highly effective AD treatments. The FDA has approved 6 drugs for AD treatment yet, despite being significant, the effects of all of these are only marginal and none substantially reduce its symptoms or its progression. This invention demonstrates potential to be the first effective treatment of AD. 

 

Applications

 

The GLP-1/GIP agonist tested can be repurposed as a drug for MCI and AD dementia. The agent has already gone through phase 1 and phase 2 clinical trials for diabetes, which will greatly strengthen the development path with an established safety profile.

 

Intellectual Property

 

US provisional patent application filed.

 

Patent Information:
For Information, Contact:
Wenyue Du
Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Konrad Talbot
Hoau-Yan Wang
Keith Black
Keywords:
Neurosciences