Background

This cell-based therapy consists of a neuron graft for the treatment of Parkinson’s disease. The grafting cells are derived from human embryonic pluripotent stem cells, and converted in the lab to dopamine-producing neuron progenitors. They are surgically implanted into the putamen. 

The protocol for differentiating stem cells to MSK-DA01 originated at Memorial Sloan Kettering Cancer Center (Kim et al., 2021). The same group generated large quantities of clinical-grade, frozen cells for preclinical and toxicology testing. In immunodeficient rats lesioned with 6-hydroxydopamine to mimic Parkinson’s disease, the cells rescued motor deficits. Postmortem examination of treated rats found large, well-differentiated human dopamine neurons in the striatum. Toxicology studies in immunocompetent mice noted no obvious adverse effects. None of the injected cells were detected outside the brain, and no overgrowth or tumor formation was observed (Piao et al., 2021).

A similar effort to develop stem cell-derived dopaminergic grafts is ongoing in Kyoto, Japan (see Takahashi, 2020).

Findings

In May 2021, BlueRock Therapeutics, a subsidiary of Bayer, began a Phase 1 safety study. Twelve people who have had Parkinson’s disease for five to 15 years, and still respond to levodopa, had a one-time surgical implantation of cells in their putamen bilaterally. Five people received 0.9 million cells per putamen, and seven got 2.7 million. All took immunosuppressants for one year. Primary outcomes were serious adverse events and signs of abnormal overgrowth of transplanted cells during the first year. Secondary outcomes include evidence of cell survival by 18F-dopamine PET scan, PD symptoms, and safety after two years. The trial, at two sites in the U.S. and one in Canada, finished the one-year follow-up in May 2023. The treatment met safety goals, according to data presented in August 2023 at the International Congress of Parkinson’s Disease and Movement Disorders in Copenhagen, Denmark (press release). No serious adverse events related to the implant were reported after one year. A seizure in one patient was attributed to the surgical procedure, and resolved fully. PET imaging demonstrated evidence of cell survival and engraftment in both low- and high-dose cohorts. Patients improved on secondary endpoints measuring motor symptoms using the MDS-Unified Parkinson’s Disease Rating Scale Part III and the Hauser Diary, with greater benefits observed in the higher dose cohort. At 18 months, the therapy continued to be safe, according to presentations at the March 2024 AD/PD conference. At this time, immunosuppression had been stopped for six months. There were no deaths or discontinuations, or graft-induced dyskinesias. Clinical scores remained stable or trended toward improvement. On PET imaging, 18F-dopamine uptake in the transplanted region was increased compared to baseline, and increased or stable compared to one year. Uptake in the caudate, a non-transplanted region, was lower than baseline. MRI revealed no evidence of intracerebral hemorrhage, cellular overgrowth, or tumor formation. This trial will continue to evaluate patients for up to five years. 

In July 2021, the U.S. FDA granted fast-track status to DA01 for treatment of advanced Parkinson's.

In July 2022, BlueRock began a large, non-interventional study evaluating the variability, reliability, and compliance of self-reporting using the PD Diary to assess motor symptoms. The study, enrolling 400 patients in the U.S., Canada, and Europe, will run until 2025.

In October 2023, Bayer announced the opening of a new cell therapy production plant in California to produce material for additional clinical trials of BRT-DA01 (press release).

A Phase 2 trial is expected to start in late 2024 (Bayer press release).

For details on these trials, see clinicaltrials.gov.