Korolchuk Lab
Featured Project

Korolchuk Lab

Autophagy
Neurodegeneration
Ageing
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.
Licensing OutreachView on Molecule
Investment
$ 285,000
Initiated
14.12.2021
Approval
100% Voted Yes
Project Details
Viktor Korolchuk
Research Lead and Cell Biology
Jóhannes Reynisson
Drug Discovery
Konstantin Volcho
Organic and Medicinal Chemistry
AT A GLANCE
Stage
Early stage preclinical discovery
Area
Drug discovery
Status
Ongoing
Patent
Not filed yet

Background

Ageing is associated with the decline in the capacity of the autophagy pathway to degrade dysfunctional and damaging cellular components, such as protein aggregates and mitochondria. Dysfunctional autophagy, in turn, undermines other cellular functions including DNA repair, metabolism and survival. Therefore, activation of autophagy is considered a promising therapeutic approach to combat ageing and age-related diseases. 

Aims, Hypothesis & Results

Lysosomal dysfunction is an important factor contributing to the reduction of autophagy during aging. As dysfunctional lysosomes interfere with autophagy at the terminal stage, stimulation of autophagy initiation can be ineffective to rescue autophagy. Additionally, current methods to measure autophagy are rather unreliable, slow, and with complicated readouts, making the screening of compounds that promote autophagy less efficient. To model lysosomal dysfunction, Prof. Korolchuk lab uses cells with a mutation in a lysosomal protein (Npc1) associated with neurodegenerative diseases. When these cells are subjected to metabolic stress, they suffer cell death due to dysfunctional autophagy, providing an easy readout for an autophagy assay (cells dead/cells alive). To identify true autophagy activators, Prof. Korolchuk lab uses cells that lack initiation of autophagy and are therefore not rescuable by autophagy inducers in parallel with Npc1 KO cells.

Korolchuck lab proposes to initiate a drug discovery programme with the aim of identifying novel bioactive autophagy inducers.

Timeline

Pre-Clinical Studies 1: Identification of Lead Compounds
Required Funding: $85,000
Status: Ongoing
Duration: 12 Months
Pre-Clinical Studies 2: Synthesis and Testing
Required Funding: $20,000
Status: Planned
Duration: 2 Months
Pre-Clinical Studies 3: Future Work Upon Lead Identification
Required Funding: $30,000
Status: Planned
Duration: 6 Months

VitaDAO Board Evaluation Writeup

All of the VitaDAO evaluators considered this project worthy of funding. The assay has an easy readout, decent throughput, good controls and targeting one of the most important processes in cellular aging (autophagy). Proof-of-principle was already in place as Korolchuk Lab had previously identified hits with this approach by screening an FDA-approved compound library. The screening platform would also allow collaboration with other projects targeting autophagy/mitophagy and has potential for generation of IP/NFT for compounds. Risks to consider are the necessity for the screen to provide hits and that the specific knockout model they are using translates to having general relevance in ageing. However, the team is working on addressing the latter risk, with promising data suggesting this might not be a problem.

Latest Project Updates
No items found.
14
December
2021
Project Initiated!

Discover more projects & initiatives

Discovery of novel mitophagy activators for Alzheimer’s disease
Mitophagy - the mechanism to recycle mitochondria - becomes dysregulated with age and is thought to be a driver of Alzheimer’s and other age-related diseases. The Fang lab aims to use a combination of artificial intelligence and a wet-lab validation platform to identify new mitophagy-activating drug candidates.
Scheibye-Knudsen Lab
What if therapeutics to slow down the aging process and prevent age-related disease already existed? The Scheibye-Knudsen Lab will use advanced machine learning to crunch the data from 1.04 billion prescriptions to understand the impact of drugs on human lifespan.

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?