U.S. company Holoclara is looking to tackle diseases through the development of worm-derived therapeutics.
Allergic and autoimmune diseases were first described in the early 1900s, which Holoclara said is the same time that gut-resident worms such as the roundworm, Caenorhabditis elegans, were removed from people in industrialized countries.
The company, led by CEO Andrea Choe, said there is a connection. Areas of the world that continue to have a high incidence of gut worm infestation are largely free of allergic and autoimmune diseases. It is believed that these worms produce molecules that limit inflammation and promote tissue repair.
Also, worms have been used to treat immune diseases and efforts have been made, without success, to identify worm-derived therapeutic compounds. Holoclara has a discovery engine designed to isolate and identify molecules from the 1mm-long roundworms to help the millions of people suffering from allergic and autoimmune diseases.
On this week’s podcast, we had a conversation with Choe about her work and the company.
“These diseases… could have happened because we removed gut roundworms.”
What’s so special about roundworms?
The activities of the worms were of special interest to Choe.
“They would go left, they would go right, they would mate, they would aggregate. What is mediating these behaviors? I just really wanted to take on this project of understanding what it was that worms were secreting, that they’re using to communicate with each other. They were using the same molecular language; there’s a predator over here, or there’s food scarcity over here, there’s potential mates over here,” Choe said.
“The truth is, we’re supposed to have worms. If you look at mummies, they had worms. Homo erectus before Homo sapiens, they had gut roundworm. So did King Richard III.”
So, what changed?
“At the turn of the century, something happened,” Choe explained.
“There was suddenly this increase in allergic and autoimmune disease. Is it a coincidence? I don’t know, but there was this sort of hypothesis that these diseases that started arising could have happened because we removed these gut roundworms.”
Choe noted that the solution isn’t to simply ingest roundworms.
“If you look at what the FDA is doing, of course they’re not going to want you to take a living parasitic worm. So, they just want you to find what is it that they’re secreting that could be responsible for this. So that’s when we thought, okay, we have discovered this molecular language from roundworms. There’s got to be something in there that can be responsible for this. And that’s what we found. Some of the molecules that we studied were incredibly therapeutic. They could block clinical models of allergic disease, autoimmune disease, and it was pretty remarkable.”
Roundworms – adapting to their environment
Choe explained that the worms’ goal is simply to protect themselves by secreting compounds that block our inflammatory response to that worm.
“For example, eosinophilic diseases. The eosinophil is actually designed to get rid of parasitic worms. So, could it be that people with eosinophilic diseases, actually their body thinks that there’s a worm there when there isn’t, and so it’s starting to attack its own body? And could it be that these molecules that we found that the worms are using to temper that response could help them?” Choe said.
“We’d like to return key secretions from gut roundworms that are intended to be a part of our ecosystem and can potentially make a huge impact on human health.”
The treatment Holoclara is developing will be a pill taken orally. Initially, the company will be looking to develop worm derived therapeutics related to allergic diseases.
Choe said clinical trials will begin in 2024.
To learn more about this topic:
Here are some links to more articles on the subject of worms, allergies, and autoimmune diseases.
7 Autoimmune Diseases Biotechs are Fighting to Treat (Labiotech.eu)
Therapeutic worms for inflammatory disorders (University of Edinburgh)
How re-engineering antibodies can prevent allergies (Labiotech.eu)