# Parkinsons disease scalable iPSC autologous cell therapy

> **NIH NIH U01** · MCLEAN HOSPITAL · 2021 · $1,640,000

## Abstract

Abstract:
This is a revised application, modified to fully respond to reviewers’ comments and FDA interactions since the
application (FDA pre-IND meeting held on Sept. 25, 2018). The proposed work will complete IND-enabling
studies to progress cell replacement paradigms into the clinic using induced pluripotent stem cell (iPSC)-
derived dopamine (DA) neurons, and a first-in-man clinical trial for autologous transplantation in Parkinson’s
disease (PD). Cell replacement therapy with midbrain dopamine (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. Our previous fetal cell transplantation work shows that in PD patients transplanted mDA neurons
remain healthy and can provide remarkable therapeutic benefit for decades. While fetal cell transplantations
are not scalable for a larger patient population and require immunosuppression, 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.
The NINDS CREATE Bio Development Track U01 proposal over 5 years consists of milestones within four
Specific Aims, that includes a Phase I clinical trial in human patients with PD. In Specific Aim 1 we will transfer
the remaining mDA neuron product quality control assays for qualification in the cGMP facility, perform FDA-
guided quality control of excipients for the clinical product, and produce mDA neurons to be used in IND-
enabling studies. In Specific Aim 2, definitive IND-enabling studies will be performed to test the safety
(tumorigenicity and biodistribution) and efficacy of human iPSC-derived frozen-thawed mDA neurons in
rodents, as well as testing of the planned clinical delivery device in non-human primates. Specific Aim 3 will
include IND package preparation and filing for an Investigator-initiated Phase I clinical trial, recruitment of
patients with PD and generation of autologous cGMP iPSCs and mDA neurons as well as release criteria
testing of the cryopreserved clinical product. Finally, Specific Aim 4 is a first-in-human clinical Phase I
interventional, open-label clinical trial in 6 patients with sporadic PD, to test the safety and efficacy of
autologous transplantation of frozen-thawed mDA neurons.
This highly innovative autologous CMC iPS cell technology U01 proposal for cell replacement clinical trials in
PD patients provides a necessary step and exploration for the development of successful cell therapy for PD
and several neurological disorders.

## Key facts

- **NIH application ID:** 10073557
- **Project number:** 5U01NS109463-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** PENELOPE Jane HALLETT
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,640,000
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073557

## Citation

> US National Institutes of Health, RePORTER application 10073557, Parkinsons disease scalable iPSC autologous cell therapy (5U01NS109463-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073557. Licensed CC0.

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