Objective: To describe a new clinical trial testing the safety and efficacy of implanting autologous Dopamine Neuron Progenitor Cells (DANPCs) into the brain of patients with Parkinson’s Disease (PD) as regenerative therapy for dopamine deficiency caused by PD.
Background: PD affects the putamen through multiple mechanisms. Dopamine depletion occurs as PD causes a gradual loss of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced dopamine levels in the putamen. This dopamine depletion then contributes to motor dysfunction.
Additionally, the putamen can undergo atrophy, which is associated with both motor symptoms and cognitive impairment. PD can be managed with medications for a limited period, but PD has no cure. The standard treatments for PD have remained unchanged for several decades and do not slow the disease progression. Cell Replacement Therapy (CRT) presents an alternative approach that has the potential to restore striatal dopaminergic input and ameliorate debilitating motor symptoms in PD.
Methods: The ASPIRO clinical trial (Currently in Phase 1 and 2a) purports to be the first multi-center trial for an autologous neuron replacement therapy for Parkinson’s disease. The clinical trial tests an experimental biologic product derived from autologous skin cells converted to induced pluripotent stem cells. The stem cells are differentiated into Dopamine Neuron Progenitor Cells (DANPCs). Dose escalation will be achieved by bilateral injection of these DANPCs into the putamen. After drilling a burr hole in the skull, the neurosurgeon inserts a small catheter with the help of a smart frame through the parenchymal tissue to the putamen.
Data sources & results: The ASPIRO Trial is currently enrolling patients by invitation, but no results are yet available. The first trial patient has been successfully dosed with his autologous DANPCs.
Discussion: Case studies involving male patients with fetal nigral transplants in the striatum have demonstrated that the transplanted dopamine neurons can survive and reestablish connections in the striatum for a minimum of 10 years, even as the disease continues to progress and destroy the patients’ native dopamine neurons. Intraparenchymal injections are more surgically invasive than other administration routes. Still, they have some advantages: the dose of the vector can be lower when using intraparenchymal injections, and preexisting neutralizing antibodies have little effect on the transduction efficacy of biologics injected directly into the putamen. A prominent factor contributing to acute cell death during injection is the influence of mechanical forces on cells; specifically, the extensional force arising from differing velocities distorts cell length.

Keywords:Parkinson’s disease; Putamen; Caudate nucleus; Induced pluripotent stem cells; Sporadic Parkinson’s; Substantia nigra pars compacta; MRI-guided neurosurgery; Cell replacement therapy; Neurosurgical delivery