SEP 14, 2021 7:00 AM PDT

Extinguishing Fires in the Brains of MS Patients

WRITTEN BY: Tara Fernandez

A closer look at the brains of patients with aggressive, debilitating forms of multiple sclerosis (MS) reveals some striking features. Among them, the presence of “smoldering” inflammatory hotspots. After intense scrutiny, neuroscientists have finally nailed down the cells that drive these regions of heightened inflammation, findings that lay the groundwork for next-generation therapies to treat progressive MS.

Previously, neural immune cells called microglia were thought to be responsible for initiating and expanding these neural lesions. Microglia are dispersed throughout the brain and spinal cord are among the core protectors of the central nervous system, removing damaged cells and resisting infections. However, in MS patients, microglia go into overdrive, churning out a cocktail of inflammatory factors that devastate surrounding neural tissues. However, the other cells that may be contributing to this uncontrolled inflammation have remained elusive.

Fortunately, single-cell RNA sequencing technology is helping to shed light on these long-standing mysteries, empowering scientists with the ability to collect data on gene activity signatures within individual cells. Researchers at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS) leveraged this platform to analyze a panel of post-mortem brain tissues from MS patients and healthy controls.

In their work, detailed in the high-impact journal Nature, the researchers describe the genetic profiling of a total of over 66,000 brain cells. The data collected was consolidated as the first cellular blueprint of MS chronic lesions, which included valuable data on both gene expression on an individual cell level and how these cells interact with each other.

Fascinatingly, the team’s analysis revealed that microglia only made up around a quarter of the immune cells present in MS brain lesions—a diverse ecosystem of immune cells including astrocytes and lymphocytes operated in unison to contribute to the elevated inflammation.

“Our dataset is very rich. The beauty of having such a detailed map is that now we have a better understanding of the entire network of cells involved in smoldering inflammation,” said Martina Absinta, one of the researchers involved in the study.

The investigation also revealed a clear connection between a complement protein called complement component 1q (C1q) and rampant neuroinflammation in the brains of MS patients. Experimental mouse models lacking the C1q gene displayed much less tissue inflammation than their wild-type counterparts. Together, the authors believe that their discoveries finally open up exciting new possibilities in MS drug development, which up to now have offered no clinical solutions for neither directly targeting active brain lesions nor curing the disease altogether.

 


 

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
You May Also Like
AUG 03, 2021
Health & Medicine
Viruses and Autoimmunity: What Pandemics Have Taught Us
AUG 03, 2021
Viruses and Autoimmunity: What Pandemics Have Taught Us
COVID-19 infections have given rise to COVID long haulers, people who had COVID and continue to have symptoms months aft ...
AUG 27, 2021
Health & Medicine
Blood Group and COVID-19 Susceptibility- An Ongoing Debate
AUG 27, 2021
Blood Group and COVID-19 Susceptibility- An Ongoing Debate
Since their discovery, there has been an interest in how ABO blood groups and infectious diseases may be related. In add ...
SEP 07, 2021
Health & Medicine
Think you can pay back your sleep debt this weekend? Think again.
SEP 07, 2021
Think you can pay back your sleep debt this weekend? Think again.
Researchers find that even one night of sleep loss results in impaired functioning and well being.
SEP 27, 2021
Cancer
Inflammation Promotes Pancreatic Cancer Progression
SEP 27, 2021
Inflammation Promotes Pancreatic Cancer Progression
Inflammation occurs when the immune response, including immune cells and mediators they produce, protect you from danger ...
OCT 07, 2021
Cancer
Dual Threat: CAR T Cells Modified to Target Two Neuroblastoma Antigens
OCT 07, 2021
Dual Threat: CAR T Cells Modified to Target Two Neuroblastoma Antigens
Neuroblastoma is a cancer of immature nerve cells found in various areas, including the adrenal glands, neck, chest ...
OCT 18, 2021
Genetics & Genomics
A Decade After Gene Therapy, SCID Patients Are Doing Well
OCT 18, 2021
A Decade After Gene Therapy, SCID Patients Are Doing Well
For decades, scientists have been trying to find ways to cure disorders that can be traced back to an error in one gene. ...
Loading Comments...