Cellular ‘Soap’ For Infectious Disease Accelerated Aging
Featured Project

Cellular ‘Soap’ For Infectious Disease Accelerated Aging

Senescence
Pathogens
Ageing
Prevention of communicable disease via hygiene, antibiotics, vaccines and other innovations has provided the largest life expectancy gains in human history. It is increasingly appreciated that pathogens can age humans by driving cell senescence. Dr. Peterson has identified chemistry that acts as a cellular ‘soap’ to concomitantly thwart pathogens and senescent cells.
Licensing OutreachView project
Investment
$ 231,000
Initiated
10.5.2022
Approval
57.81% Voted Yes
Project Details
Tim Peterson
Research Lead
Dr. Roland Dolle
Medicinal Chemist
AT A GLANCE
Stage
Early stage preclinical discovery
Area
Drug discovery
Status
Ongoing
Patent
Not filed yet

Background

Senolytics have emerged as an intriguing new therapeutic paradigm for aging-related disease. Numerous senolytics have been identified which selectively kill pathogenic senescent cells without harming proliferative/quiescent cells, however it is often unclear what their molecular target is that provides this selectivity. Without this rationale, it has been hard to make progress in identifying new senolytics.

Through combined deep learning and genome-wide screening, Dr. Peterson has identified chemical features present in several FDA-approved drugs that provide this long-sought-after rationale. Considering that pathogens render healthy cells senescent, this approach has the potential to “kill two birds with one stone” in thwarting both pathogens and senescent cells.

Aims, Hypothesis & Results

The objective of the project is to conduct a series of in vitro and in vivo experiments to design new drugs that perform against a wide range of senescence inducers. Moreover, there is a clear path to iterate on the chemistry to:

1. Increase drug potency several-fold

2. Eliminate the original use of the drug (i.e. reducing unwanted effects) without affecting its anti-pathogen or senolytic activity

3. Increase the list of patentable compounds from 5 to 100s, providing plentiful patenting opportunities.

4. Use structure / function relationships to design novel scaffolds and compounds with senolytic effects.


Timeline

Pre-Clinical Studies 1: IP generation - In vitro screening
Required Funding: $110,000
Status: Planned
Duration: 6 Months

Novel compositions of matter that will be the basis of the IP-NFT will be tested in multiple cell types using multiple senescence inducers, both pathogen and more classic (DNA damage). These experiments will tell us how broadly vs. context-dependent our drug candidates are. The primary readout will be the well-accepted senescence measures.

Pre-Clinical Studies 2: IP validation - In vivo validation
Required Funding: $121,000
Status: Planned
Duration: 6 Months

Lead compounds will be tested using a mouse model. The mouse model is commonly used in the senescence field and is a well-accepted experimental paradigm. In addition to lifespan, behavioral and neurological scoring (e.g., paralysis), as well as blood and CSF biomarkers, will be assessed.

VitaDAO Board Evaluation Writeup

Senescence plays an important role in the aging process, thus targeting this is a viable therapeutic strategy. The approach targets both pathogens and aging, providing a link between the two that is currently understudied. 

The project team has strong credentials, led by Dr. Tim Peterson, an MIT- and Harvard-trained faculty member at Washington University in St. Louis (WashU), who has published numerous aging-related papers in top-tiered journals including Nature, Science, and Cell. Dr. Ron Dolle, also a WashU faculty member, is a medicinal chemist who will handle hit/lead optimizations, whose accomplishments include the advancement of more than a dozen drug candidates into preclinical and clinical studies including at least 7 investigational new drug (IND) applications.

Early data using existing drugs demonstrates that the mechanism of action (MOA) works as expected, which supports further research to determine if in vitro data will be reproducible in vivo. As these are novel compounds, the PKPD safety profiles are unknown, however this project has the potential to produce 100s of novel compounds to test. These new compounds will provide opportunities for IP-NFT value creation and the IP strategy is extensively mapped out. Therefore, the applicants will be able to begin drafting the provisional patent application promptly upon funding. Intellectual property will focus on novel compositions of matter as that will be the most valuable to future investors.

Latest Project Updates
No items found.
10
May
2022
Project Initiated!

Discover more projects & initiatives

Korolchuk Lab
Korolchuck lab proposes a drug discovery programme with the aim of identifying novel bioactive autophagy inducers. Activation of autophagy is considered a promising therapeutic approach to combat ageing and age-related diseases.
Repair Biotechnologies
Repair Biotechnologies is a preclinical-stage biotech company developing a first-in-class universal cell therapy for atherosclerosis. It aims to reduce the risk of cardiovascular events, such as heart attack and stroke.

About VitaDAO

Who can apply?
What types of projects do you fund?
What is the application structure?
Who owns IP from funded projects?
What project stages do you fund?