Notes on Engineering Health, December 2020: 2020 and Lung Inflammation

Jonathan Friedlander, PhD
Geoffrey W. Smith

Jonathan Friedlander, PhD & Geoffrey W. Smith

December 31, 2020

2020 has been the year of airway inflammation. Everyone became an immunologist in record time with a specialization in infectious disease and a fellowship in lung damage. Words like cytokine (storms) and R0 have become common lingo in households. The difficulty of understanding and treating airway inflammation, however, was no stranger to the medical community, despite lengthy efforts to better understand targeted therapies to ameliorate its effects.

The nature and development of airway inflammation in individuals may be driven by numerous factors including pathogenic infections and inhaled particulates. Pathogenic infections are one of the main reasons for acute airway inflammation. The WHO estimates that influenza annually results in between 3 and 5 million cases of severe illness and between 250,000 and 500,000 deaths worldwide. The death toll of the current epidemic is still evolving, but as of publication of this note at least 1.7 million people across the globe have died from COVID-19. Pollution and relatively innocuous inhaled particles such as allergens are also common causes of airway inflammation affecting over 300 million people suffering from asthma globally.

During any acute airway inflammation attack, an active inflammation response and an appropriately efficient resolution are equally important. Indeed, the inability to strike the fine balance between being protected and overreacting is often the engine to more serious pathologies. The failure to resolve inflammatory immune responses results in chronic inflammatory airway diseases. Chronic airway inflammation is a general feature of chronic obstructive pulmonary disease (COPD) which affects ~5% of the global population and is the fourth leading cause of death worldwide. COPD was estimated by the CDC in 2010 to cost the US more than $32 billion annually, with a projection to grow to an annual cost of $49 billion by 2020. Chronic airway inflammation is also a critical issue in certain types of asthma, cystic fibrosis (CF), and bronchopulmonary dysplasia (BPD).

Current strategies to treat these chronic pathologies focus in large part on inhibiting pro-inflammatory pathways in the lung. For example, targets for the treatment of various forms of severe asthma and allergy that are currently drugged include: IgE for allergic asthma, three different epitopes of IL-5 (here, here and here) for eosinophilic inflammation, and the receptor of IL-4 which blocks both IL-4 and IL-13 pathways. It should be noted that a number of these drugs (here and here) were candidates to help curb the immune response triggered by the COVID-19 infection, but none of them have proven to be efficacious.

Some encouraging novel efforts to treat chronic airway inflammation are targeting alternative and more recently discovered avenues such as the JAK pathway. As mentioned above, the challenge to such strategies is to effectively shut down part of the immune response without leaving the patients vulnerable to opportunistic pathogens or crippled by side effects. Due to different profiles of inflammatory responses, however, no single strategy has proven itself to be effective for all people, and response rates for existing therapies have generally been poor.

Increasing specificity without sacrificing efficacy is a difficult path to walk. To this end, Digitalis is proud to have launched Alcea Therapeutics which is focusing on controlling regulatory T cell (Treg) dysfunction during inflammation. Alcea is built on the belief that the ability to identify and target specific populations of Tregs will hold the key to greater efficacy and specificity in treating severe asthma, not by treating symptoms but by resetting a healthy balance in specific immune systems. More soon!

On this hopeful note, everyone at Digitalis wishes you a safe and healthy end to 2020 (at last) and a much happier New Year.

Jonathan Friedlander, PhD & Geoffrey W. Smith

First Five
First Five is our list of essential media for the month which spans a range of content including scientific papers, books, podcasts, and video. For our full list of interesting media in health and science, updated regularly, follow us on Twitter or Instagram.

This month a collection of four themes that appear regularly in these Notes plus a check-in with FDA:

1/ More Nutrition
As noted below in our update on the Digitalis Commons, we remain concerned with issues of diversity and inclusion in STEM domains. This recent piece in the New York Times notes that these issues extend to our study of and advice on our diets. Recent stories have also also picked up on the increasing impact of AI on our understanding of the impact of nutrition on health—in this case a detailed mapping of cancer-beating molecules in foods.

2/ More Gut Microbiome
As we noted in our November Notes, reports on the impact of the gut microbiome on health continue to pile up. This month it is a study in Nature indicating that gut microbiota that have been depleted by chronic antibiotic treatment leads to altered sleep/wake cycles.

3/ More Obesity
The incidence of obesity remain at crisis levels. Continued concerted efforts focused both on health behaviors and on the biology of weight are needed to address the crisis. At the population level, a large study details the impact of long-term obesity on health. This article points out more detailed understanding of how obesity impairs immune cell functions and can accelerate tumor growth. And this report delves into how an obesity-related gene controls cravings and exercise motivation in mice which could inspire new therapies.

4/ More Flavanols
Interesting data related to the power of dietary flavanols continues to be generated. Emerging evidence suggests that flavanol-rich diets protect against cognitive aging. This study shows for the first time that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. Another report shows that flavan-3-ol intake is associated with lower blood pressure across a large population.

5/ FDA in Action
The FDA has been busy. In addition to authorizing emergency use for the first COVID vaccines, the agency has approved two other firsts:
Genetically engineered pigs for both food and medical uses, and
An obesity therapeutic focused on genetic defects.

Digitalis Commons
Public-Interest Technologies for Better Health

Digitalis Commons is a non-profit that partners with groups and individuals striving to address complex health problems by building public-interest technology solutions that are frontier-advancing, open-access, and scalable.

New Program to Support Underrepresented Groups in STEM
It is regrettably all too clear that certain populations remain underrepresented in health-related sciences on a national basis. Underrepresentation of these groups in the field overall trickles down to their underrepresentation in the life sciences commercialization and entrepreneurship community and ultimately in the amount of money that companies led by members of these underrepresented groups receive from venture capitalists.

In December 2020, Columbia Technology Ventures, with support and sponsorship from Digitalis Commons, announced the launch of Columbia’s Program for Diversity & Inclusion in Commercialization & Entrepreneurship (DICE). The program aims to support early-career individuals who identify as being from traditionally underrepresented groups in life science entrepreneurship and commercialization as defined by the NIH. DICE will provide eligible Columbia graduate students and postdocs with educational programming, mentorship, networking, and funding opportunities to prepare participants for careers in bringing life science innovation to market.

The focus areas of the program are therapeutics, diagnostics, medical devices, and enabling technologies.

To learn more about the program, including details of the program structure, eligibility, awards & grants, and timelines, please visit techventures.columbia.edu/DICE.

For additional questions about the program, please contact techventures@columbia.edu