Exploiting Natural Disease Resistance in Mammals To Advance Drug Development
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In order to develop new therapeutics, natural disease resistance in humans can be used. However, this endeavor remains a challenge as there are not sufficient numbers of humans resistant to enough conditions. Researchers are therefore exploring alternative strategies in efforts to develop novel therapeutics. As humans share 90% of their DNA with mammals, natural disease resistance across all mammals could be used as one such strategy.
We spoke to Ashley Zehnder, CEO and founder of Fauna Bio to learn more about how the company seeks to find new treatments for diseases such as cancer and Alzheimer’s, by exploiting natural disease resistance in mammals.
Kate Robinson (KR): How can natural disease resistance in mammals be exploited to develop therapeutics?
Ashley Zehnder (AZ): Recent therapeutic developments show that disease resistance is a powerful path to new treatments (take the development of PCSK9 inhibitors for high cholesterol as an example). At Fauna, we recognize that as humans, we have the genes to heal ourselves and resist disease, but many are dormant. However, we’ve now discovered how to reactivate those genes by studying animals that have adapted to survive some of the most extreme environmental conditions on the planet. As part of this, they have evolved ways to combat conditions like Alzheimer’s disease, reverse damage from diseases like heart attack and stroke and prevent muscle and bone loss.
We share around 92% of our genes with other mammals (e.g., rodents), this means we can use the discoveries from these species to create new treatments for humans.
KR: Are there any key considerations or challenges when approaching drug development in this way?
AZ: It is always important to consider how genes are conserved or how they are changing across mammals (including humans) when using this approach. Our founding team has deep expertise in comparative genomics (the study of how genomes are alike and different across many, many species) and this gives us an advantage in gaining new insights from the data.
KR: What are the benefits to using mammalian genes in drug discovery?
AZ: Current drug discovery efforts – for conditions ranging from cancer to Alzheimer’s disease to obesity and heart disease – based on human data struggle to find new, unique and potentially more successful treatments.
A great way of finding new treatments is to look for humans with natural resistance to a disease, which is how we discovered drugs like PCSK9 inhibitors for high cholesterol. Unfortunately, finding human populations resistant to many disease states is difficult, if not impossible. We can extend the same discovery process to animals who have evolved disease resistance and find new therapies for diseases that do not currently have effective treatments. There is much broader natural diversity when you consider the full range of mammals than when you consider variation within a single species (e.g., humans) and this enhances our ability to find novel therapies.
KR: Have any techniques and/or technologies been particularly instrumental for advancing this area of research?
AZ: The number of available mammal genomes has increased 1300% in just 10 years. Much as the cost of sequencing the human genome has decreased from $2.7 Billion in 2003 to less than $1000 in 2019, the cost for assembling new mammal genomes has decreased exponentially and opens up many new species for discovery. Improved techniques for sequencing RNA and proteins have improved the quality and also reduced the cost of these types of sequencing as well, making this an unprecedented time to find new insights into how animals resist disease.
KR: Can you tell us about the possible future implications of these therapeutics in treating indications such as cancer and Alzheimer’s disease?
AZ: Millions of people die every year from cancers, respiratory diseases, stroke, Alzheimer’s disease and diabetes – and similarly to heart health, humans have dormant genes that we know are active in animals which could help offer natural protection against these conditions. By exploiting our knowledge of natural disease resistance and highly conserved genetic pathways, it is more likely that therapies will truly make an impact on human disease. Traditional drug discovery has failed in identifying solutions to many of these persistent and pervasive health challenges. Rather than simply relying on gene targets within people, which can be sparse and difficult to find, Fauna Bio takes a broad approach within the animal kingdom so we are able to identify first-in-class therapies more quickly. It is this novelty and innovation that is currently lacking in pharmaceutical pipelines – addressing a > $60 billion potential market.
Ashley Zehnder was speaking with Kate Robinson, Editorial Assistant for Technology Networks