The Path to Asapiprant: Perspiration or Inspiration?

I just found a University of Iowa Health Care announcement about a potential novel treatment to protect older patients from the ravages of Covid-19 infection. According to the announcement:

“An experimental drug that counters immune aging, effectively prevents death in older mice with severe COVID-19, suggesting it may have potential as a therapy to protect older people who are most at risk from the disease. The new findings by researchers with University of Iowa Health Care were published recently in the journal Nature.”

The experimental drug is called Asapiprant. I’m far from knowing anything much about immunology but the path to this discovery reminds me of the work of Ed Wasserman who wrote a book I’ve not yet read but probably should, As If By Design: How Creative Behaviors Really Evolve (2021, Cambridge University Press).

I first found out about Dr. Wasserman from an episode of The University of Iowa’s virtual events of Uncovering Hawkeye History. The title for this one was “Endless Innovation: An R1 Research Institution (1948–1997).” This event series was designed to highlight notable elements of UI’s 175-year history.  

Anyway, in a nutshell, Wasserman’s theory is that innovation is often more about perspiration rather than inspiration. He says it’s often a combination of the 3 C’s: Context, Consequence, and Coincidence. And while I was noodling around on the web, it struck me that this might fit how the Asapiprant innovation developed.

To be sure, the University of Iowa was a critical part of the story of how Asapiprant eventually became an important agent to protect the elderly from immune system aging and thereby decrease the mortality from Covid-19 disease.

I found out the agent was originally called S-555379. It was developed by Shionogi & Co., Ltd as a possible treatment for hay fever several years ago. I think that would be the Coincidence.

But in 2011, Stanley Perlman MD, PhD, professor of microbiology and immunology in the UI Carver College of Medicine, published a paper, which I think is part of the Context:

Zhao J, Zhao J, Legge K, Perlman S. Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. J Clin Invest. 2011 Dec;121(12):4921-30. doi: 10.1172/JCI59777. Epub 2011 Nov 21. PMID: 22105170; PMCID: PMC3226008.

This paper was cited by Shionogi in the company’s announcement of their license agreement with BioAge Labs, Inc., posted on January 26, 2021:

“It is known that age-related declines in immune function are significant risk factors that increase morbidity and mortality from infectious diseases2. Therefore, it has been suggested that restoring immune function may reduce the severity of various infectious diseases, including COVID-19. The DP1 receptor has been identified as a drug discovery target that improves age-related declines in immune function in an original AI-driven analysis of longitudinal omics data in humans conducted by BioAge. In addition, in a study conducted at the University of Iowa by Dr. Stanley Perlman in which an existing DP1 receptor antagonist was administered in an aged mouse model of SARS coronavirus (SARS-CoV) infection, the mortality rate of mice was improved and a significant decrease in viral load in the lungs was observed3. Based on these exciting study results, we have concluded a license agreement in expectation of development of this compound as an immunopotentiator for the elderly by drug repositioning.”

And I think part of the Consequence is that BioAge, Inc. has announced that the drug, the name of which was changed to BGE-175 and now called Asapiprant is about to undergo Phase 2 clinical trials for treating older patients hospitalized with COVID-19.

Whether you call it perspiration or inspiration, I think it deserves our admiration.

Featured image picture credit: Pixydotorg.

Author: James Amos

I'm a retired consult-liaison psychiatrist. I navigated the path in a phased retirement program through the hospital where I was employed. I was fully retired as of June 30, 2020. This blog chronicles my journey.

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