Preventing neural graft rejection in Parkinson's patients

A research team led by The Florey Institute of Neuroscience and Mental Health has engineered a way to fool the immune system into accepting neural grafts as part of the body, rather than attacking them as foreign objects. Their breakthrough, published in the journal Cell Stem Cell, could signal an end to the reliance on drugs necessary to prevent graft rejection in Parkinson’s patients, as well as for other cell transplants.

As explained by lead author Professor Clare Parish, Florey Deputy Director and Head of Stem Cells and Neural Development, Parkinson’s disease is a neurodegenerative condition that causes specific nerve cells (neurons) to die, leading to symptoms that include difficulties moving, tremor, stiffness and impaired balance. Current medications treat the symptoms of Parkinson’s disease, but neural grafting is an emerging treatment to target the cause by replacing the dead neurons, with at least three major clinical trials in progress.

“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,” Parish said. “Unfortunately, these drugs carry their own risks and side effects.”

Parish said the research team has now engineered neurons which are “like those currently in clinical trials for Parkinson’s disease, but we’ve also given them an invisibility cloak. They can hide in plain sight from the immune system. This could mean an end to the need for anti-rejection drugs.”

Co-lead author Dr Chiara Pavan said the team tested the engineered neuronal grafts in mice with a ‘humanised’ immune system, and in rats modelling Parkinson’s disease.

“After receiving their neuronal graft, the mice showed no negative effects — which is a good indication that the human immune system will accept the neurons,” Pavan said. “In rats, the symptoms of Parkinson’s disease were abolished, indicating the cloaked neurons don’t lose their effectiveness against the disease.” The neurons also have an ‘off’ switch so that they can be activated if desired, to eliminate the risk of tumours developing from grafts.

Parish said it is an exciting result and that the technology has huge potential.

“We’ve made a cell product that in future could be implanted in people with Parkinson’s disease, reducing the need for anti-rejection drugs,” she said.

“Stem cells can be turned into any kind of cell, and we’ve effectively made them invisible to the immune system.

“This is the next generation of neurological treatment, and it could be used as a safe, off-the-shelf cell product suitable for treating diseases for which cell-based therapies are a viable option, such as stroke, Huntington’s disease, heart diseases and diabetes.”

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