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Clinical trials assessing cell therapies for Parkinson disease treatment may show early potential in improving both motor and nonmotor symptoms.
Claire Henchcliffe, MD
(Credit: Weill Cornell Medicine)
According to a recent report from GlobalData, using data from BlueRock Therapeutics’ phase 1 study (NTC04802733) assessing bemdaneprocel, an investigational allogenic stem cell derived cell therapy, and other clinical trials for Parkinson Disease (PD), findings suggest that cell therapies in development may address the motor and non-motor symptoms of patients with PD with minimal adverse effects.1
BlueRock Therapeutics recently presented positive 18-month data on bemdaneprocel from the phase 1 study at the 2024 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD), held March 5-9, in Lisbon, Portugal. Conducted by lead author Claire Henchcliffe, MD, chair of the Department of Neurology, UCI School of Medicine, University of Califorina, Irvine, and colleagues, the results showed that the agent was safe and well tolerated, with treated patients demonstrating improvements in ON and OFF time over that time.2
"My initial reaction is that the results are encouraging, however as a Phase I study which was not powered to measure statistical significance against a control group, bemdaneprocel true clinical potential is likely to be demonstrated in future later phase trials,” Lorraine Palmer, PhD, pharma analyst at GlobalData, told NeurologyLive®. "The results from the phase 1 study do not have significant implications for patients with PD at the moment due to the early stage of bemdaneprocel. The present results suggest survivability of the transplanted cells and an improvement in both motor and non-motor symptoms. However, conclusions cannot be drawn until further trials are carried out."
READ MORE: Dosing Underway for Phase 1/2a Study of Autologous Cell Therapy ANPD001 in Parkinson Disease
The multicenter, open-label, non-randomized, non-controlled trial had 12 patients with PD who received surgical transplantation of 1 of 2 different dose levels of bemdaneprocel cells to the post-commissural putamen bilaterally, along with an immunosuppression regimen for 1 year. Using the Hauser Diary, those in the high-dose cohort demonstrated a mean increase of 2.7 hours in good ON time compared with baseline following 18 months of treatment. Additionally, this patient group treated demonstrated a mean reduction of 2.7 hours in time spent in OFF state.
In the 2 cohorts, patients on high-dose bemdaneprocel (n = 7) had a dose of 2.7 million cells per putamen whereas those in the low-dose group (n = 5) had a dose of 0.9 million cells per putamen. The initial 12-month data of the trial, presented at the 2023 International Congress of Parkinson’s Disease and Movement Disorders, held August 27-31, in Copenhagen, Denmark, highlighted the efficacy and safety of this treatment. At 1 year, the participants in the high-dose cohort displayed a reduction of 13.0 points in MDS-UPDRS-III scores compared with the baseline.
Additional findings were less pronounced in the low-dose cohort, with reductions of 7.6 points after 1 year. Imaging analysis using 18F-DOPA PET, a technique used to visualize and assess dopaminergic activity, revealed evidence of cell survival and engraftment in both the high and low dose cohorts. At 1-year follow-up investigators observed no reports of no serious adverse events (AEs) attributable to bemdaneprocel; however, they did note 2 unrelated serious AEs of seizure attributed to the surgical procedure and 1 COVID case where both resolved without sequelae.
"The current medications used for the treatment of PD are limited to those providing symptomatic relief of motor symptoms, leaving ample opportunities for new entrants into the PD market," Palmer said. "The need for disease-modifying therapies that can slow or modify the disease course is one of the highest unmet needs and was consistently highlighted in KOL discussions with GlobalData."
Lorraine Palmer, PhD
(Credit: GlobalData)
Global Drug Database highlighted 2 other neuronal progenitor stem cell therapies that have completed phase 1 or above trials in PD and disclosed results.1 These other therapies include ISC-hpNSC (Cyto Therapeutics) and HSCfPD (Celavie Biosciences). Similar to the trial assessing bemdaneprocel, Cyto Therapeutics reported improvement in non-motor symptoms in their phase 1/2a trial (NCT02452723) with ISC-hpNSC. In addition, Celavie Biosciences noted minor improvements in non-motor symptoms in their phase I trial (NCT02780895) with HSCfPD. "It is worth noting that the highest stage of development for PD cell therapies undertaken so far is phase 2a. So while they show promise, it is still too early stage for any firm conclusions to be drawn," Palmer said.
There are 5 other neuronal progenitor stem cell therapies being investigated in phase 2 and phase 2 trial for PD, all currently have no published results. It was noted in the report that only 2 companies have disclosed estimated publication dates for their trial data: NN-9001 (Novo Nodisk AS) in 2025 and TED-A9 (S.Biomedics) in 2026. "Therefore, the next few years will be crucial in determining the full potential of neuronal stem cell therapies for the treatment of PD, including replacing lost dopaminergic neurons and the treatment of non-motor symptoms," Palmer added.
In February 2024, S.Biomedics announced successful completion of the brain transplant of cell therapy TED-A9 for their phase 1/2a study in treating PD.3 The trial was conducted on 12 patients, between the ages of 50 and 75 years, diagnosed with PD for over 5 years and showed motor complications such as drug wearing-off, freezing of gait or dyskinesia. In the study, TED-A9 were administered to 6 patients in the low-dose group (3.15 million cells) and to another 6 patients in the high-dose group (6.30 million cells).
Initially, a cohort of 3 patients were enrolled at a low dose to investigate the original safety of TED-A9, including dose-limiting toxicity evaluation, up to 3 months post-transplantation. In this time frame, investigators observed no reports of safety concerns and because of this, an additional 3 patients were enrolled at a high dose for evaluation over another 3 months post-transplantation. Since there continued to be no safety issues reported in the extended period, the trial added another 3 patients to each of the low-dose and high-dose groups, totaling 12 patients. Overall, none of the 12 participants had any adverse events, complications, or unusual adverse reactions following the transplantation of TED-A9.
"PD is characterized by progressive degeneration of the neurons of the substantia nigra pars compacta, which reduces the levels of dopamine available for neurotransmission in the corpus striatum. As such, cell therapies could have the potential to replace the loss of dopaminergic neurons in PD patients," Palmer said. "Early clinical trials of stem cell transplantation in idiopathic PD patients have shown a reduction in motor symptoms and non-motor symptoms. However, the sample size of these clinical trials have been small and were not powered to measure statistical significance. Moving forward, large scale pivotal trials are required to investigate the efficacy of stem cell therapy on functional improvement (including the assessment of motor and non-motor PD symptoms), the safety profile, and the ability of stem cells to restore dopaminergic neurons in patients with PD ."
