Groundbreaking trial of stem cell therapy for Parkinson’s disease

Disease and treatment 20. nov 2022 3 min Associate Professor Agnete Kirkeby Written by Kristian Sjøgren

The Swedish Medical Products Agency has approved the first trial of stem cell therapy for people with Parkinson’s disease. Animal experiments have shown that STEM-PD eliminates motor symptoms completely, and the researchers behind the landmark studies have high hopes that this will also show clinical efficacy in patients.

The Swedish Medical Products Agency has approved a human trial of STEM-PD, a revolutionary stem cell therapy for Parkinson’s disease.

With the approval from the Agency and previous approval from the Swedish Ethical Review Authority, the researchers behind the development of STEM-PD can now initiate the first clinical trial among people with Parkinson’s disease.

STEM-PD is only the third stem cell therapy in the world to be approved for clinical trials among people with Parkinson’s, and the researchers have great expectations that it can put an end to a disease for which there is currently no optimal therapy.

“We have been developing STEM-PD for more than 10 years, and based on experiments in animals, we think that it will also work for people. In the experiments with animals, the treatment reversed Parkinsonian symptoms completely, and our goal is that a single treatment with STEM-PD can relieve Parkinson’s patients from their daily medication,” explains the researcher who has led the preclinical development of STEM-PD, Agnete Kirkeby, Associate Professor, Department of Neuroscience and Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen and Wallenberg Centre for Molecular Medicine, Lund University, Sweden.

No optimal therapy for Parkinson’s

The symptoms of Parkinson’s disease result from the brain’s dopamine-producing cells being destroyed over time.

As the dopamine-producing cells die, the brain cells lose the ability to communicate properly with each other, and this gradually leads to increasingly severe tremors and rigidity.

Parkinson’s is a progressive disease that develops over time, and 10–15 years after diagnosis, virtually no dopamine-producing cells are left in the brain.

There is no optimal therapy to slow down the underlying disease, only symptom-relieving treatments. However, when the dopamine-producing cells are degraded, these drugs gradually lose their beneficial effect and increasingly leave only the side-effects behind.

“We have no therapy to stop cell death or reduce the rate at which the cells die. A new approach to treating people with Parkinson’s is therefore needed,” says Agnete Kirkeby.

Developing embryonic cells

STEM-PD, which Agnete Kirkeby and colleagues have spent more than 10 years developing, does not save the dopamine-producing cells, which are still doomed to die. Instead, the researchers insert new dopamine-producing cells into the brain.

The starting-point for the treatment is embryonic stem cells, which originate from a fertilised human egg from a fertility clinic. These stem cells can become all types of cells, such as kidney cells, brain cells, skin cells and cells in the gut wall. The researchers control the development of these stem cells, so that they develop specifically towards dopamine-producing nerve cells.

The many years of research have been used to identify how gradually exposing stem cells to various growth factors can make them develop step by step from the stem cell stage towards becoming dopamine-producing cells.

When the stem cells in the dish have developed to become immature dopamine-producing cells, they are frozen down, and a neurosurgeon will then carefully transplant the cells into the brains of people with Parkinson’s disease.

“In the brain, the transplanted cells will slowly become fully mature and will begin to communicate with the surrounding cells in the patient’s brain. This is a slow process, and up to 1–3 years can elapse before we see the full beneficial effects of the transplanted cells. In the meantime, we hope that the people with Parkinson’s can gradually be weaned off their daily medication. Even reducing their symptoms by, for example, 70% would be a huge breakthrough,” explains Agnete Kirkeby.

Transplanted into the brain

Agnete Kirkeby explains that STEM-PD has been developed so that it works for everyone – requiring no donor–recipient matching.

In addition, previous experiments with transplanting fetal tissue have indicated that STEM-PD is well tolerated, so that only 12 months of immunosuppressive drugs is needed to prevent the brain from rejecting the new cells.

Eight people with moderate Parkinson’s disease will participate in this first trial of a stem cell therapy developed in Europe.

They will receive STEM-PD by researchers and doctors introducing the cells with needles through the skull and placing them in very specific locations in the brain where the dopamine-producing cells have been destroyed.

“This is a complicated procedure in which the brain is scanned and then the surgeon calculates exactly where the cells should be placed. In this way, we are sure that the transplanted cells have the range to cover the entire area of the brain that is dopamine deficient,” says Agnete Kirkeby.

Third stem cell trial in the world

STEM-PD is the third stem cell therapy in the world in clinical trial for treating Parkinson’s.

Researchers in Japan have developed a similar product and are currently testing it on seven patients. Researchers in the United States have also made a similar product and are studying it with 12 patients. However, neither research group has any results yet.

When the Scandinavian patients have been treated with STEM-PD, the researchers, like their colleagues in Japan and United States, therefore have to wait for the results. Up to 3 years can elapse before the full effects becomes apparent. The waiting time is long because the transplanted cells must mature and establish many communication threads to the patients’ own brain cells through their axons.

Because so much time elapses before any effect becomes apparent, the researchers also select the patients very carefully.

They must have moderate-stage Parkinson’s disease and must not be more than 75 years old.

“Most people with Parkinson’s who are 85 years or older can manage with symptomatic treatment. STEM-PD is therefore primarily intended for people diagnosed early in life and who, without STEM-PD, anticipate living with Parkinson’s for 30–40 years. They end up in a difficult situation 10–15 years after diagnosis when they no longer experience the benefits of the available drugs. We hope that STEM-PD can help these people by weaning them off symptom-relieving medication during the 3 years the transplanted cells take to fully mature,” concludes Agnete Kirkeby.

"Human Embryonic Stem Cell-Derived Dopaminergic Grafts Alleviate L-DOPA Induced Dyskinesia" er udgivet i Journal of Parkinson's Disease. "Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson’s Disease" was published in Cell Stem Cell in 2017. The press release from Lund University can be found here. In 2018, the Novo Nordisk Foundation awarded a grant to Agnete Kirkeby for the projekt ”Mapping human neural lineages in a novel in vitro model of the developing neural tube built with morphogenic gradients”. The STEM-PD trial will include 8 patients from Cambridge (UK) and Lund (Sweden), and the stem cell transplantations will be performed by neurosurgeons at Skåne University Hospital. The STEM-PD trial is further a collaboration between Professor Malin Parmar at Lund University and Professor Roger Barker at Cambridge University, and the project has been developed in a partnership with Novo Nordisk A/S, who also funds the trial.”

The main focus of Agnete Kirkeby’s group is to use human pluripotent stem cells to generate subtype-specific neural cells in 2D and 3D for disease mod...

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