Dopamine production in Parkinson’s patients is increasing exponentially: a study with stem cells at the Sloan Kettering Cancer Center

Stem cells appear to be poised to become a new treatment option for Parkinson’s and other brain diseases after many of the technical hurdles have been cleared.

Results published in March suggest that for three individuals who received the treatment, the cells have survived and are safe one year after surgery2. But the signs of benefit are mixed. One of the three people said that her husband’s face could be seen through a small section of her eye, but only after her cells had been replanted.

The trials were mainly designed to test safety and were small, involving 19 individuals in total, which is not enough to indicate whether the intervention is effective, says Parmar.

There were some people who got slightly better and others who didn’t get better according to a stem-cell researcher.

Although neither study used participants’ own cells, the results nevertheless represent welcome news for a huge number of people. In 2021, some 11.8 million individuals worldwide were living with Parkinson’s3, more than double the number 25 years earlier. The figures are increasing and could reach 25 million in the next quarter of a century, according to a modelling study.

The stem cells were injected to 18 sites across the putamen in both hemispheres — “to roughly fill up that region of the brain”, says Viviane Tabar, a neurosurgeon at the Memorial Sloan Kettering Cancer Center in New York City who conducted the US surgeries.

Five individuals received a dose of 0.9 million cells and 7 received 2.7 million cells, in the hope that 100,000 and 300,000 cells, respectively, would survive the surgery. A healthy brain has a lot of dopamine-producing cells. The recipients were given immune-suppressing drugs for one year after the surgery to prevent their bodies from rejecting the transplant.

Brain scans showed an overall increase in dopamine production, suggesting that some neurons survived the entire 18-month observation period, even after the participants stopped receiving immune-suppressing drugs.

For a typical Parkinson’s patient, “you would expect every year to get two to three points worse,” says Dr. Lorenz Studer, who directs the Center for Stem Cell Biology at the Sloan Kettering Institute in New York and is a scientific adviser to BlueRock.

The Potential and Limitations of Induced Pluripotent Stem Cells for Regeneration of the Eye, Brain, and Spine

In 2012, the discovery of a way to ‘reprogram’ mature mouse and human cells into a primitive state from which they could develop into any of the body’s cell types won Shinya Yamanaka, a biologist at Kyoto University in Japan, a half share of the Nobel Prize in Physiology or Medicine. His demonstration of how to make these cells, known as induced pluripotent stem (iPS) cells, also raised hopes that personalized treatments could soon follow, to regenerate damaged tissues such as those of the eye, brain and spine.

Three individuals received up to 5 million cells and 4 received up to 11 million cells, of which 150,000 and 300,000 cells, respectively, were expected to survive. “This low survival rate is a big problem that needs to be solved,” says Jun Takahashi, a neurosurgeon at Kyoto University in Japan, who led the trial. Participants were given immune-suppressing drugs for 15 months.

There are hints of an approaching medical revolution in Japan. Shiny white robots are tending dishes of cells, rows of incubators hum in new facilities, and a deluxe, plush-carpeted hospital is getting ready to welcome its first patients.

There is a need for both the policymakers and the public to be aware that careful and thorough evaluation of new science-based medical products is best for patients, researchers and organizations. Regenerative medicine is an exciting and promising science, and it has taken researchers decades to bring it to the point of clinical application. Regulators around the world must not put that promise at risk by rushing the final stage of the process.

The public isn’t willing to try it because of the high costs and large trials that aren’t clear of benefits, and because of concern over safety. We are close to realizing what the potential of these cells are and what the limits are.

Yamanaka promised his cells would not have to endure a bioethical stand-off that had been threatening the future of stem cells. iPS cells are not required to destruction of human embryos, which made them ethically less fraught. Furthermore, because they could be made from the cells of the person in need of treatment, they promised to offer transplantable tissues without the need for immune-suppressing drugs.

She and her team initially tried injecting a pool of donor-derived cells just under the retina, where they might form sheets on their own. The researchers weren’t able to control the location of the cells. They next tried growing strips of cells, 2 centimetres long and 200 micrometres thick. They used a tube to slide several of these strips onto the retina through a tiny incision in the eye, in the hope that they would expand into sheets.

It was a procedure that was not perfect. Self-derived, or ‘autologous’, cell therapies are time-consuming and expensive to make, and the large cell-sheets that researchers crafted for implantation required intrusive surgery. Takahashi says she chose this approach to ensure the highest chance of clinical benefit — to demonstrate to the world what was possible. It was intended to be the science-based best treatment.

The natural resistance to regeneration may be the reason for the difficulties. The clear covering of the eye that lets light in is maintained by stem cells and is one part of the eye that might benefit from cell therapies.

On the emergence of a Japanese company for the clinical development of iPS-cell therapies for rare diseases, says Markovian Svendsen

Nishida has since set up a start-up company, Raymei, which plans to launch a larger trial and aims to gain formal approval in three years. The next trial is crucial according to him.

Takahashi is a neurosurgeon and the director of Kyoto University’s Center for iPS Cell Research and Application (CiRA), an institute established by Yamanaka as a hub for iPS-cell research.

But, unlike his wife, he has not set up a company to develop the technology for manufacturing the cells and conducting the surgery. He has transferred that knowledge to a company in Osaka. He says that he is satisfied as a scientist. He had been focused on developing cell therapies for stroke.

Others are less concerned about Japan’s fast-track process for conditions that are rare or have few other treatment options. “In order to move this field forward quickly, you’re going to have to have an element of risk,” says Svendsen. “What I’ve seen in Japan has been pretty sensible; they are putting regulations in place.”

Treatments can be offered by companies with the national health system covering some of the costs. They must collect data to get full clinical approval.

The fast-track system also incentivizes companies to roll out as many interventions as possible before a product’s conditional approval expires, maximizing potential revenue. This has led some to call for the efficacy requirements for conditional approval to be raised.

Making Brain Transplants with a Two-Armed Robot Robot: Finding the Brain’s Best Source of Stimulated Neurotransplants

Masayo Takahashi has decided to use a white, muscular-looking two-armed robot to make her treatments. As cells are prepared to be used for transplant through a microscope it checks in on their progress using machine learning. In 4 months, it can produce enough cells for more than 800 individual treatments.

Such work has the potential to transform lives, but it is important that these therapies do not move into the clinic too quickly. Researchers must be allowed to take as much time as is necessary to complete safety and efficacy tests.

The early-stage trials that report the results show that the interventions were safe, and recipients of them experienced some improvements in their symptoms such as tremors and rigidity.

“If we’re missing neurons, we’re able to replace them,” Tabar says. The expectation is that these cells won’t function like cells that release a substance like dopamine. They are going to rebuild.

“They’re going to be there for a long, long time,” Schiess says. “So you have to follow up and see if there is tumor formation or something of that nature.”

“The idea is to place these progenitors where you need them to connect with the rest of the brain,” says Dr. Tabar, a stem cell scientist and chair of neurosurgery at Memorial Sloan Kettering Cancer Center.

Another challenge was creating and packaging large numbers of stem cells that could be easily delivered to surgeons. So researchers developed techniques that allowed them to freeze stem cells until they were needed.

It took more than a decade to figure out how to make dopamine cells. “It took us another 10 years to have the product that we would dare to put into patients.”

BlueRock is a division of a pharmaceutical giant, and surgeons have been given a high or low dose of the stem-cell product. The treatment was derived from cells that researchers had grown into immature brain cells.

The results indicate that we have the power to stop the disease in its tracks, says Dr. Mya Schiess, a professor at UTHealth Houston who was not involved in either study.