Approved Research

Understanding the translatability of therapeutic targets identified in natural animal models of disease resistance

Lay summary

Fauna Bio is a therapeutics company creating therapies for human diseases like heart attack, fibrosis, obesity, and Alzheimer's disease. Our approach involves identifying genes in animals who are naturally able to prevent or reverse diseases. For example, small hibernating mammals get the equivalent of 25 heart attacks per year as they leave and enter a state of torpor (drastically lowered metabolic rate), yet they are only minimally damaged and are able to repair any damage without fibrosis. They also gain dramatic amounts of weight in the autumn and become insulin resistant, yet are insulin sensitive again when they emerge in the spring without suffering impacts on their health. Additionally, entering a state of torpor causes their brains to resemble that of an Alzheimer's patient with tangled proteins and lost neuron connections, yet they are able to repair their connections and clear protein tangles upon emerging from torpor.

Monitoring which genes turn on and off at the specific time points when hibernators are protected led us to identify multiple genes that could be targeted to potentially protect humans from heart attack damage and fibrosis. We have successfully targeted several of these genes in rats, and they dramatically improve heart function after a surgically simulated heart attack. We are also currently working to test targets for fibrosis, obesity, and neurodegenerative disease.

This project will have a duration of approximately three years. During this time we will not only analyze the human disease relevance of each of the genes, but we will also perform additional validation steps in the lab and in various animal models.

It will be critically important to examine mutations in the human equivalent of each of the identified genes to better understand if the potential therapies identified in hibernators will successfully translate to humans. The UK Biobank data will allow us to not only help validate the appropriateness of each gene for treating human disease, but it will also allow us to better understand if there may be potential negative health impacts that could result from interfering with each gene's effects.