Stem Cell Grafts Reverse Parkinson’s Symptoms in Rats

A research team in Arizona has described a process for converting non-neuronal cells into functioning neurons able to take up residence in the brain, form functioning synapses, and dispense dopamine—a breakthrough that raises hopes for restoring functions undermined by Parkinson’s disease.  

Over 10 million people are affected by Parkinson’s disease worldwide. The disease’s most obvious symptom—rigidity, tremor, and postural instability—arises from the damage it inflicts on the midbrain, robbing the brain of key neurotransmitter, dopamine. Other symptoms of the disease can include depression, anxiety, memory deficit, hallucinations and dementia. Current Parkinson’s disease therapies, which include use of the drug L-DOPA, are only able to address some of the motor symptoms of the disease and may produce serious, often intolerable side effects after 5–10 years of use.

In a new proof-of-concept study, Arizona State University-Banner Neurodegenerative Disease Research Center and School of Life Sciences researcher Jeffrey Kordower and colleagues report a group of experimentally engineered cells that performs optimally in terms of survival, growth, neural connectivity, and dopamine production when implanted in the brains of rats. The study also demonstrates that such neural grafts can effectively reverse motor symptoms due to Parkinson’s disease.

The study’s experiments included induced pluripotent stem cells (iPSCs) cultured for 24 and 37 days, but those cultured for 17 days prior to their differentiation into dopaminergic neurons were markedly superior, capable of surviving in greater numbers and sending out their branches over long distances. “That's important,” Kordower says, “because they're going to have to grow long distances in the larger human brain and we now know that these cells are capable of doing that.”

Rats treated with the 17-day iPSCs showed remarkable recovery from the motor symptoms of Parkinson’s disease. The study further demonstrates that this effect is dose dependent. When a small number of iPSCs were grafted into the animal brain, recovery was negligible, but a large complement of cells produced more profuse neural branching, and complete reversal of Parkinson’s symptoms.

A first-of-its-kind clinical trial is set to test stem cell replacement therapy for a specific population of Parkinson’s disease sufferers with a mutation in the gene parkin. Such patients suffer from the typical symptoms of motor dysfunction found in general or idiopathic Parkinson’s, but do not suffer from cognitive decline or dementia. This cohort of patients provides an ideal testing ground for cell replacement therapy. If the treatment is effective, larger trials will follow, applying the strategy to the version of Parkinson’s affecting most patients stricken with the disease. The trial will be conducted at various locations, including the Barrow Neurological Institute in Phoenix, with Kordower as principal investigator.

“We cannot be more excited by the opportunity to help individuals who suffer from this genetic form of Parkinson’s disease, but the lessons learned from this trial will also directly impact patients who suffer from sporadic, or non-genetic forms of this disease,” Kordower says.

The research  appears in the current issue of the npj journal Nature Regenerative Medicine.