Malin Parmar’s early interest in how cells form and what controls cell identity led her to pursue a PhD focused on forebrain development. During her first postdoctoral research she shifted focus to midbrain development, particularly studying dopamine neurons, which are crucial for understanding and developing cell therapies for Parkinson’s disease. Around this time, advances in human embryonic stem cells and later, induced pluripotent stem cells (iPSCs), made it possible to envision medical therapies based on stem cell differentiation. Parmar learned how to culture human embryonic stem cells, which led her to pursue developing a stem cell therapy for Parkinson’s disease.

For me, it’s been a progressive development from an interest in very basic science to translational science. It’s been very rewarding to follow the trajectory of development from something you do in the research lab until the day you can deliver it to a patient.

“For me, it’s been a progressive development from an interest in very basic science to translational science. It’s been very rewarding to follow the trajectory of development from something you do in the research lab until the day you can deliver it to a patient,” she states.

Stem cell derived dopamine neurons grown in culture. Photo: Agnete Kirkeby

From research to reality 

More than ten years ago, Parmar and her team uncovered the initial experimental findings in stem-cell-based transplants in Parkinson’s disease (STEM-PD): how to generate dopamine neurons from human embryonic stem cells, aiming to use them for treating Parkinson’s disease. From 2012 to 2018, they validated the cells, focusing on their safety, efficacy, and suitability for patient use. Six years ago they began targeting clinical applications, supported by the promising pre-clinical data, started to produce the cells under Good Manufacturing Practice (GMP) standards, and completed the necessary safety and efficacy testing for regulatory approval.

In February 2023, transplants were carried out on the first patient at Skåne University Hospital in Lund, Sweden. The study involves dosing four patients initially, followed by a waiting period to assess safety before administering a higher second dose, which was initiated in May this year. 

It takes about six to twelve months for the cells to start to mature and function after transplantation, and then they will continuously increase in the maturation of functionality over a couple of years when the cells are expected to produce dopamine and have a therapeutic effect in the patients.

“However, we still need more time to determine whether the cells are effective and provide the therapeutic benefits we are hoping for,” Parmar says. “The primary goal is to assess safety and tolerability, with a secondary focus on cell survival and efficacy.” 

“It takes about six to twelve months for the cells to start to mature and function after transplantation, and then they will continuously increase in the maturation of functionality over a couple of years when the cells are expected to produce dopamine and have a therapeutic effect in the patients. Therefore, data on the effectiveness of the cells will be evaluated three years after the patients have received transplants,” Parmar explains. 

Section of rat brains transplanted with human dopamine neurons being prepared for analysis in the lab of Malin Parmar. Photo: Kennet Ruona.

A major undertaking 

Parmar emphasizes that making this treatment routinely available in clinics will be a monumental task. As the first human dose trial, this academic study involves eight patients receiving two different doses. To advance this work further, they have now partnered with Novo Nordisk, which will continue developing global stem-cell therapy for Parkinson’s disease through its ‘Transcend’ program.

“It’s been a tremendous effort, with a large team collaborating primarily between Lund and Cambridge, alongside other European partners, working for years to advance this from research to clinical trial and a potential therapy,” Parmar states. 

She remarks that starting this first human trial has not been an easy process. They have encountered many challenges in getting regulatory approval for the product and also other regulatory procedures due to Brexit in the UK. 

“Brexit complicated our process since our cells were produced in the UK, but the transplants were in Sweden, part of the EU. We had to navigate complex regulations and secure approvals from both Swedish and UK authorities due to having patients in both regions,” Parmar says. 

Next steps 

Parkinson’s disease is highly variable, with some patients diagnosed early and requiring cell transplants by their 40s or 50s. For these patients, the transplanted cells must remain healthy in the brain for decades. 

“During the next decade, I hope we see multiple cell-therapy products become available, allowing patients to choose the best option based on their disease type and stage. Additionally, I aim for our second-generation cells to advance to clinical trials, leading to improved cells, grafts, and therapies,” Parmar says. 

It’s incredibly exciting that several stem-cell-based trials are currently underway.

She also outlines that future treatments may involve personalized cell therapies using the patient’s cells or hypoimmune cells, which reduce the need for immune suppression. These advances will also focus on optimizing cell delivery methods and dosages.

“It’s incredibly exciting that several stem-cell-based trials are currently underway. There’s our trial in Europe, along with two in the US and one in Japan. We’re at a thrilling stage in the field, but this is just the beginning. It means we’re poised to develop better cells and more effective therapies,” concludes Malin Parmar. 

About the author

Paula Pérez González-Anguiano, M.Sc. in Scientific, Medical and Environmental Communication, is a Science Journalist and Illustrator based in Barcelona, Spain.