January 25th 2023
Researchers supported by the International Progressive MS Alliance’s Collaborative Research Network led by Professor Francisco Quintana (Brigham and Women’s Hospital) have created a new technique for studying cells that drive disease activity in people with MS. The team used this tool to identify two new targets for developing strategies to reduce disease activity in people with progressive MS. This team was recently given further funding by the Alliance to pursue promising compounds.
“Many major medical discoveries are made possible by advances in technology like this one reported by Dr. Quintana’s team,” said Dr. Robert Fox, Chair of the Alliance’s Scientific Steering Committee. “It’s exciting that Alliance investments led to this advancement, which not only identified new targets for potential treatment, but also found a way that may speed the identification of new approaches for treating progressive MS.”
- Background: The International Progressive MS Alliance is supporting a collaborative network led by Francisco Quintana, Ph.D., of Harvard Medical School, to develop promising compounds that target critical disease activities that drive progressive MS and brain injury. Dr. Quintana is focused on star-shaped cells known as astrocytes. Under normal conditions, astrocytes are involved in many different activities to keep the brain functioning. This team has identified a subtype of astrocytes linked to disease activity in mice with MS-like disease. Detecting and analyzing such cell subtypes is difficult and expensive, however.
- This Study: Dr. Quintana and colleagues have developed a new method of studying astrocytes that involves isolating them in droplets, detecting genetic material and then sorting the droplets to identify cell types. Called “FIND-seq,” this method reduces the technical difficulties and costs compared to other techniques. The team applied this method to cells obtained from mice with MS-like disease and individuals with MS.
- Results: Using FIND-seq, Dr. Quintana’s group was able to pinpoint the disease-causing subtype of astrocytes. They also were able to identify two previously undescribed molecules that restricted the disease-causing capabilities of these astrocytes.
- Meaning: The study described a new method that may accelerate how researchers study brain cells like astrocytes. This study also revealed two molecules that can now be studied as targets for developing therapeutic strategies for reducing disease activity in progressive MS. Further research is necessary to determine whether targeting these molecules safely and effectively limits progression in models of MS, and eventually, studies in people with progressive MS.
“Identification of astrocyte regulators by nucleic acid cytometry” by Drs. Iain C. Clark, Michael A. Wheeler, Hong-Gyun Lee, Zhaorong Li, Liliana M. Sanmarco, Shravan Thaploo, Carolina M. Polonio, Seung Won Shin, Giulia Scalisi, Amy R. Henry, Joseph M. Rone, Federico Giovannoni, Marc Charabati, Camilo Faust Akl, Dulce M. Aleman, Stephanie E. J. Zandee, Alexandre Prat, Daniel C. Douek, Eli A. Boritz, Francisco J. Quintana & Adam R. Abate is published in Nature (published online January 4, 2023).