Welcome to Issue 3 of The BIG Brief — a periodic digest of what is top of mind at Project BIG.
Our mission is to unlock the cause and cure for MS and other neurological and autoimmune diseases through a unique clinician-scientist collaboration across disciplines. Our team of scientists, researchers, neurologists, immunologists, radiologists, microbiologists, psychologists, and patient advocates at Stanford are engaged in some of the most high-impact and exciting Brain-Immune-Gut (BIG) research taking place anywhere. The BIG Brief provides a snapshot of their worlds as well as a curated collection of articles that have captured our team's attention.
Spotlighted: Lily Sarafan, Project BIG Founding Partner
We are thrilled to announce that Project BIG founding partner Lily Sarafan has been elected to the Stanford University Board of Trustees. Lily has a long track record of committed service to her alma mater Stanford, where Project BIG is headquartered. Congratulations, Lily!
What excites you the most about Project BIG?
We're uniquely positioned to have an extraordinary scale of impact. Our initial target of multiple sclerosis is among the most complex diseases ever studied, so discovering answers here could unlock a deeper understanding of the central nervous system, the brain, and the microbiome, among other systems. The broader applications of the research to autoimmune and neurodegenerative diseases mean that BIG research discoveries can positively impact the tens of millions of Americans and many more around the world who live with these chronic conditions. Add to that the world-class team Project BIG has assembled and the culture of purposeful research and interdisciplinary collaboration Stanford is known for and we have a recipe for impact that's nothing short of exciting.
What broader brain, immunology, or gut research are you most interested in right now?
Transcending intellectual interest, I'm truly inspired by the relatively new discovery of the lymphatic system of the brain. It's hard to believe that there existed an entire body part, and a critical one, that we only learned of in 2015 when so much of our anatomy has already been mapped. Imagine the possibilities – there are still many unsolved mysteries of the human brain. The discovery of the meningeal lymphatic system highlights a specific connection between the brain and the immune system that was previously thought to be nonexistent and represents a dogmatic shift in our understanding of how these systems communicate with one another. The specific implications of this finding are vast and unresolved, but we now believe this lymphatic system factors into diseases where immune dysfunction harms the brain, including MS and Alzheimer’s.
What is the facet of personal health that you're most committed to?
I get a full night's sleep almost every night. There is an unhealthy badge of honor associated with getting by with little sleep. While there are outliers who can do so without harm, the vast majority of us need several hours of uninterrupted rest to function at optimal levels on a day to day basis and to improve our long term health outcomes. This TED talk by Matt Walker provides a powerful and memorable synopsis of what we know to date about the critical role of sleep. In Project BIG terms, our brain, immune system, and gut all rely on a healthy dose of shut-eye.
BOOKMARKED: MS NEWS
Treating MS during the COVID-19 Pandemic. People living with MS and their treating physicians are faced with important decisions during the COVID-19 pandemic. This commentary highlights the unique considerations of initiating, ceasing, and continuing treatments for MS and implications for service delivery. Teletherapy for some appointments and decreased frequency of dosing of infusion therapies are discussed among other strategies. While some therapies may increase the risk for more severe symptoms and may impact the efficacy of future vaccines, people with MS should undertake changes to their treatment only in discussion with their neurologist.
Digital triage to reduce unnecessary hospital visits. One of the impacts of COVID-19 has been an increased urgency to develop useful digital tools to improve diagnosis and treatment and reduce unnecessary health care visits for people with MS. This digital triage tool is especially compelling in that in addition to reducing unnecessary exposure risk via hospitals or outpatient clinics, it may reduce health disparities for people living far away from treatment centers.
Funding to study a new diagnostic biomarker in MS. The Cleveland clinic received a 7.2-million-dollar grant from the NIH to study the potential for the central vein sign (CVS) to serve as a new diagnostic biomarker for MS. Given the difficulty in obtaining an accurate MS diagnosis (up to 20% of MS diagnoses can be inaccurate), identifying the MRI-based CVS as a superior diagnostic biomarker would allow earlier accurate diagnosis of MS and enhance clinical decision-making.
Bedside to Bench in MS. In this brief commentary, the movement from clinical observations (bedside) to scientific discovery (bench) in MS is discussed. In line with the ethos espoused by Project BIG, the critical role of the clinically active physician-scientist in identifying, via direct patient observation, phenomena that are then translated into clinical trials and scientific progress in MS is highlighted.
Why don’t we have a vaccine against autoimmune diseases? A review discusses the considerations for developing a vaccine for autoimmune diseases, such as MS and rheumatoid arthritis. Factors contributing to the challenge of developing such a vaccine are highlighted. For example, the fact that unlike vaccines for infectious diseases, which are generally preventive and designed for immune-naïve people, vaccines for autoimmune diseases would be therapeutic and developed for people with an existing inflammatory immune response. Because there may be different mechanisms driving the disease for different people, identifying the target for an autoimmune vaccine has proven complex.
BROADER BIG (BRAIN-IMMUNE-GUT AXIS)
COVID-19 and the gut. Recent attention has turned to the impacts of COVID-19 on the gut. From a case report in China identifying digestive problems as the first symptoms of COVID-19 in a small sample of children to a Stanford study finding that hospitalization among patients was 8 times more likely in people experiencing diarrhea as a symptom, recent research is pointing to an important relationship between the gut and this novel virus. ACE2 receptors, found in high numbers in the GI tract, are thought to at least partially explain the GI symptoms associated with the virus.
The zeitgeist of hand hygiene. In this anthropological examination of hand washing, the tension between avoiding contagion during a pandemic and concerns about antibiotic resistance is discussed. The hygiene hypothesis and disagreements about the utility of hand sanitizer are not new, however the potential for this pandemic to fundamentally change how humans view hand washing and hygiene in general is.
Why COVID-19 hits some harder than others. Many of the questions posed in this April article about why some people experience more severe symptoms than others remain relevant. The authors discuss the impacts of health disparities on the immune system and the ways that, “The immune system is a function of the communities that brought us up and the environments with which we interact every day.”
[Listen] Menopause and the brain. In this 13-minute TED talk, neuroscientist Lisa Mosconi discusses her cutting-edge research on the relationship between falling hormone levels in menopause and brain aging.
IMPACTED
"Being able to manage expectations of what I could or could not do while receiving treatment would have allowed me to more effectively plan the life adjustments needed, including taking leave from work and arranging lifts to my treatments. It would have helped me feel more in control of my life and empowered about my care." A chemotherapy recipient espouses the importance of informing patients of the cognitive and psychological impacts of treatments and discussing concerns about symptoms before, during, and after treatments.
QUOTED
“If science were explained to the average person in a way that is accessible and exciting, there would be no room for pseudoscience.” – Carl Sagan
COMMITTED
We are committed to high impact research that seeks to unlock the brain-immune-gut axis and positively impact millions of lives. We do this by leveraging the world-class human capital, interdisciplinary ethos, and culture of translational medicine that Stanford is recognized for. We are grateful for the support from our generous community donors and hope to continue building on this momentum to achieve BIG results. If you know of an individual or foundation that may choose to support this work, please let us know.
Do you have an article or content that you would like to see in the next BIG Brief? Send an email to editor@projectbig.com. Questions? Contact us or visit our FAQs.
Live well,
Shadi Gholizadeh, PhD, MPH & The BIG Brief Editorial Team
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