Sana Biotech's Study in Nature Biotech Shows Promise of Stem Cell-Derived Glial Transplants

Sana Biotechnology, Inc., a company dedicated to advancing patient care through engineered cells, has announced the publication of significant research in Nature Biotechnology. The study, titled “Young glial progenitor cells competitively replace aged and diseased human glia in the adult chimeric mouse brain,” underscores the potential of healthy transplanted human glial cells in replacing diseased cells in the brains of experimental mice.

The research demonstrated that healthy wild-type (WT) pluripotent stem cell-derived glial progenitor cells (hGPCs) could outcompete and replace mutant Huntingtin (mHTT)-expressing glial cells when transplanted into adult mice. These mice had been previously introduced to the mutant cells at a neonatal stage. Over time, the healthy hGPCs not only eliminated the diseased cells but also repopulated the brain with healthy cells. This finding serves as an additional proof-of-concept for Sana Biotechnology’s SC379, a pluripotent stem cell-derived glial progenitor cell product candidate, suggesting its potential as a therapeutic intervention for central nervous system disorders.

Steve Harr, President and CEO of Sana Biotechnology, emphasized the significance of these findings. He noted that the ability of healthy human glial cells to engraft and function in vivo, outcompeting diseased cells, supports the potential application of SC379 in treating numerous neurological conditions. These conditions include secondary progressive multiple sclerosis, childhood myelin disorders such as Pelizaeus-Merzbacher disease, Huntington’s disease, and other glial cell-related diseases. Harr revealed that Sana aims to start clinical testing of SC379 by 2025.

Dr. Steve Goldman, Sana’s Head of CNS Therapy and the lead author of the study, elaborated on the implications of the research. He pointed out that diseases affecting glial cells are among the most common and debilitating in neurology. This is because glial cells include both oligodendrocytes, which produce myelin, and astrocytes, which support neurons. The research team has successfully developed methods to produce and isolate glial progenitor cells from pluripotent stem cells, ensuring the purity and quantity needed to replace diseased cell populations effectively.

In the experimental study, the researchers used human glial chimeric mice to model the competition between healthy and diseased human glial cells. Genetically tagged WT hGPCs, derived from human embryonic stem cells (hESCs), were introduced into the brain striata of adult mice previously engrafted with hGPCs expressing the Huntington’s disease mutation. The results showed that the healthy WT cells gradually overtook and replaced the diseased cells, repopulating the striatum significantly.

The study also explored the effects of introducing younger hGPCs into adult mice previously engrafted with older glial cells derived from the same healthy cell line. The younger cells rapidly infiltrated the brain tissue, eventually replacing the older cells. This replacement was associated with the apoptotic death of the older cells, triggered by the presence of the younger hGPCs, leading to a substantial recolonization of the tissue with healthy cells.

Sana Biotechnology, headquartered in Seattle, is committed to developing engineered cell therapies that repair and control genes, replace damaged cells, and make these treatments broadly available to patients. The company operates in multiple locations, including Cambridge, South San Francisco, Bothell, and Rochester.