Australian scientists have successfully engineered human brain cells that can evade the immune system, effectively reversing Parkinson's disease symptoms in rats without the need for immunosuppressive drugs. The groundbreaking research, published in Cell Stem Cell, marks a significant advancement toward developing "universal" cell therapies that could be transplanted into any patient.
Engineering an Immune "Invisibility Cloak"
Researchers at the Florey Institute of Neuroscience and Mental Health in Melbourne modified human pluripotent stem cells (hPSCs) to overexpress eight specific immunomodulatory genes. These genes, naturally found in placenta and cancer cells, allow the engineered neurons to hide from immune surveillance.
"We've engineered neurons which are like those currently in clinical trials for Parkinson's disease, but we've also given them an invisibility cloak," explained Professor Clare Parish, Deputy Director at the Florey Institute and lead author of the study. "They can hide in plain sight from the immune system. This could mean an end to the need for anti-rejection drugs."
The modified stem cells were successfully differentiated into dopamine-producing neurons—the specific cell type that degenerates in Parkinson's disease. When transplanted into "humanized" mice with human-like immune systems, the engineered cells avoided rejection, confirming their immune-evasive properties.
Functional Improvement in Parkinson's Models
To test therapeutic efficacy, the team transplanted the cloaked neurons into rats treated with a neurotoxin that mimics Parkinson's disease symptoms. Twelve weeks after transplantation, the animals showed significant improvement in muscle function.
"In rats, the symptoms of Parkinson's disease were abolished, indicating the cloaked neurons don't lose their effectiveness against the disease," said Dr. Chiara Pavan, a neuroimmunology specialist at The Florey and co-lead author of the paper.
The researchers also incorporated a safety mechanism—an "off switch" that can deactivate the cells if necessary, reducing the risk of tumor development from the grafts.
Eliminating the Need for Immunosuppression
Current cell transplantation approaches require patients to take immunosuppressant medications, which carry significant risks including increased susceptibility to infections, elevated cancer risk, and tissue damage that ultimately shortens recipient lifespan.
"Neural grafting is an emerging treatment to replace dead neurons," Professor Parish noted. "Human neural graft trials are underway overseas but, as with other types of organ or cell transplants, patients need to stop their body rejecting the graft by taking immunosuppressant drugs several times a day. Unfortunately, these drugs carry their own risks and side effects."
By creating cells that naturally evade immune detection, this research could eliminate the need for these problematic medications while maintaining therapeutic efficacy.
Broader Applications Beyond Parkinson's
The implications of this technology extend far beyond Parkinson's disease. The researchers suggest their approach could be adapted to create immune-evasive versions of various cell types.
"Stem cells can be turned into any kind of cell, and we've effectively made them invisible to the immune system," said Professor Parish. "This is the next generation of neurological treatment, and it could be used as a safe, off-the-shelf product suitable for treating diseases for which cell-based therapies are a viable option, such as stroke, Huntington's disease, heart disease and diabetes."
Roger Barker, a neuroscientist at the University of Cambridge who was not involved in the study, described the approach as "clever and useful" and "of clear importance to the field," noting that the engineered cells differentiate and behave normally despite their genetic modifications.
The collaborative research involved scientists from the University of Melbourne, Monash University, The University of Sydney, the Walter and Eliza Hall Institute, the Centenary Institute of Cancer Medicine and Cell Biology in Australia, and Mount Sinai Hospital in Toronto, Canada.
As clinical trials of neural grafts for Parkinson's disease continue to advance globally, this innovation could represent the next evolution in cell therapy—one that makes universal, off-the-shelf treatments a reality without the burden of lifelong immunosuppression.
