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.

CDC Health Advisory Warning Against Using Ivermectin for COVID-19

I’ve seen a few warnings including the CDC Health Advisory issued August 26, 2021, against using Ivermectin in COVID-19. Ivermectin is a prescription drug used to treat parasitic infections in farm animals and humans. There’s no credible evidence supporting the use of Ivermectin to treat COVID-19 in humans and its use is currently restricted to research trials.

There have been calls to poison control centers across the country from people who suffer side effects, which can include nausea and vomiting, seizures, confusion, hallucinations and more from ingesting animal grade Ivermectin. It can cause death. Certain politicians and doctors are recommending and prescribing it for humans. At least one person has been hospitalized for treatment of side effects.

I saw the FDA warning tweet quote: “You are not a horse; you are not a cow; Seriously y’all. Stop it.” I’m not sure if that was from an FDA official, mostly because I doubt that the word “y’all” would be standard usage for FDA announcements. In any case, the FDA strongly advises against using Ivermectin to either prevent or treat COVID-19.

Merck, the manufacturer of the agent, warns against it as well.

Most of the headlines I’d seen until today were connected to Mississippi and Texas. This morning, I saw a story revealing that Iowans are also buying Ivermectin in animal supply stores, probably to self-treat or prevent COVID-19. One customer claimed it was safe for humans, purchased the product and left the store.

Nobody’s going to tackle a customer who insists on using Ivermectin in a misguided effort to treat COVID-19. There’s no law against it, so nobody’s going to call the police to intervene.

There’s a song titled “Iowa Stubborn” from the Music Man, a show starring Meredith Willson, who was from Iowa. I’m hoping the “chip-on-the-shoulder attitude” will eventually lead Iowans toward making the common-sense, community minded decisions (for which we are also known) that will eventually free us from the grip of the pandemic.

In times like these, I wonder—what would Chet Randolph think?