Investigational Agent ANPD001 Demonstrates Preclinical Safety and Efficacy for Parkinson Disease Treatment
ANPD001, an autologous cell therapy derived from patient-derived iPSCs, is designed to replace lost dopamine neurons in patients with Parkinson disease.
Andrés Bratt-Leal, PhD
In recent preclinical data findings investigating ANPD001 (Aspen Neuroscience) for the treatment of Parkinson Disease (PD), the investigational agent demonstrated safety and efficacy in the ability to manufacture patient specific dopamine neuron precursor cells (DANPCs), thus supporting further clinical investigation.1 Following treatment, the researchers observed no migration or tumor formation, suggesting that the PD neurons function in vitro and restore dopamine signaling deficits in the animal models.
Presented at the 2023 World Parkinson Congress, held July 4-7, in Barcelona, Spain, the DANPCs were created from 6 different skin biopsies, which were donated by patients diagnosed with PD. Then, multiple induced pluripotent stem cell (iPSC) clones were produced and identified from the donors individually. The autologous iPSCs were then distinguished into DANPCs, which were then assessed for efficacy in a well-known animal model of PD.
"At the time of PD diagnosis, it is estimated that, for many patients, most of their dopaminergic neurons in the substantia nigra and their projections in the putamen are lost, resulting in the motor symptoms of the disease," senior author Andrés Bratt-Leal, PhD, senior vice president R&D and cofounder of Aspen Neuroscience, said in a statement.1 "Aspen is very encouraged by the results of these studies, which demonstrate the ability to manufacture and produce personalized, patient specific DANPCs in support of a future clinical study."
Safety, biodistribution, and tumorigencity of the DANPCs were characterized in intact immunodeficient Rowett nude rats under Good Laboratory Practices (GLP). In the study, 4 lines were tested for efficacy in a 6-OHDA medial forebrain bundle lesion rodent model of PD, with histological examinations to determine survival, phenotype, and innervation of the resulting grafts.
“At the time of diagnosis, it is estimated that a PD patient has already lost the majority of dopaminergic neurons in the substantia nigra and their projections in the putamen, a major contributing feature to the motor symptoms of the disease. There is a well-established history that replacement of the missing dopamine through transplantation of dopaminergic neurons into the putamen has the potential to improve motor function and reduce Parkinson medication intake,” Bratt-Leal et al wrote.2
ANPD001, an autologous cell therapy derived from patient-derived iPSCs, is designed to replace lost dopamine neurons in patients with PD. In its production, the company has imitated the manufacturing process for the generation of high-quality neurons from patient donors. Under the conditions of good manufacturing practice, the whole genome sequencing at each stage warrants that genomic mutations are not present in the cells selected. The company uses RNAseq for the prediction of downstream functionality of both the iPSCs and the DANPC.
“The technology now exists for ex vivo generation of patient-specific dopaminergic neurons by reprogramming somatic cells into iPSCs and then further differentiating iPSCs to DANPCs and neurons. Autologous cell therapy has the potential advantage of not requiring immune suppression, which is costly and may not be well tolerated in older populations,” Bratt-Leal et al noted.2
PD is the second most common neurodegenerative disease, impacting more than 10 million patients globally, and currently does not have an approved disease-modifying treatment for patients. In a statement, it was noted that one of the potential advantages of ANPD001 as a treatment for PD is that it will not require immunosuppressive drugs, which may not be well tolerated in some patient populations.1
Bratt-Leal and colleagues noted, “Towards development of an autologous neuron replacement therapy, Aspen Neuroscience has established the manufacturing process to produce DANPCs from PD donor iPSCs under GMP conditions and characterize these cells using a battery of quality control assays. We have generated large reference data sets for developing predictive genomic assays, not only to assess the genome integrity of each lot of cells, but also to predict their ability to form functional dopaminergic neurons.”2
