THE BIG BRIEF
Welcome to Issue 5 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: Recent Achievements
We wanted to share a few, among many, key achievements and updates with you, our stakeholders and supporters.
Under the leadership of Dr. Jeffrey Dunn, the first few months of 2022 have been a time of growth and major strides at Project BIG. The Brain, Immune, Gut (BIG) Research Initiative at Stanford University seeks to elucidate and advance our understanding of human autoimmune disease. The architecture of this research inverts the classic paradigm and places the clinic at the center of investigation. We anticipate this will serve to transcend historical roadblocks in the path of discovery.
In Project BIG, clinical cases are identified, consented, and annotated with advanced multimodal clinical and imaging metrics by faculty and staff of the Stanford Neuroimmunology Division. Biospecimens, including whole blood, cerebrospinal fluid, and stool, are collected, processed, and stored in partnership with the Stanford Clinical Trials Research Unit. Our clinic research team then approaches or is approached by scientific collaborators to plan and execute state-of-the-art immunologic investigations on human samples. This process brings curated human tissue to the scientist, whose discoveries are made immediately more relevant given the well-defined clinical phenotype, and novel ability to assess paired samples within an individual according to disease status, or to assess serial samples collected in longitudinal follow-up.
Here are just a few of the many exciting projects underway:
A team led by Stanford's William Robinson, MD, PhD, Tobias Lanz, MD, and Lawrence Steinman, MD recently proved that the Epstein-Barr virus (EBV) triggers MS. Of the study, published in Nature, Dr. Steinman said, "This is the first time anyone has shown rather definitively that a virus is the trigger for multiple sclerosis."
Researchers at the Davis Lab and other collaborators are exploring how human killer cell immunoglobulin-like receptors (KIR) + CD8 + T cells target pathogenic T cells in active autoimmune disease. Their recent Science paper sheds light on "the mutiny called autoimmunity" and has important treatment implications for autoimmune diseases.
From exploring the underlying disease mechanisms of MS and chronic fatigue to examining neuroinflammation unique to Alzheimer’s disease to describing adaptive B-cell and T-cell responses to SARS-CoV-2 vaccination in people with MS on disease modifying immunotherapy, the many researchers and clinicians involved in Project BIG are involved in some of the most exciting research happening in the area of human autoimmune diseases.
Project BIG researchers, led by Dr. Jeffrey Dunn, are leading a number of studies exploring attenuated immunogenicity of the COVID vaccine in people with MS taking disease modifying therapies. A recent study showed that treatment with anti-CD20 and S1P modulator therapy was associated with attenuated immune response to COVID vaccination.
We are looking forward to continuing to disseminate our findings in leading journals and conferences. We will continue to embrace a multidisciplinary approach and innovative architecture. The impact of our translational research model is perhaps best evinced by the robust outcomes BIG efforts have yielded to date.
BOOKMARKED: MS NEWS
A "fascinating time" for research. The publications over the past several months linking EBV and MS have sparked broader interest in the long-term impacts of certain viruses. This article provides a brief history of how our knowledge about EBV has evolved over recent decades.
Rituximab and COVID-19. In a retrospective cohort study, people with MS treated with rituximab were at higher risk for hospitalizations from COVID-19. They were not, however, at higher risk of death or requiring ventilatory support. Time since infusion and dose were independent predictors of severity, suggesting a possible role for modified dosing or intervals. The authors suggested that people with MS treated with rituximab should take additional precautions to avoid exposure to COVID-19 in the five-months after an infusion.
AI-identified MS subtypes. In an effort to identify subtypes of disease that may influence treatment decisions, a team of scientists identified three new subtypes using MRI scans and artificial intelligence (AI) algorithms. The AI algorithms identified the following three patterns based on which area of the brain was first impacted: “cortex-led,” “normal-appearing white matter-led,” and “lesion-led.” The subtypes predicted disability progression and response to treatment suggesting utility for identifying patients for clinical trials and predicting response to treatments.
New medical device approved to target gait. A tongue stimulator medical device that sends electrical pulses to the tongue and through facial nerves was approved by the FDA to improve the walking gait of people with MS. In a randomized trial, people treated with the device showed improvements across multiple measures of gait.
Changes in emotional expression and recognition. Compared to a control group, people with MS showed both a greater difficulty in recognizing emotions, particularly emotions of a negative valence, and a heightened experience of emotions of a positive and negative valence.
BROADER BIG (BRAIN-IMMUNE-GUT AXIS)
Drafting the human microbiome in the fight against viruses. COVID-19 has spurred a heightened interest in understanding the role that the microbiome can play in fighting viral infections. Drawing on some of the preliminary evidence showing a connection between gut microbes and severity of COVID-19 infection, the author discusses the possible ways that gut microbes may be utilized to fight viruses.
The microbiome and schizophrenia. In examining the role of the gut microbiome on brain structure and function in schizophrenia, the authors found significant between-group differences in the gut microbiota and MRI indexes in people with schizophrenia compared to controls.
A blood-based diagnostic test to identify amyloid shows strong promise. This non-invasive blood-based test has shown promise in identifying brain amyloid status, with implications for early diagnosis of Alzheimer's disease.
[Listen] The Problem of Alzheimer’s. In this hour-long podcast episode, Dr. Jason Karlawish, author of The Problem of Alzheimer’s: How Science, Culture, and Politics Turned a Rare Disease into a Crisis and What We Can Do About It discusses the impacts of Alzheimer’s disease and other dementias on the person and their family and the complex history of funding and research for Alzheimer’s disease.
QUOTED
"Simplicity is the end result of long, hard work, not the starting point." Frederick Maitland
COMMITTED
Will you consider renewing your support for Project BIG in 2022?
We know that you show your generosity by giving your support, advocacy, money, time, and voice to many worthwhile causes and passions. Whether it’s by forwarding our The Big Brief newsletter, telling someone about our mission to unlock the cause and cure for multiple sclerosis and our commitment to high impact research, or making a 100% tax-deductible gift to Project BIG via Stanford Healthcare, we would love to count on your support as this year comes to end. 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
#ProjectBIG
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