Early-Stage Parkinson’s Therapy Using Stem Cell Transplantation in the US Brain Has Survived One Year After Surgery

Now that many of the technical hurdles have been cleared, stem cells appear poised to offer a new treatment option for Parkinson’s, and perhaps other brain diseases like epilepsy or Alzheimer’s.

Results published in March suggest that for three individuals who received the treatment, the cells have survived and are safe one year after surgery2. There are some signs of benefit. One of the three individuals said she could see her husband’s face clearly for the first time in ten years, but only through a small section of her eye, where the cells had been transplanted.

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.

“Some people got slightly better and others didn’t get worse,” says Jeanne Loring, a stem-cell researcher at Scripps Research in La Jolla, California, which could be due to the relatively small number of cells transplanted in these first early-stage trials.

The results of both studies represent welcome news for a lot of people, because neither study used participants own cells. In 2021, some 11.8 million individuals worldwide were living with Parkinson’s3, more than double the number 25 years earlier. The study states that the number could hit 25 million in the next 25 years.

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.

The hope was that 100,000 and 300,000 cells, received by seven people, would survive the surgery. A healthy brain contains a lot of dopamine-producers. The recipients were given immune-suppressing drugs for one year after the surgery to prevent their bodies from rejecting the transplant.

Brain scans show an overall increase in dopamine production, and suggest that some neurons survived even after participants stopped taking immune- suppressing drugs.

“For a Parkinson’s patient, you would expect each 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.

Bioethical Implications of Using Donor-Detained Stem Cells for the Advancement of Regenerative Medicine in Japan

The Kyoto researchers used stem cells from a patient instead of an embryo in their second study.

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. The participants were treated with drugs for 15 months.

Scientists launched clinical trials and start-up firms. Large biotech companies swooped in, investing even more in manufacturing hubs. Now, medical facilities are preparing to welcome a rush of patients from Japan and abroad. According to Masayo Takahashi, president of Vision Care,generative medicine in Japan is moving very quickly. In 2014, she became the first to treat someone with cells derived from iPS cells.

There is a need to raise awareness among both policymakers and the public of why careful and thorough evaluation of new science-based medical products is best for all concerned — patients, researchers and organizations taking such interventions to the clinic. Regenerative medicine is an exciting and promising science, and it has taken researchers decades to bring it to the point of clinical application. The final stage of the process should not be rushed by the regulators around the world.

It has not yet received approval, the costs are high, and concerns about safety could affect the willingness of people to try this treatment. “We’re going to have to understand what the potential is and what the limits are.”

Yamanaka’s iPS cells promised to bypass a bioethical stand-off that had threatened the potential of embryonic stem cells for a decade. Because production of iPS cells doesn’t require the destruction of human embryos, they were considered 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 tried putting donor-derived cells under the eye, where they could form sheets on their own. But the researchers had limited control over where the cells grew. They tried growing strips of cells that were over 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 with practical limitations, however. Large cell sheets required intrusive surgery in order to make, and are self-derived, or autologous, cell therapies. Takahashi says she chose this approach to ensure the highest chance of clinical benefit — to demonstrate to the world what was possible. It was meant to be the best treatment.

The difficulties might be related to the eye’s natural resistance to regeneration. The clear covering of the eye called the cornea is maintained by a pool of stem cells, which is why it might benefit from cell therapies.

Tameside Nishida: Managing the Fast Track for Clinical Development of Neurosurgery Cell Therapies in Japan and the Role of the Fast-Track Mechanism

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 very important, he says.

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 transferred that knowledge to an Osaka-based pharma company. He says he is sort of satisfied as a scientist. He is now concentrating 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. I have seen japan putting regulations in place and they are pretty sensible.

Companies can offer the treatments, with costs mostly covered by the national health system. They have to keep collecting data to get a 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. Some people want to raise the efficacy requirements for approval.

Making Human Embryonic Stem Cells for Macular Degeneration: A Robot Approach to Delivery to Neurons to Surgeons

Masayo Takahashi has chosen a more portable manufacturing model for her macular-degeneration treatments: a white, muscular-looking, two-armed robot. The machine learns and checks the progress of cells as they are prepared for a transplant. It can make enough cells in 4 months for 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. To complete safety and efficacy tests researchers must take as long as is necessary.

Both studies, which are reporting the results of early-stage clinical trials, show that the interventions were safe, and that, on average, the recipients experienced measurable improvements in typical symptoms such as tremor and rigid movements.

Tabar says that if we are missing neurons, we are able to replace them. The expectation is that the cells will not function like dopamine releasing cells. They are going to rebuild circuitry.

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

Dr. Tabar is a Stem Cell scientist and the chair of Neurosciences at Memorial Sloan Kettering Cancer Center.

The challenge was packaging large volumes of stem cells that could easily be delivered to surgeons. Researchers were able to freeze stem cells until needed.

It took us nearly 10 years to come up with a way to make dopamine cells. It took 10 years for us to get the product we would be willing to put into patients.

Surgeons administered either a low or high dose of a stem-cell product from BlueRock Therapeutics, a subsidiary of biotech and pharmaceutical giant Bayer. The treatment was derived from human embryonic stem cells, which researchers had coaxed into becoming immature brain cells called neuron progenitors.

The results show that we have the potential to stop this disease in its tracks, according to Dr. Mya Schiess, who was not involved in either study.