Dosing Underway for Phase 1/2a Study of Autologous Cell Therapy ANPD001 in Parkinson Disease

Paul Larsen, MD, FAANS

Aspen Neuroscience recently announced initial patient dosing in its phase 1/2a ASPIRO trial (NCT0634406) assessing the safety and tolerability of ANPD001, an autologous, dopaminergic neuron cell replacement therapy in development for patients with moderate to severe Parkinson disease (PD).¹

ASPIRO, an open-label study, will include patients aged 50 to 70 years old with moderate to severe PD and excludes those with cognitive impairment and other comorbidities that could preclude treatment. The trial will primarily assess safety and tolerability of ANPD001, with other secondary end points that include changes in ON time, experiences of good symptom control, and improvements in motor symptoms and quality of life based on standard PD rating scales.

The first transplantation procedure of the neuronal replacement therapy was performed at Banner – University Medical Center Tucson, the lead dosing site for ASPIRO. Paul Larsen, MD, FAANS, a professor of neurosurgery at the University of Arizona College of Medicine–Tucson, is the lead neurosurgeon, with years of experience in MRI-guided stereotaxy. His clinical research team has several years of experience, participating as the solo or lead group in 12 cell and gene therapy clinical research trials since 2004.

"Parkinson's disease is the most common neurodegenerative movement disorder, primarily affecting the depletion of dopamine neurons in the midbrain. By the time of diagnosis, it is common for people with Parkinson's to have lost the majority of dopaminergic (DA) neurons in the nigrostriatal pathway, which leads to progressive loss of motor and neurological function,” Larsen said in a statement.¹ "This is the first use of the autologous approach in a formal clinical trial, and it is an honor to be part of this important study."

In ASPIRO, trial inclusion states that only those who’ve had PD for at least 4 years and had an unequivocal motor response to levodopa will be included. The trial excludes those with prior brain surgery, a history of intracranial therapy for PD, uncontrolled diabetes or any other acute or chronic medical condition that would significantly increase the risks of neurosurgerical procedure. Additionally, those with a history of epilepsy, stroke, multiple sclerosis, poorly controlled or progressive neurological disease, or poorly controlled cardiovascular disease, are also excluded.

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Aspen’s personalized 3-step manufacturing approach starts from a small sample of the patient’s own skin cells, followed by reprogramming to induced pluripotent stem cells and then differentiation to dopamine neuronal precursor cells (DANPs). The DANPCs are then provided to the patient via surgery to replace their cells that were lost or damaged because of their disease. The quality of each person’s cells is assessed at each manufacturing stage using Aspen’s proprietary artificial intelligence-based genomics test.

"The initiation of this clinical trial is a major milestone in Aspen's mission to develop and deliver personalized, regenerative neurologic therapies for people with unmet medical needs, starting with Parkinson disease,” Damien McDevitt, PhD, Neuroscience president and chief executive officer at Aspen, said in a statement.¹ "To date, there is no disease-modifying therapy that can stop, replace or prevent the loss of dopamine neurons or slow the progression of Parkinson."

Stem cell transplantation, which has attracted widespread attention from researchers, is a relatively new treatment that has demonstrated potential for treating PD. Some of the most widely used stem cell sources for dopaminergic neuronal replacement include human embryonic stem cells (ESCs), human neuronal stem/progenitor cells (NSCs), human mesenchymal stem cells (MSCs), human fetal ventral midbrain cells, and human-induced pluripotent stem cells (iPSCs), like ANPD001.

Some of the advantages to iPSCs are their histocompatibility, ability to survive transplantation and rescue functional deficits, easily accessible source tissue, and minimal inmmunorejection and ethical issues. Genetic and epigenetic alterations, low reprogramming efficiency, and tumorigenic hazards, have been categorized as potential disadvantages to this approach.²

REFERENCES
1. Aspen Neuroscience announces first patient dosed in first-in-human phase 1/2a clinical trial of autologous neuronal cell replacement therapy for Parkinson’s disease. News release. Aspen Neuroscience. April 17, 2024. Accessed May 2, 2024. https://www.prnewswire.com/news-releases/aspen-neuroscience-announces-first-patient-dosed-in-first-in-human-phase-12a-clinical-trial-of-autologous-neuronal-cell-replacement-therapy-for-parkinsons-disease-302119216.html
2. Zeng X, Qin H. Stem cell transplantation for Parkinson’s disease: current challenges and perpsectives. Aging Dis. 2022;13(6):1652-1663. doi:10.14336/AD.2022.0312