Lecture – Autologous iPSC-Based Cell Therapy for Parkinson’s Disease
Available with English captions.
Presented by Penny Hallett, PhD, McLean Hospital – McLean Forum lecture
Parkinson’s disease (PD), is characterized by tremor, bradykinesia (slowness of movement), rigidity, and postural instability. At the time of diagnosis, about 60% of the midbrain dopamine (mDA) neurons have already degenerated, resulting in a depletion of roughly 70% of striatal dopamine levels and synapses.
Watch now as McLean neuroscientist Penny Hallett, PhD, covers:
- Common Parkinson’s disease symptoms and treatments
- The rationale for using cell therapy to treat PD
- Research into the development of novel therapies for PD, including dopamine neuron replacement of synapses and restoration of circuitry
- New technologies, including the use of autologous iPSCs as a source of midbrain dopamine neurons
- Clinical trials planned by her team at McLean’s Neuroregeneration Institute
In her presentation, Hallett reports that using levodopa has long been the primary approach to these problems. This symptomatic treatment can restore dopamine levels and motor function. However, the treatment can lead to side effects like levodopa-induced dyskinesias (involuntary muscle movements).
To address this issue, researchers are seeking to achieve a physiological dopamine release in the brain. The only way to do this, Hallet asserts, is to “actually implant midbrain dopaminergic neurons into the brain.”
Hallett describes her past and current research into this approach.
She explains how cell replacement therapy with mDA neurons provides cellular and synaptic repair in the parkinsonian brain and addresses both the motor symptoms of PD as well as levodopa-induced dyskinesias. She details how investigations into fetal cell transplantation show that transplanted mDA neurons remain healthy and can provide remarkable therapeutic benefits for decades in PD patients.
In her talk, Hallett asserts that fetal cell transplantations are not scalable for a larger patient population and require immunosuppression. However, induced pluripotent stem cells (iPSCs) are a promising alternative cell source. iPSCs generated from PD patients can be differentiated into midbrain dopaminergic cells, frozen, and used for autologous transplantation—where the same person acts as the donor and recipient.
Hallett says that autologous iPSC-based cell therapy “opens the door for using the stem-cell-based approaches for other disease indications.” Moreover, she believes that “any neurological psychiatric disorder where we know there’s dysfunction in these brain circuitries could be used for neuronal transplantation approaches.”