Dr. Sameera Zia
Work done at University of Alberta
Article citation
Zia, S., Traetta, M.E., Baaklini, C.S., Hammond, B.P., John, R.K., Souter, K.M., Meijns, N.R.C., Afun, L.A., Panda, S., Ibanez, F.G., Burr, M.K., Dhupia, E., Rathod, A.M., Faria, A.O., Zaveri, D., Challa, S., Hahn, E., Manesh, S.B., Lee, K.V., Ho., M.F.S., Friedman, T.N., Maguire, A.D., Pang, A., Farkas, O., Szulc, B., Tenorio, L., Vyas, D., La Caprara, O.R., Tetzlaff, W., Sinha, S., Duncan, G.J., Voronova, A., Kerr, B.J., Tremblay, M., Biernaskie, J., Schenk, G.J., Plemel, J.R. Age-related impaired remyelination is associated with dysregulated microglial transition. Nature Communications; 2025
New therapeutic targets for Multiple Sclerosis identified by studying the role of microglia in myelin repair
Multiple sclerosis (MS) is a neurological disease that affects over 100,000 Canadians and is the leading cause of neurological disability amongst people ages 20-40 years. It is a chronic, autoimmune disease where the immune system attacks the protective myelin sheath covering nerves in the brain and spinal cord, disrupting signal transmission. It is associated with loss of motor, visual, sensory, autonomic and cognitive functions. Microglia, the immune cells of the central nervous system, are essential for efficient myelin regeneration, or remyelination—a process that occurs naturally in people with MS but is often inadequate and declines with age. In this article, Sameera Zia, working in the laboratory of Jason Plemel at the University of Alberta, uncovered central processes during myelin sheath repair by probing the immune basis of repair in multiple sclerosis (MS). They identified novel immune states present in brains of people with MS that can be targeted to repair brain lesions.
Prior to this study, it was known that brain-specific immune cells called microglia formed environment-specific states; however, the states present throughout remyelination and their differences in young and aged environments were unknown. Here, the researchers used mouse models of remyelination and single-cell RNA sequencing to identify novel microglial states specific to the key stages of remyelination, each with a distinct functional signature. They showed that microglia first adopted states that engaged in pro-repair pathways and then transitioned back into states like baseline microglia. They also found that aging disrupted either the emergence or resolution of these states, identifying states associated with successful repair in young environments that were dysregulated with age. One of the remyelination-specific states identified was also enriched in human MS autopsy tissue, demonstrating strong translational relevance.
This work provides the first blueprint of microglial states that underlie effective remyelination. These states, along with their active gene regulatory networks, secreted ligands, and expressed receptors, now serve as actionable therapeutic targets. Mapping these states also opens the possibility of developing biomarkers to measure successful remyelination in people with MS.
The identification of key remyelination-related microglial states allowed the researchers to leverage this published data and identify candidate medications to promote remyelination. This data was used to search databases for drugs to augment beneficial microglial states, which we are now being tested in both in vitro and in vivo models.
About Sameera Zia
Dr. Zia led this project as a Ph.D. candidate in Dr. Jason Plemel’s lab at the University of Alberta. Her work focusses on uncovering the immune basis of repair in white matter pathologies using bioinformatics and in vivo and in vitro tools.
Sources of funding
This project was funded by operating grants from Canadian Institutes of Health Research, National Science and Engineering Research Council of Canada, the University of Alberta Department of Medicine and Multiple Sclerosis Centre, the University Hospital Foundation Medical Research Competition, and in part by a Pilot Grant (#NMSS PRG PP-1912-35420) from the National Multiple Sclerosis Society. This work was also supported by the US Department of Defense through the Multiple Sclerosis Research Program under Award No. W81XWH-21-1-0797. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.