New research kindles excitement around stem cell therapies for Parkinson’s

 The most effective drug for Parkinson’s disease hasn’t changed in 50 years. But fresh research published in one of the country’s top scientific journals is helping build the case for a more cutting-edge approach that uses stem cells to restore important brain functions.

The second most common neurodegenerative illness, Parkinson’s is caused by the loss of certain nerve cells. These cells produce a chemical messenger, dopamine, that plays a crucial role regulating movement. Since the 1970s, a drug called levodopa, which the body converts into dopamine, has been the mainstay treatment for combating the tremors, slowness, stiffness and balance issues that come with Parkinson’s.

Levodopa doesn’t stop the disease, however, so scientists have spent decades trying to find a more permanent fix. The latest development in that search comes from two clinical trials testing stem cell-derived therapies transplanted into the brains of Parkinson’s patients.

The first of those trials, conducted at the Kyoto University Hospital in Japan, evaluated seven people who received what are essentially blank slate cells that can turn into dopamine-producing neurons. These cells were created using a technology pioneered at Kyoto University, where roughly 20 years ago, scientists discovered how to reset some adult human cells to act like stem cells.

The study’s main focus was safety. Results, published Wednesday in Nature, show no serious adverse events were reported, though researchers did identify 73 mild to moderate events. Importantly, there was no evidence the introduced cells started growing in an unchecked, tumor-like fashion — a major concern with stem cell implants.

The study also explored whether this therapy had any effect on patients’ disease. Two years post-treatment, the six participants who were evaluable had gotten better on a scale clinicians use to measure the severity of Parkinson’s motor symptoms. Researchers looked at what’s known as “on” time, when medications are adequately controlling these symptoms, as well as the opposite “off” time, and found scores improved an average of 36% and 20%, respectively.

Another test indicated that dopamine-producing cell activity had increased substantially. This was determined through a technique in which researchers strap a radioactive element to a molecule of levodopa and then use a PET scan to follow its path through the nervous system, somewhat like how a submarine tracks objects on a sonar display.

The second trial took place at sites throughout the U.S. and Canada, and employed a different kind of stem cell that comes from human embryos. It enrolled a total of 12 participants and followed them for a year post-transplant.

Similar to the Japan study, there were no deaths, serious adverse events or tumor-like tissue growth related to the introduced cells. Trial runners did report two serious events overall. One participant was hospitalized with COVID-19, while another had a seizure that was attributed to the surgical procedure.

The trial also saw improvements in “off” scores on that disease severity scale and positive results from the radioactive levodopa test.

The cell therapy tested, called bemdaneprocel, is being developed by Bayer subsidiary BlueRock Therapeutics, which back in August 2023 announced some of the data published Tuesday. The company expects to start a Phase 3 trial before the end of June.

Hideyuki Okano, a stem-cell scientist at Keio University in Tokyo, argues more research is needed to confirm these types of cell therapies are effective against Parkinson’s.

Still, in an accompanying Nature editorial, he called the new trial results “encouraging” because they suggest treating Parkinson’s patients with donor cell transplants is likely safe. That both trials “proved to be safe, and hinted at possible efficacy, is an important step towards the establishment of this cell therapy for Parkinson’s disease in wider society,” he wrote.

Cell therapy for Parkinson’s isn’t a new idea. In 1989, a team led by neuroscientist Olle Lindvall performed the first cell transplantations for Parkinson’s patients. While the landmark study didn’t show a major therapeutic benefit, a few interesting signals encouraged the research community to keep exploring.

One ethical concern from that trial was that it used a relatively large amount of tissue derived from aborted fetuses. In the decades since, Parkinson’s and cell biology experts have made significant progress identifying other, less controversial sources of stem cells that can be scaled more easily.

A milestone of that work came in 2020, when the technique invented at Kyoto University was used to turn a Parkinson’s patient’s own skin cells into the early stages of dopamine-producing neurons, which were then implanted into his brain.

According to Okano, as of December, there were 115 clinical trials testing 83 products derived from “pluripotent” stem cells. And among those targeting central nervous system disorders, the ones for Parkinson’s disease are at a more advanced stage of development.

Further behind Bayer and BlueRock, Aspen Neuroscience, a San Diego-based biotechnology company, has a Parkinson’s therapy derived from patients’ own cells currently in early-stage human testing.

https://www.biopharmadive.com/news/parkinsons-stem-cell-therapy-nature-studies/745519/