Archive for June 2025
Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease
Parkinson’s disease is a progressive neurodegenerative condition with a considerable health and economic burden1. It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses. Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational cryopreserved, off-the-shelf dopaminergic neuron progenitor cell product (bemdaneprocel) derived from human embryonic stem (hES) cells and grafted bilaterally into the putamen of patients with Parkinson’s disease. Twelve patients were enrolled sequentially in two cohorts—a low-dose (0.9 million cells, n = 5) and a high-dose (2.7 million cells, n = 7) cohort—and all of the participants received one year of immunosuppression. The trial achieved its primary objectives of safety and tolerability one year after transplantation, with no adverse events related to the cell product. At 18 months after grafting, putaminal 18Fluoro-DOPA positron emission tomography uptake increased, indicating graft survival. Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort. There were no graft-induced dyskinesias. These data demonstrate safety and support future definitive clinical studies.
Repeated Intravenous Administration of Mesenchymal Stromal Cells Produces Cumulative Beneficial Effects in Chronic Ischemic Cardiomyopathy
Cell therapy is a potentially useful approach to treating heart failure (HF) secondary to chronic ischemic cardiomyopathy (ischemic HF). Despite controversy, the preclinical data in the field of cell therapy are clear: Although transplanted cells do not regenerate cardiomyocytes, preclinical studies have consistently shown that they improve cardiac performance. Bone marrow–derived mesenchymal stromal cells (MSCs) are among the most promising cell types in the preclinical arena1 and for patients with ischemic HF.
The field of cell therapy is evolving rapidly. The fundamental shift has been the recognition that all cell types fail to engraft in the heart and instead work via paracrine mechanisms. This concept has 2 corollaries: (1) because transplanted cells do not persist in the heart for more than a few weeks, giving repeated doses seems logical; and (2) because cells work by releasing factors in the environment, intravenous (IV) therapy may also be effective by enabling systemic release of these factors.