How Animals Are Inspiring Potentially Life-Saving Human Medicines
Bats have been maligned throughout human history. For centuries, our ancestors believed they carried sinister powers, while in the past three decades we have discovered that they can host hundreds of deadly viruses, from Ebola to coronaviruses to rabies.
But this very feature of bats is part of why they are so important to study. Honed over more than 65 million years of evolution, their unique immune systems can tolerate viral loads that would kill many other mammals. While humans respond to viruses by ramping up immune defense mechanisms, sometimes initiating an inflammatory cytokine storm which can harm our own organs, bats take the opposite approach. Their physiology is specifically designed to counteract any inflammation resulting from the presence of a pathogen, allowing them to peacefully co-exist with any number of viruses.
This ability has likely arisen for a variety of reasons. Many bat species live in extremely high-density colonies with hundreds of thousands of individuals co-existing on a single cave ceiling or tree, promoting rapid viral transmission. Also, as the only flying mammals, bats must deal with the enormous stresses that flight exerts on their cells, from rapid increases in body temperature to damage to their DNA. Tamping down inflammation is thought to be a crucial coping mechanism.
The extreme biology of bats has prompted the formation of a biotech startup that views these intriguing animals as a potential unlock for new human medicines. At the end of 2021, the biologists Paul Matsudaira, Richard Young and Thomas Zwaka, formed Paratus Sciences with the idea of improving our understanding of bat biology to aid the development of novel human therapeutics. (Leaps co-led a Series A investment in Paratus to accelerate their efforts to develop a new class of anti-inflammatory drugs.)
Last year, a paper published in Cell by the company’s academic collaborators in Singapore, highlighted one particularly promising drug target, a protein called ASC2 which appears to play a major role in the creatures’ ability to regulate inflammation.
Theresa Heah, CEO of Paratus Sciences, explains that much of the research work involves sequencing bat genomes and comparing them with human DNA, to identify relevant targets which might be applicable to our own biology. Zwaka and other scientists from the Icahn School of Medicine at Mount Sinai have also managed to extract cells from bat tissue and convert them into pluripotent stem cells, which can be studied to understand the many genes and proteins involved in their immune response.
“We’re still in the early stages,” says Heah. “Our initial focus is on inflammation. We’re taking all the information we can gather from cell studies and genome sequencing, and it goes through high throughput screening, using machine learning to create potential drug targets. We’re hoping to move towards preclinical studies in vivo to validate those targets.”
Paratus’s pioneering work is an example of an emerging paradigm within the field of drug discovery: Turning to other animals to help accelerate the search for the medicines of the future.
When QBiotics Group, an Australian life sciences company, began developing drug candidates for a group of rare cancers that affect the body’s connective tissues, known as soft tissue sarcomas, they turned to dogs. Just like humans, our canine friends can also develop soft tissue sarcomas underneath their skin, which can metastasize and spread with fatal consequences.
“Canine tumors share many biological, genetic, and histologic features with their human tumor counterparts,” says Dr. Victoria Gordon, Executive Director and Co-Founder at QBiotics Group. “They retain the complexities of naturally occurring drug resistance, metastasis, and tumor-host immune reactions.”
Studying soft tissue sarcomas in dogs has directly enabled QBiotics to hone the dosing and treatment regime for their lead molecule. As a result, the company has applied for Orphan Drug Designation with the Food and Drug Administration and is now recruiting for a Phase II clinical trial in soft tissue sarcoma patients, at the Memorial Sloan Kettering Cancer Center in New York.
Turning Weapons Into Medicines
While much can be gleaned from examining the similarities and differences between humans and other species, another approach is to examine the weapons that various creatures have evolved over hundreds of millions of years to attack or paralyze their prey.
Various biotechs are searching for the blockbuster drugs of the future in venoms, some of the most potent chemicals on the planet. The very nature of venom means that it combines both speed of action with precise delivery to a particular target, and some companies have already discovered various active compounds within these poisonous cocktails that are now being synthesized and repurposed for medical uses. To cite just one example, Dublin-based Celtic Biotech is developing a novel cancer therapeutic based on a toxin found in rattlesnake venom that causes cancer cells to self-destruct.
Many of these drug candidates are often discovered by happenstance. Back in the mid 1990s and early 2000s, Edmond Godfroid, co-founder and managing director of Belgian biotech Bioxodes, was searching for a better way of detecting Borrelia Burgdorferi, the bacteria that causes Lyme disease, in the blood of patients bitten by infected ticks. As part of this research, he began studying the molecules present in tick saliva and how they interact with our own bodies to enable the insects to feed.
Godfroid discovered that tick saliva contains not only an anaesthetic, which allows it to bite into the host without being disturbed, but also powerful anticoagulants. “To feed, it’s very important for the ticks to maintain the fluidity of the blood and to block the coagulation processes developed by the host,” he says. “That’s why ticks have evolved to secrete many different compounds targeting all these coagulation processes across humans, reptiles, birds, and others. It’s an amazing adaption, which has enabled them to feed on many different species.”
He soon realized that these anticoagulants could have a range of uses, particularly in patients who have suffered brain hemorrhages, where the formation of small blood clots within minutes to hours is a significant cause of secondary brain injury and potentially preventable deaths. As a result, Bioxodes is now using a protein called Ir-CPI, which is based on an anticoagulant found in tick saliva, as the active component in their drug candidate that is in phase 2 clinical studies.
Understanding animal biology could ultimately lead to more than one drug. Bioxodes is also hoping to develop drug candidates from molecules found in tick saliva that could prevent clotting during cardiac surgery. And Paratus Sciences is intrigued by the low cancer rates among certain bat species, with a recent study in Nature attributing this to the downregulation of three genes.
Future research could potentially lead to drugs that improve cancer resistance in humans. Bats may even hold secrets that could push the boundaries of human lifespans. The majority of bat species live more than three times longer than other small mammals, with the big brown bat living for nearly 20 years in the wild, while one bat in Siberia was even found to have lived to 41. In contrast, similar-sized animals like house mice tend to live for just two years.
“Bats have developed these remarkable physiological traits that may very well hold the key to transforming human health,” says Paratus CEO Heah. “And they do this while living in habitats that are similar to ours. So there’s a lot to be learned here, and they can help teach us some things about human biology which we haven’t been able to characterize in the past.”
Special thanks to David Cox for his additional research and reporting for this article.
The article was initially published on Forbes.com on February 22nd, 2024
