Dopaminergic Progenitor Cell Therapy Shows Some Symptom Improvement in Parkinson Disease

Prof. Dong-Wook Kim

Credit: S.BIOMEDICS

TED-A9 cell therapy has demonstrated safety with some preclinical efficacy in the first 4 participants with Parkinson disease (PD) treated in a phase 1/2 clinical trial conducted at Severance Hospital of Yonsei University in South Korea led by Professor Jin-Woo Chang, a neurosurgeon and Professor Phil Hyu Lee, a neurologist.¹

“Although this clinical evaluation only targets the first 3 low-dose patients, but not all 12 subjects, no adverse issues related to transplant surgery or cell safety were observed in one-year post transplantation. Importantly, the clinical results demonstrated very promising efficacy,” Prof. Dong-Wook Kim, Yonsei University College of Medicine and CTO, S.BIOMEDICS, said in a statement.¹ “The results are believed to align closely with the findings from our preclinical in vitro and in vivo studies. We are excited that TED-A9 could be a fundamental treatment that directly replaces dopaminergic neurons lost in patients with PD.”

TED-A9 is a hESC (human embryonic stem cell)-derived midbrain dopaminergic progenitor cell therapy surgically transplanted to the anterior, middle, and posterior sections of the putamen, with 3 tracks per each putamen. The transplanted cells are then expected to mature into dopaminergic neurons and restore dopamine production and motor function.

The phase 1/2 trial is being conducted in 12 participants with PD, diagnosed for more than 5 years and exhibiting motor complications such as wearing-off, freezing of gait or dyskinesia. Participants are aged between 50 and 75 years old. Six participants have been treated in the low-dose group (3.15 million cells) and 6 participants have been treated in the high-dose group (6.30 million cells). The final participant was treated in February 2024.¹

In the first 3 participants in the study, at 1 year post-transplant, DAT brain imaging (FP-CIT-PET) revealed an increase in dopamine transporters (DAT), suggesting potential dopamine neuron engraftment. This increase correlated with improvements in PD symptoms.¹

Investigators observed no adverse events effects related to the cell transplantation or surgery on MRI and CT scans 1 year after treatment. On Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III [off] evaluation), the participants had a mean decrease of 12.7 points from baseline (61.7 to 49.0) at 1-year post treatment. Improvements were also observed in wearing off and freezing of gait symptoms. Data from the higher dose cohort will be shared in Fall 2024 when those participants have reached 1 year of follow-up.¹

Another recent novel therapy that has made headway in PD is Asklepios Biopharmaceutical’s AAV2-GDNF gene therapy (AB-1005), a phase 1b clinical trial (NCT04167540) of which recently met its primary safety and efficacy endpoints at 18 months, showing stability in disease markers in participants with mild to moderate PD.²

AB-1005 is an investigational adeno-associated virus (AAV2) gene therapy containing the human glial cell line-derived neurotrophic factor (GDNF) transgene.

In 6 participants with mild PD, there was relative stability from baseline to 18 on Activities of Daily Living scores and Motor Examination scores in “ON” and “OFF” medication states on MDS-UPDRS. The moderate cohort had a mean improvement of 3.8 (standard error [SE], 3.5) on Activities of Daily Living from baseline and of 20.4 points (SE, 4.5) “OFF” medication and 10.6 points (SE, 3.6) “ON” medication compared to baseline.²

“These early findings are encouraging and show AB-1005 to be well tolerated in this study in patients with mild to moderate Parkinson’s disease,” Krystof Bankiewicz, MD, PhD, Scientific Chair, Parkinson’s and MSA, AskBio, said in a statement in May 2024.² “Further, they highlight areas of potential future exploration in our upcoming Phase II REGENERATE PD trial, which will look more closely at the potential efficacy of AB-1005 in the treatment of Parkinson’s disease.”

REFERENCES
1. S.BIOMEDICS Dopamine Cell Therapy for Parkinson’s Disease with TED-A9 Shows Promising Results at 12 months in Phase I/IIa Clinical Trial. News release. S.BIOMEDICS. July 9, 2024. https://www.businesswire.com/news/home/20240709317387/en/
2. Van Laar AD, Christine CW, Merola A, et al. Phase 1b Safety and Preliminary Efficacy of Bilateral Intraputaminal Delivery of AAV2-GDNF (AB-1005) in Participants With Mild or Moderate Parkinson’s Disease​. Presented at: 2024 AAN Annual Meeting, April 13-18; Denver, Colorado.