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First-of-its-kind clinical trial will use reprogrammed adult stem cells to treat Parkinson’s

Jun Takahashi (left) and colleagues explained their plans for a trial in Parkinson’s disease patients at a press conference at Kyoto University in Japan today.

Researchers in Japan today announced the launch of a clinical trial to treat Parkinson’s disease with neurological material derived from induced pluripotent stem (iPS) cells, mature cells chemically manipulated to return to an early stage of development from which they can theoretically differentiate into any of the body’s specialized cells.
The study team will inject dopaminergic progenitors, a cell type that develops into neurons that produce dopamine, directly into a region of the brain known to play a key role in the neural degeneration associated with Parkinson’s disease. The effort is being led by Jun Takahashi, a neurosurgeon at Kyoto University’s Center for iPS Cell Research and Application (CiRA), in cooperation with Kyoto University Hospital.

Parkinson’s disease results from the death of specialized cells in the brain that produce the neurotransmitter dopamine. A lack of dopamine leads to a decline in motor skills, resulting in difficulty walking and involuntary trembling. As the disease progresses it can lead to dementia. The trial strategy is to derive dopaminergic progenitors from iPS cells and inject them into the putamen, a round structure located at the base of the forebrain. Surgeons will drill two small holes through a patient’s skull and use a specialized device to inject roughly 5 million cells.

Studies in animals have shown that the progenitors differentiate into dopaminergic neurons inside the body and engraft into the brain. Takahashi’s group reported last year that monkey models of Parkinson’s disease showed significant improvement lasting 2 years after getting injections of neurons prepared from human iPS cells.
Rather than make patient-specific iPS cells, CiRA has adopted the strategy of deriving stocks of iPS cells from healthy donors with specific cell types that are less likely to cause immune rejection. “Using stocks of cells, we can proceed much more quickly and cost-effectively,” CiRA Director Shinya Yamanaka, who won a share of the Nobel Prize in Physiology or Medicine in 2012 for discovering how to create iPS cells, told Science in 2017. As an added precaution, the patients will receive a common immunosuppressant in tandem with the progenitors.
Patient recruitment started today at 5 p.m. local time, when Kyoto University Hospital posted the patient recruitment notice on its website. The team plans to recruit seven patients and follow them for 2 years postinjection.
This is the third human trial using iPS cells approved in Japan. The first, using retinal cells derived from iPS cells to replace eye tissue damaged by age-related macular degeneration (AMD), was launched in 2014 and is being led by Masayo Takahashi—Jun Takahashi’s wife—of the RIKEN Center for Developmental Biology in Kobe. The AMD treatment was initially reported to be safe, though there has been one reported adverse event. Earlier this year, a team at Osaka University in Japan won conditional approval for an iPS cell–based study for ischemic heart disease.