Targeting Tryptophan Catabolism in Disease

Description:

Targeted repurposing of NK1-antagonists to decrease tryptophan catabolism

 

Market Need

 

Excess tryptophan catabolism has been implicated in diseases ranging from cardiovascular disease to Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s, and epilepsy. The essential amino acid tryptophan is catabolized through the kynurenine pathway where the kynurenine/tryptophan (KT) ratio is proportional to tryptophan catabolism. It has been found that metabolites of this pathway exhibit neurotoxic properties that may contribute to diseases of the central nervous system. Additionally, excess tryptophan catabolism could deplete the tryptophan needed for the biosynthesis of serotonin and contribute to diseases such as depression and sleep disorder. Thus, a drug that can inhibit tryptophan catabolism could hold great potential.

 

Technology Overview

 

The lab of Douglas and Rappaport have discovered that the FDA-approved NK1-antagonist Aprepitant causes a decrease in KT ratio in human subjects with HIV, suggesting that inhibition of tryptophan catabolism is a new mechanism of action for the drug.  The group has also been able to show that pro-inflammatory markers such as TNF-alpha and IL-6 were decreased after two weeks of treatment and that the markers increased once Aprepitant was discontinued. The group proposes that a personalized medicine approach of stratifying patients with high KT ratios to treat with Aprepitant can increase its efficacy.

 

Advantages

•       FDA-approved drug

•       Personalized medicine approach

Application

•       Potential treatment for cardiovascular disease, Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s, and epilepsy

•       Broad utility in diseases where tryptophan catabolism is increased

 

Stage of Development: In vivo proof of concept

 

Case ID:
0910-17-Douglas
Web Published:
2/23/2017
Patent Information:
Title Country Serial No. Patent No. File Date Issued Date
Modulation of Tryptophan Catabolism by NK1 Receptor Antagonists, and Methods of Use Thereof United States 62/370,486 8/3/2016  
Category(s):
Therapeutic
For Information, Contact:
Camille Jolly-Tornetta
Assistant Director
The Children's Hospital of Philadelphia
jollytornc@email.chop.edu
Inventors:
Steven Douglas
Serguei Spitsin
Jay Rappaport
Stephani Vesasquez
Keywords:
Personalized Medicine