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Utah Business

Halia Therapeutics wants to help fight Alzheimer's by harnessing a structure-based drug design strategy to discover a series of small molecule therapeutics.

Here’s how Halia Therapeutics aims to curb Alzheimer’s—and more

For Utah Business, I’ve covered biotechnology breakthroughs ranging from breast cancer diagnosis to novel intestinal disease therapeutics. But we haven’t yet discussed a disease that is even more prevalent than those combined: Alzheimer’s. 

Currently plaguing more than 6 million Americans over the age of 65, Alzheimer’s disease is expected to rise in prevalence by over 100 percent by 2050, reaching around 13 million patients within the United States alone. The US healthcare system currently spends upward of $321 billion on this disease, and those costs are only expected to skyrocket as time passes. As a result, hundreds of millions of research dollars have been allocated to groups worldwide to investigate potential therapeutic targets to disrupt the progression of this insidious pathology. 

One of these groups is the Salt Lake City-based biotechnology company Halia Therapeutics. This company has harnessed a structure-based drug design strategy to discover a series of small molecule therapeutics targeting essential mediators of inflammation. 

One of the drug targets Halia has identified is the NLRP3 inflammasome, an important mediator of inflammation in human pathologies such as cancer and neurodegenerative diseases. By targeting this inflammasome complex, Halia has reported promising data showing the prevention of NLRP3 inflammasome formation and promotion of its disassembly once formed, thereby inhibiting the production and release of proinflammatory cytokines (messenger molecules) IL-1β and IL-18. 

“The NLRP3 inhibitor has the true potential to aid patients who have Alzheimer’s disease and other neurodegenerative diseases tight with inflammation,” says Halia Senior Scientist Josue Gonzalez. “In the last couple of years, research has indicated that the immune system plays an essential role in developing these complex diseases. Like many other neurodegenerative disorders, we learned that Alzheimer’s disease starts manifesting in the mid-40s and early 50s; however, clinical diagnosis is given around the mid-60s. When the disease is not exhibiting, the immune system works at maximum capacity to maintain homeostasis in the brain environment.” 

Over time, Gonzalez says, this system starts to fail and sends incorrect signals that favor the development of the disease. “Our drug, the NLRP3 inhibitor, seeks to regulate this immune system—specifically a pro-inflammatory chemokine named IL1-beta—which is responsible for highlighting where the immune system needs to be active,” he continues. “Research shows that too much of this chemokine favors disease development, and too little of it can cause autoimmunity. Hence, it is essential to keep this chemokine in perfect balance.”

As the NLRP3 inflammasome pathway is responsible for creating the IL1-beta chemokine, Gonzalez says, Halia’s drug targets the NLRP3 inflammasome so they can determine how, when, and where the NLPR3 inflammasome is active—thus regulating NLRP3 to maintain the perfect balance of IL1-beta. 

John “Keoni” S. K. Kauwe III, co-founder and Scientific Advisory Board chair of Halia, has helped pave the way toward this brighter future for the millions of individuals living with Alzheimer’s disease—not to mention the millions of caregivers providing support to these affected millions. “I have been studying Alzheimer’s disease for nearly two decades. My work has uncovered many of the genes that impact disease risk,” he says. “Those genes make it clear that an approach based on inflammation is going to be necessary for real prevention and cure. I wanted to work in this field to use that knowledge to address the problem from unique perspectives.”

While the excitement of this therapeutic approach has been built around the Alzheimer’s disease market, targeting this inflammasome may open the door to many potential therapeutic options for numerous diseases governed by inflammation in the body. 

“When we discovered that we could disrupt the inflammasome assembly process and could vastly improve the lives of patients with many chronic diseases such as rheumatoid arthritis, inflammatory bowel disease [IBD], and macular degeneration, I realized this was the drug discovery path I wanted to follow,” says Halia co-founder and COO Jared Bearss.

Kauwe corroborates these feelings of enthusiasm regarding the potential for this targeted therapy. “All of Halia is exciting to me because it has a chance to translate my science into treatments that matter for people,” he says. “In particular, our method of targeting the NLRP3 inflammasome is exciting because it’s so different from others and has a potential impact on not just Alzheimer’s disease but many diseases tied to inflammation.”

Of course, the question will remain as to what extent this therapeutic approach may be able to lessen the burden, or even reverse, the course of Alzheimer’s disease and other destructive inflammatory disorders of the body. A major motivator to Bearss and his colleagues is the critical condition these patients find themselves in as they attempt to cope with the devastating effects of the progressive disease. Without an effective curative therapy on the market currently, the Halia team has their work cut out for them to impact the world of neurodegenerative and inflammatory disorders. 

“We are scientists committed to making a difference in the lives of people suffering from serious diseases,” Bearrs says. “I get very excited when I see that we have a way of helping improve the lives of real people. When we’re young or injured, inflammation is a helpful response. But as we age and our body’s inflammatory response has gone beyond its helpful scope, quality of life suffers. Freeing people from life-limiting, chronic inflammation is going to be transformative.”

Jeremie is an experienced MedTech and healthcare consultant, research scientist, entrepreneur, and clinician-in-training. He is passionate about identifying clinical shortcomings and developing patient-centered solutions through novel therapeutic approaches, healthcare delivery optimization, and translational research innovation.