Using Human iPSC Models to Dissect PIRA Mechanisms in Progressive Multiple Sclerosis: Valentina Fossati, PhD

WATCH TIME: 3 minutes

“These human iPSC models allow us to separate what is cell intrinsic from what is driven by the surrounding environment, which is extremely difficult to do in vivo. That distinction is critical if we want to understand the biology underlying PIRA rather than just describing its clinical consequences.”

Progression independent of relapse activity (PIRA) has emerged as a defining concept in multiple sclerosis, particularly as clinicians recognize that disability accumulation often continues despite suppression of inflammatory relapses. While clinical and imaging data have helped characterize PIRA phenotypically, the biological mechanisms driving this process remain poorly defined, limiting the development of targeted therapies for progressive disease.

At the 2026 Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS), held February 5-7 in San Diego, California, Valentina Fossati, PhD, led a presentation focusing on induced pluripotent stem cell (iPSC) technology and its effect on disease modeling. Her presentation focuses on how these patient-specific stem cell models are used in multiple sclerosis research to produce oligodendrocytes, microglia, astrocytes, and neurons, including in co-culture and 3D organoid systems that better mimic human brain tissue.

During the meeting, Fossati, a senior research investigator at the New York Stem Cell Foundation, sat down to discuss her presentation in depth, including the ways iPSC models can be leveraged to study PIRA in a controlled, reductionist manner. She outlined how increasingly complex co-culture and organoid models can be used to examine glial crosstalk, neuroinflammatory signaling, and myelination processes while minimizing confounding variables present in animal models and postmortem tissue. Fossati also discusses current limitations of these platforms, including the absence of vasculature and peripheral immune components, and how ongoing technical advances may further strengthen their relevance to progressive MS research.

Click here for more 2026 ACTRIMS Forum coverage.