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0/ The search for COVID-19 therapies should revolve around a single question that’s staring us right in the face, and we’re mostly ignoring it:
1/ Why are COVID-19 outcomes *dramatically* skewed against older adults?
It’s less risky to get COVID-19 while suffering from obesity, cardiac issues, diabetes, or one of many other comorbidities than it is to do so while just existing as an older adult. https://medium.com/spring-discovery/covid-19-is-the-latest-disease-to-point-at-our-need-to-treat-immune-aging-a35e94e01ba8
It’s less risky to get COVID-19 while suffering from obesity, cardiac issues, diabetes, or one of many other comorbidities than it is to do so while just existing as an older adult. https://medium.com/spring-discovery/covid-19-is-the-latest-disease-to-point-at-our-need-to-treat-immune-aging-a35e94e01ba8
2/ We know we should be protecting older adults from infection.
But how can we use the connection between COVID-19 and aging to better find therapies?
How do we find drugs that get at a root risk behind COVID-19's devastation to the elderly: the aging of our immune systems?
But how can we use the connection between COVID-19 and aging to better find therapies?
How do we find drugs that get at a root risk behind COVID-19's devastation to the elderly: the aging of our immune systems?
3/ Spring Discovery has been building this for years: a team + tools laser-focused on therapies for aging.
We recently pointed our tech at understanding how our immune systems respond to viruses differently as we get older, and we want to share some results:
We recently pointed our tech at understanding how our immune systems respond to viruses differently as we get older, and we want to share some results:
4/ Others working on COVID-19 therapies are focused on (1) antivirals that target the virus itself, (2) drugs that tweak the immune response, and (3) antibody treatments.
All this should happen and more, but something is missing...
All this should happen and more, but something is missing...
5/ We need therapies that target age-related immune decline itself.
This means starting with a different question: Why does an older adult’s immune system fare so much worse than a younger person’s? And which drugs might help?
This means starting with a different question: Why does an older adult’s immune system fare so much worse than a younger person’s? And which drugs might help?
6/ New tools are needed to answer that. The immune system is notoriously complex, and many brilliant minds are trying to profile it.
Spring measures immune aging by arming our scientists with the tools of machine learning + lab automation to measure many complex phenotypes…
Spring measures immune aging by arming our scientists with the tools of machine learning + lab automation to measure many complex phenotypes…
7/ We've built tools that measure immune cell-to-cell interaction, organelle structure, cytokine levels, morphology, and other hidden complexities that contribute to age-related dysfunction.
All within a single well
All within a single well
8/ Our team + our tools form a machine that shows promise for profiling the aging immune system and screening compounds to rejuvenate it.
Dive into today’s preprint or read on. https://www.biorxiv.org/content/10.1101/2020.07.30.223875v1
We screened thousands of drugs...
Dive into today’s preprint or read on. https://www.biorxiv.org/content/10.1101/2020.07.30.223875v1
We screened thousands of drugs...
9/ …and we’re using this preprint to highlight one drug in particular surfaced by our machine that we believe deserves investment as a candidate for COVID-19: disulfiram.
It’s got a lot of properties you’d want in a pandemic: approved/generic/cheap/promising safety profile…
It’s got a lot of properties you’d want in a pandemic: approved/generic/cheap/promising safety profile…
10/ Identified via unbiased screening of thousands of drugs and multiple dose responses in our platform, disulfiram shows promise for restoring age-related phenotypes: cytokine levels, t-cell phenotypes, viral infection phenotypes, more.
(In vitro, needs followup, see preprint)
(In vitro, needs followup, see preprint)
11/ Disulfiram was identified by leading immunologists Judy Lieberman and @WuLabHarvard and highlighted by @VirusesImmunity as having specific anti-inflammatory properties...
12/ ...including an ability to inhibit inflammasome-mediated pyroptotic cell death ( https://www.nature.com/articles/s41590-020-0669-6).
These mechanisms may have direct relevance to root causes of COVID-19’s runaway inflammatory processes.
These mechanisms may have direct relevance to root causes of COVID-19’s runaway inflammatory processes.
13/ And excitingly, a couple days ago UCSF announced a small proof-of-concept trial testing disulfiram in COVID-19 patients.
We hope this is the first of many steps taken to explore a drug we think holds promise for different reasons than the majority of COVID therapies...
We hope this is the first of many steps taken to explore a drug we think holds promise for different reasons than the majority of COVID therapies...
14/ ...A drug we surfaced by asking the question,
“How do we help an older adult’s immune system respond to a virus like a younger person’s?”
“How do we help an older adult’s immune system respond to a virus like a younger person’s?”
15/ The implications of tech that can help search for therapies for immune aging are wide-reaching, far beyond COVID-19.
We need new tools capable of doing so in a high-throughput, systematic manner. This is our mission @springdiscovery — read more: https://medium.com/spring-discovery/covid-19-is-the-latest-disease-to-point-at-our-need-to-treat-immune-aging-a35e94e01ba8
We need new tools capable of doing so in a high-throughput, systematic manner. This is our mission @springdiscovery — read more: https://medium.com/spring-discovery/covid-19-is-the-latest-disease-to-point-at-our-need-to-treat-immune-aging-a35e94e01ba8
16/ PS Like many in bio, it’s been HUMBLING seeing our team respond to this.
Spring's rallying cry since founding has been “Progress Every Week!” Since late Feb when we saw the promise of aging tech for COVID-19, I've witnessed nonstop heroics to honor this value.
More soon.
Spring's rallying cry since founding has been “Progress Every Week!” Since late Feb when we saw the promise of aging tech for COVID-19, I've witnessed nonstop heroics to honor this value.
More soon.
17/ We're deeply grateful for early belief, support, and collaboration w/ many experts:
Ralf Schwander's incredible group at AssayWorks, @george_kuchel / Laura Haynes / UConn team, Jorg Goronzy, Tamas Fulop, Diane Heiser, Anis Larbi, and more
Ralf Schwander's incredible group at AssayWorks, @george_kuchel / Laura Haynes / UConn team, Jorg Goronzy, Tamas Fulop, Diane Heiser, Anis Larbi, and more
