Cell-therapy for Parkinson’s disease: a systematic review and meta-analysis

Abstract

Background Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson’s disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients. Methods We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects. Results The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the ‘off’ state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6–100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the ‘off’ state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis. Conclusions This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760

Efficacy and efficacy-influencing factors of stem cell transplantation on patients with Parkinson’s disease: a systematic review and meta-analysis

“…A different work also yields a similar conclusion. Cell therapy, according to Wang and colleagues, at least decreased UPDRS scores in the 12-month follow-up group (33). Similar findings imply that most transplanted cells have a maximum survival period of 12 months.…”

Some Novel Therapies in Parkinson’s Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature

“…Cell-based therapies for PD are aimed at replacing the lost or damaged dopaminergic neurons in the brain, restoring the balance of neurotransmitters, and ultimately improving motor function and reducing symptoms [ 8 ]. Several types of cell-based approaches have been explored in preclinical and clinical studies, including fetal tissue transplantation, stem cell transplantation, and iPSC therapy [ 52 ] ( Figure 2 Shows the key cell types).…”

“…Further research and development efforts are needed to optimize gene delivery, enhance long-term safety and efficacy, and explore emerging gene editing technologies. PD-related celltherapies are not independent therapies but should always be advised together with validate regimens [ 8 ]. By leveraging cutting-edge nanotechnologies and innovative approaches, researchers are making strides towards the development of new treatments that could offer new hope and improved outcomes for patients with PD.…”

“…While traditional therapies have been the mainstay of PD treatment for many years, new and more effective treatment options are required for PD patients [6]. In recent years, novel therapies for PD have encompassed a wide range of approaches, including gene therapy, cell-based therapies, targeted drug delivery, neuroprotective agents, and magnetic field therapy [7][8][9][10][11][12]. The goal of these novel therapies is to alleviate the symptoms of PD as well as to downturn or suspend the PD course itself.…”

Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges

“…Monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyl-transferase (COMT) inhibitors, and deep brain stimulation therapy are also widely used, but these treatments cannot stop the progression of the disease either [3]. Even in cell transplantation therapy, Lewy bodies have also been reported to appear in grafts, and the value of the therapy remains to be seen [4][5][6].…”