Two stem cell-based therapies for Parkinson's disease demonstrate safety and potential clinical benefits in early clinical trials.

Both therapies use stem cells that have been programmed to develop into dopamine nerve cells, also known as neurons, which produce a chemical called dopamine. Parkinson's disease patients have unusually low levels of dopamine, which helps control body movement, resulting in tremors, slowness of movement and muscle stiffness. In separate clinical trials, the therapies were transplanted into a specific part of a Parkinson's disease patient's brain involved in motor control in order to replace cells that are lost during the course of the disease and to repair the damage caused. Both teams reported that the transplanted cells produced dopamine and the patients reported improvement in their symptoms.

'This is an important milestone on the road towards regenerative brain repair,' said Dr Viviane Tabar, from Memorial Sloan Kettering Cancer Centre (MSK), New York, and first author of the study reporting one of the therapies. 'It represents more than two decades of collaborative work, based on very rigorous science beginning in our labs.'

Researchers at MSK initially developed the first stem cell-based therapy by creating a method to programme human embryonic stem cells to develop into early forms of dopamine-producing neurons (see BioNews 633). Scaling up the process, the researchers have produced large batches of identical cells, which can be frozen and thawed just before surgery.

Results from a phase I clinical trial, published in Nature, detail how surgeons injected either a low or high dose of the therapy into the brains of 12 Parkinson's disease patients. After 18 months, no serious side effects were reported and imaging of the patient's brains showed signs of dopamine cell survival and an increase in dopamine production. Furthermore, some patients reported stabilisation or improvement in their Parkinson's-related symptoms.

The US Food and Drug Administration has granted approval for the therapy to be tested in around 100 patients, in a phase III clinical trial, which is expected to begin this year.

'This is a big step for the stem cell field – to see these encouraging results from a truly off-the-shelf dopamine neuron product in patients with Parkinson's disease,' said Dr Lorenz Studer who was involved in the development of the cells from MSK. 'We are excited to see this move forward into a larger, randomised trial.'

A similar stem cell-based therapy in Sweden, that uses embryonic stem cells as a starting point, has also shown success in early clinical development (see BioNews 1239).

The second stem cell-based therapy was developed by researchers in Kyoto, Japan, with the first patient receiving the therapy in 2018 (see BioNews 975). Results from a phase I/II clinical trial published in Nature, detail how, instead of using embryonic stem cells, the scientists used human pluripotent stem cells from a donor, which were programmed to develop into dopamine neurons.

Surgeons injected a low or high dose of the therapy into the brains of seven Parkinson's disease patients. Similarly to the results of the MSK therapy, after two years, no serious side effects were reported and imaging of the patient's brains showed the transplanted cells had integrated and were producing dopamine. Of the six patients analysed, four reported improvement in motor function after stopping their current medication.

The researchers are seeking conditional approval to sell the allogeneic stem cell-based therapy under a fast-track scheme unique to Japan, in order for larger trials to be conducted to establish efficacy.

Both teams acknowledge that larger trials with more patients and appropriate controls are needed to fully demonstrate the safety and clinical benefits for Parkinson's disease patients.