The symptoms of Parkinson’s are getting better in stem-cells trials

Trials and Results on IPS-Cell Treatments of Parkinson’s Disease: How Many Patients Have Successfully Been Diagnosed and Are They Safe?

There are more than 60 iPS-cell clinical trials in progress worldwide, nearly one-third of them in Japan. The treatments have shown some benefit and proved to be safe. Technology has been improving at a fast pace. Japan could become the first country in the world to approve iPS-cell-based treatments thanks to a fast-track approvals process. This could happen within a year for Parkinson’s disease.

Results published in March suggest that for three individuals who received the treatment, the cells have survived and are safe one year after surgery2. The signs of benefit are mixed. One of the people said she was able to see her husband for the first time in ten years, but only through a small portion of her eye, where the cells had been replanted.

The trials were only designed to test safety and involve 19 individuals in total, not enough to make a decision about the intervention’s effectiveness.

Some people got better while others didn’t get worse, that’s according to an expert in stem-cell research.

Study of Parkinson’s Disease Using Stem Cells from a Patient Instead of a Donor Emanation: Two Trials in Japan and New Opportunities in Japan

Parkinson’s disease is a brain disease that affects 1 million people in the United States. There are a number of disabling symptoms that can be developed when the dopaminergic neurons die.

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.

In order for 100,000 and 300,000 cells to survive, seven individuals were given a dose of 0.9 million cells and five received a dose of 300,000 cells. A healthy brain typically has 300,000 dopamine-producing neurons. The recipients were given immune-suppressing drugs for one year after the surgery to prevent their bodies from rejecting the transplant.

The results of the scans show an increase in dopamine production, suggesting that some of the cells survived even after the participants stopped taking 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.

A second study by researchers in Kyoto, Japan, uses cells from a patient, instead of an embryo.

Up to 11 million cells were received by four individuals and 150,000 and 300,000 of them 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.

Scientists launched start-up firms. Large pharma companies invested more in manufacturing hubs. Now, medical facilities are preparing to welcome a rush of patients from Japan and abroad. “Regenerative medicine in Japan is moving very dramatically,” says Masayo Takahashi, an ophthalmologist at Kobe City Eye Hospital and president of the biotechnology company, Vision Care. In 2014, she became the first to treat someone with cells derived from iPS cells.

Many countries are looking at ways to market drugs and therapies more quickly. Japan is currently in the spotlight, with a slew of its universities, companies and funding bodies preparing to apply for fast-tracked regulatory approval for certain products based on iPS cells, in some cases perhaps even within the year, as we report in a News Feature.

But those approvals are not yet in hand, treatment costs are high, large trials showing clear clinical benefit have yet to materialize, and concerns about safety could still sap the public’s willingness to try this treatment. We have a lot to realize about the potential of these cells and what the limits are.

Hideyuki Okano, a stem-cell scientist at Keio University in Tokyo, has demonstrated another potential trick for iPS cells. Between 2019 and 2023, he and his colleagues used donor-derived cells to treat four people with spinal-cord injury. The researchers presented preliminary results at a press conference in March, showing that one person with paralysis can now stand and walk. Another can move some of their arm and leg muscles but cannot stand. Two other people did not show any improvement.

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 had limited control over the location of the cells. 2 cm long and 200 micrometres thick were the cells they tried to grow. 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. Cell therapies are time-consuming and expensive to make and the large cell sheets that researchers created for implantation required intrusive surgery. The highest chance of clinical benefit was the main reason for her choosing this approach. It was designed to be “scientifically, the best treatment”.

The problems might be because of the eye’s resistance to regeneration. The eye’s clear covering is maintained by a pool of stem cells and is being rebuilt as part of a cell therapy that could benefit the rest of the eye.

The challenges of obtaining the right conditions for stem-cell research in Japan and the need for more time in the fast-track system: The case of Raymei

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. He says the next clinical trial is crucial.

The regeneration of nerve tissue has been one of the great hopes for iPS cells, but it has been fraught with challenges. Jun Takahashi’s office is lined with statues of elephants and navy-blue samurai armour in order to encourage his lab.

But, unlike his wife, he has not set up a company to develop the technology for manufacturing the cells and conducting the surgery. Instead, he has instead transferred that knowledge to Sumitomo Pharma, based in Osaka. “As a scientist, I am kind of satisfied,” he says. He is now focused on developing cell therapies for stroke.

Similar trials are under way outside Japan, some of which involve many more participants than the Japanese trials. Unlike other areas, Japan’s process of approval for stem-cell research is very easy, says a stem-cell researcher in California. In order for the regenerative-medicine products to be conditionally approved, they have to be shown to have no major safety issues.

Companies can offer the treatments, with costs mostly covered by the national health system. They need to collect data on safety and efficacy in order to get full clinical approval.

One interpretation of this outcome is that the fast-track system’s safeguards are working. There were at least two treatments that needed more time in trials. The failure to achieve the desired level of efficacy meant that patients experienced false hope, and, because treatments granted conditional approval are paid for through Japan’s public health-insurance system, taxpayers were landed with an unnecessary bill.

Takahashi’s robot for macular-degeneration treatments: Early clinical trials reveals improvements in tremors and rigidity

Masayo Takahashi has chosen a more portable manufacturing model for her macular-degeneration treatments: a white, muscular-looking, two-armed robot. Powered by machine learning, it checks in on cells’ progress as they are prepared for transplant through a microscope. It can make enough cells to treat more than 800 people.

There is no cure for diseases that are currently manageable, and two new studies offer hope for people who do. It is important that early-phase clinical trials are part of the regulatory journey. Subsequent trials are designed to assess whether a therapy can benefit patients.

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

“If we’re missing neurons, we’re able to replace them,” Tabar says. “And the full expectation is that these cells are not going to function as cells that just release [a substance like] dopamine. They’re going to rebuild circuitry.”

They are going to stay for a long time. “So you have to check out if there is something else going on or if it is just a bunch of tumors.”

Immature Brain Stem Cells for Transcendental Progenitors to Adhesive Neurosurgers Using Biotechnology and Bayer

The aim is to place these progenitors in places where they will connect with other neurons in the brain.

Another challenge was creating and packaging large numbers of stem cells that could be easily delivered to surgeons. Researchers were able to freeze stem cells until needed.

Studer says that stem cells have the potential to become so many different types of cells, one reason it’s taken so long. It takes the right mix of chemicals to produce a dopaminergic neuron, he says.

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 human stem cells were used in the treatment to make immature brain cells.

According to Dr. Mya Schiess, a neurology professor at UTHealth Houston, the results show that we can stop the disease in its tracks.