Sana Biotechnology Highlights Novel In Vivo Preclinical Data Showing Potential for Pluripotent Stem Cell-Derived Human Glial Progenitor Cell Transplantation as a Treatment for Huntington’s Disease and Other Glial-Based Neurodegenerative Conditions

Sana Biotechnology, Inc. recently highlighted Nature Biotechnology has published a paper titled Young glial progenitor cells competitively replace aged and diseased human glia in the adult chimeric mouse brain. This paper showed that when healthy wild-type (WT), pluripotent stem cell-derived glial progenitor cells (hGPCs) – the cells that give rise to the glial support cells of the brain – were transplanted into adult mice that had been neonatally transplanted with mutant Huntingtin (mHTT)-expressing hGPCs, the healthy cells outcompeted and eliminated the diseased glia, ultimately repopulating the brain with the healthy transplanted cells. These data establish an additional proof-of-concept for the development of SC379, Sana’s pluripotent stem cell-derived GPC product candidate, as a potential therapy to deliver healthy allogeneic GPCs to patients with certain central nervous system disorders.

“It is remarkable to see that healthy human glial cells can engraft and function in vivo, and succeed in outcompeting resident glial cells, thereby eradicating the diseased cells from the brain of the mice,” said Steve Harr, Sana’s President and Chief Executive Officer. “We have designed SC379 as a potential glial cell replacement therapy, and these findings support its possible application in a large number of neurological indications, such as secondary progressive multiple sclerosis and the childhood myelin disorders like Pelizaeus-Merzbacher disease, as well as Huntington’s disease and other diseases of glial cells. Our goal is to begin clinical testing of SC379 as early as 2025.”

Steve Goldman, MD, PhD, Sana’s Head of CNS Therapy and lead author on the paper, added “Diseases of glial cells are among the most prevalent and debilitating conditions in neurology, as they include both the myelin-producing oligodendrocytes and the astrocytic support cells of neurons. We have developed the methods for producing and isolating glial progenitor cells – which produce both oligodendrocytes and astrocytes – from pluripotent stem cells, and for delivering them in the purity and quantity necessary to replace diseased cell populations.”

In the study, human glial chimeric mice were used to model the impact of competition between healthy and diseased human glia in vivo. Genetically tagged WT hGPCs derived from human embryonic stem cells (hESCs) were engrafted into the striata of adult mice, which were neonatally chimerized with hGPCs derived from a sibling line with Huntington’s disease (HD). Over time, the group found that the healthy WT cells overtook the HD cells and repopulated the striatum with healthy cells (54 weeks, P < 0.0001; 72 weeks, P < 0.0001).

The study also evaluated the impact of engrafting younger hGPCs into adult mice that had been neonatally engrafted with separately tagged older glia derived from the same healthy cell line. The data demonstrated that the younger hGPCs rapidly infiltrated the striatum and eventually replaced the older hGPCs, leading to a substantial recolonization of the tissue (P < 0.0001). This was associated with the apoptotic death of the older cells, which was triggered by the introduction of the younger hGPCs and enabled a repopulation of the mouse striatum with the younger cells.

Sana Biotechnology, Inc. is focused on creating and delivering engineered cells as medicines for patients. We share a vision of repairing and controlling genes, replacing missing or damaged cells, and making our therapies broadly available to patients. We are a passionate group of people working together to create an enduring company that changes how the world treats disease. Sana has operations in Seattle, WA, Cambridge, MA, South San Francisco, SF, Bothell, WA, and Rochester, NY. For more information, visit https://sana.com/.