The stem cell race for Parkinson’s disease: Recent studies show significant promise

Parkinson’s disease is an extremely complex condition to treat. Although there are medications available that can help relieve symptoms, there are still no approved therapies that slow down the progression of the underlying disease. But the biotech industry has not given up on finding new types of treatments that could potentially change the outcome for people suffering from the debilitating condition, and recent news of positive early-stage results for stem cell therapies has produced new hope for Parkinson’s patients.

What are the causes of Parkinson’s disease and current therapeutic approaches?

Although the underlying cause of Parkinson’s is unknown, scientists do know that the disease results from a loss of neurons in the substantia nigra region of the brain that make the chemical dopamine, which plays a crucial role in the brain’s reward system, influencing feelings of pleasure, motivation, and movement, as well as impacting mood, attention, learning, and memory. The loss of these neurons subsequently causes dopamine levels to plummet, which is ultimately the driving force behind why patients eventually experience such troublesome symptoms – these generally occur when around 80% of neurons have failed.

Right now, the main treatment for Parkinson’s aims to increase the levels of dopamine in the brain. The drug levodopa is considered to be the most effective option, and is often combined with other medications to enhance its effectiveness and reduce side effects. However, not all patients respond to these drugs, and in some cases, doctors even perform surgery to run electrodes deep into the brain to help alleviate tremors and other symptoms.

How can stem cell therapy treat Parkinson’s?

But what if Parkinson’s could be treated directly at its source by actually restoring the lost neurons?

That is exactly what stem cell therapies aim to do. Stem cells have the potential to develop into any kind of cell found in the body, including brain cells, and researchers are now able to turn stem cells into dopamine-producing nerve cells. Essentially, this means that stem cells can be implanted into the brain to take the place of the cells that have been lost – a potentially transformative treatment approach for Parkinson’s. 

Although the idea behind replacing the neurons killed off by Parkinson’s is not new, it is only now just starting to produce some success. In the 1980s, researchers started to experiment with the transplantation of fetal tissue into Parkinson’s patients, but the results were uneven, and some troubling side effects like uncontrolled movement occurred. 

It was not long after this that stem cells came into the picture. But while they promised better results, the technology evolved slowly, taking a long time to advance to where it is now. In an interview with NPR, Dr. Lorenz Studer, who directs the Center for Stem Cell Biology at the Sloan Kettering Institute in New York, said that one of the reasons for this is that, because stem cells have the potential to become so many different kinds of cells, it takes just the right mix of chemicals at just the right time to produce a neuron that makes dopamine. Additionally, creating and packaging large numbers of stem cells that could be easily delivered to surgeons was also a challenge – that is, until researchers developed techniques that allowed them to freeze stem cells.

Now that many of these technical hurdles have been overcome, stem cells may finally be poised to fulfill their true potential in Parkinson’s treatment. 

Progress made in clinical trials: Recent stem cell therapy studies show significant promise for Parkinson’s treatment 

Indeed, a couple of recent early-stage clinical trials from BlueRock Therapeutics and Kyoto University have helped to back up this notion. 

BlueRock Therapeutics accelerates Parkinson’s stem cell therapy bemdaneprocel into phase 3 trials 

BlueRock Therapeutics, a subsidiary of biotech and pharma giant Bayer, is currently leading the way in the field as it smoothly advances its stem cell therapy for Parkinson’s, called bemdaneprocel, into phase 3 trials after receiving the all clear from the U.S. Food and Drug Administration (FDA) to progress the candidate in January 2025. 

This came after the candidate, which is made up of immature brain cells called dopaminergic neuron progenitor cells that are derived from human embryonic stem cells, produced positive results in a small phase 1 study involving 12 people with Parkinson’s in the U.S. and Canada. 

The participants received either a low or high dose of bemdaneprocel via an injection into a structure of the brain that is involved in learning and motor control. PET scans taken 18 months after the procedure showed that the transplanted cells were producing dopamine, and an assessment using a standard rating scale of Parkinson’s progression suggested the treatment was also easing symptoms. Ultimately, the trial met its primary endpoint of tolerability and secondary endpoints on motor impairments at 24 months post-surgery.

When announcing that the FDA had given it the go-ahead to take bemdaneprocel into phase 3 of development, BlueRock stated that it expects to begin its phase 3 registrational trial of bemdaneprocel at some point in the first half of 2025, meaning it should not be long now before we hear news of this. 

Kyoto University demonstrates the promise of induced pluripotent stem cell therapy for Parkinson’s

Meanwhile, a phase 1/2 trial conducted by Kyoto University Hospital and the Center for iPS Cell Research and Application (CiRA) in Japan has recently produced positive results for its own dopaminergic progenitor cells. In this instance, the cells were derived from induced pluripotent stem cells rather than from embryonic stem cells like BlueRock’s candidate. The results, however, were very similar. 

In the study, seven male and female patients, aged between 50 and 69, each received transplants of the dopaminergic progenitor cells into both sides of their brains. Throughout the two-year monitoring period, there were no reports of severe adverse reactions, although there were some mild to moderate events such as itching at the injection site and an instance of transient dyskinesia, a movement disorder that usually develops as a result of certain medications. 

The results also showed that dopamine production increased, based on a 44.7% rise in 18F-DOPA uptake in the putamen, especially in the high-dose group. And, even more encouragingly, four out of six participants reported a 20% improvement in motor scores off medication, and there was an average improvement of 4.3 points on medication, suggesting that the grafted cells had integrated into the brain’s circuitry and were functioning as a new source of dopamine.

The Japanese drug firm Sumitomo Pharma cooperated with Kyoto University’s trial, and it now has plans to apply to the government for permission to commercially produce the cells.

It is worth noting that Japan has been pioneering stem cell research over the past couple of decades, building on the Nobel-prize-winning work of Shinya Yamanaka, who discovered in 2006 that adult cells could be reprogrammed into an embryonic-like state, capable of becoming almost any kind of tissue. Since then, the Japanese government has poured more than 110 billion Japanese yen ($770 million) into research and development on regenerative medicine, while billions more has been added from private investors and companies. 

With the recent success of early-stage stem cell trials in the country, including Kyoto University’s phase 1/2 study for Parkinson’s, Japan’s big bet on stem cell research might just be about to pay dividends. 

New technologies related to stem cells for Parkinson’s disease

• Brain Organoid Platform for Parkinson’s Disease Drug Discovery – Okinawa Institute of Science and Technology
• Midbrain‐Microglia Assembloids – Research Luxembourg
• A Method to Generate Microglia from Human Pluripotent Stem Cells – Whitehead Institute

A “big leap” in Parkinson’s treatment 

Parkinson’s is the second-most common neurodegenerative disorder after Alzheimer’s disease, with incidence rates increasing year on year. A study conducted in 2022 revealed that nearly 90,000 people are diagnosed with Parkinson’s disease in the U.S. each year, representing a steep increase from the previously estimated rate of 60,000 diagnoses annually.

In fact, the number of people diagnosed with Parkinson’s in the U.S. is expected to double by 2040. Given the alarming rise in incidence rates, if there were ever a time to come up with a breakthrough treatment for Parkinson’s, it would be now. Fortunately, stem cell therapy has been acknowledged as a “big leap” for the indication and could potentially serve as the much-needed breakthrough treatment, as long as it continues to show success in late-stage trials. 

But there is still a long way to go in the field. Dr. Mya Schiess, a neurology professor at UTHealth Houston, recently told NPR that there may still be risks with stem cell therapies, meaning that scientists will need to continue to monitor the stem cells that were transplanted into patients’ brains during the aforementioned trials. She also noted that stem cells do not cure an underlying disease like Parkinson’s, so there is a possibility that the new neurons may eventually succumb to the same disease process after a certain amount of time passes.

Nevertheless, it goes one step further than current treatments, as it could still offer potential for stopping progression and bringing about improvement in motor function, and is perhaps the best solution for a disease that scientists still do not fully understand in terms of its underlying pathology.  

Although the trials mentioned in this article were only small and were intended to show safety, the clinical improvement that was also witnessed is already extremely promising. And, even though there is not yet a vast array of clinical trials taking place in this area, BlueRock Therapeutics’ and Kyoto University’s positive data could pave the way for more companies to enter a therapeutic field that could change the outcomes for patients with Parkinson’s like never before.