Background

ANPD001 is a dopaminergic neuron replacement therapy derived from a patient’s own tissue. Fibroblasts from a skin biopsy are converted into pluripotent stem cells and then differentiated into dopaminergic neuron precursor cells. The cells are surgically infused with MRI guidance into the putamen on both sides of the brain, where they are expected to replace dopaminergic neurons that die in Parkinson’s disease. Because the patient’s own cells make up the graft, no immune suppression is needed.

The procedure for producing pluripotent stem cells and neurons was developed at Scripps Research, San Diego, California (Boland et al., 2017). The technology for generating dopaminergic neurons formed the basis for the founding of Aspen Neurosciences in 2018.

In preclinical work, ANPD001cells derived from two Parkinson’s disease patients were transplanted into rats with chemically induced parkinsonism (Hills et al., 2023). Neuron precursors that were differentiated for 18 days, but not 25 days, could relieve motor symptoms. Both types of grafts survived and expressed dopaminergic cell markers, but only the 18-day cells supported robust neurite outgrowth, and thus integration of the cells into the host brain. Gene expression analysis defined a profile associated with efficacy in the model. As presented at meetings, Aspen Neurosciences developed quality control benchmarks based on RNA expression profiling, to guide the selection of cells for transplantation (e.g., June 2022 press release).

A company-sponsored study used non-human primates to optimize the infusion technique (Emborg et al., 2024). Cynomolgus macaques received low-volume intraputaminal injections of 25 to 50 microliters over 10 to 20 minutes, using two needle tracks per side, under MRI guidance. This technique produced accurate placement of cells, which survived out to the last observation at 30 days. The first four animals implanted experienced minor brain swelling and three had transient reduced vision; modifications to surgery subsequently prevented these complications.

Findings

In April 2022, Aspen Neurosciences announced the start of patient screening for a planned Phase 1 trial (press release). The company initiated this trial-ready cohort to identify possible trial participants and begin cell manufacture.

In October 2023, ANPD001 received fast track designation from the FDA (press release).

In January 2024, Phase 1 began with an open-label safety and tolerability trial, making ANPD001 the first autologous cell therapy to enter human testing for Parkinson’s. Nine participants, who will be at least four years past diagnosis and without cognitive impairment, are to receive bilateral cell infusions targeted to the putamen by MRI guidance. Patients will be followed for five years post-transplantation, to assess adverse events, and effects on Parkinson’s symptoms. Cell survival will be measured by 18F-DOPA PET. After that, telephone follow-up will assess safety and tolerability for an additional 10 years. The study is enrolling by invitation at seven sites in the U.S., and is funded by the California Institute for Regenerative Medicine (press release).

On January 13, 2025, the company announced the completion of dose escalation and the first two cohorts in the trial. They reported no serious adverse events. The trial will proceed to test their commercial formulation (press release).

In an independent effort, researchers at McLean Hospital in Boston reported transplantation of patient-specific dopaminergic neuron progenitor cells in one person with Parkinson’s disease. The cells survived without the need for immunosuppression. Clinical symptoms stabilized or improved 18 to 24 months after implantation (Schweitzer et al., 2020). In August 2024, this group began a single-center Phase 1 safety trial in six patients, funded by the NIH and Oryon Cell Therapies. The study will deliver cells to the putamen on one side of the brain, and assess adverse events for 18 months after surgery.

For details on the ANPD001 trial, see clinicaltrials.gov.