# Non-Invasive Tracking of Genome-Corrected iPS cells in ALS

> **NIH NIH UH2** · JOHNS HOPKINS UNIVERSITY · 2020 · $238,962

## Abstract

The use of gene-edited stem cells and in particular patient-derived iPSCs for cell replacement therapy is an
appealing approach for genetic correction of a disease-associated gene mutation. If such therapies are
pursued in future patients, it would be highly desirable to have non-invasive cell tracking techniques available
that can report longitudinally on the distribution and survival of transplanted cells, in order to better understand
their fate in vivo and to optimize personalized therapies. We have chosen amyotrophic lateral sclerosis (ALS),
a devastating disease with near 100% mortality as an example of a target disease, in which loss of motor
neurons is a key event leading to muscle paralysis. For familial forms of ALS, mutations in the gene superoxide
dismutase 1 (SOD1) are known to be a causative factor for disease development. In this proposal, we aim to
apply two novel experimental imaging modalities (MPI and PSMA-targeted 18F-DCFPyL PET) in conjunction
with a clinically emerging technique (1H MRI) to answer several basic questions associated with the efficacy
and safety of genome-edited cell therapy. These are complementary techniques, where MPI and PSMA-
targeted 18F-DCFPyL PET can report on the whole-body distribution of administered cells, whereas MRI can
report on real-time homing and immediate retention of cells. This three-pronged approach of imaging the same
cell (labeled with SPIO for MPI and MRI, and 18F-DCFPyL for PET) will be applied for tracking of patient-
derived native (39b-SOD1+/AV4) and genome-corrected (39b-SOD1+/+) iPSCs, with and without differentiation
into motor neurons, in a transgenic SOD1G37R mouse model of ALS. Intra-arterial injection, an emerging cell
delivery route, will be used to study the feasibility of real-time image-guided cell injections aimed at obtaining a
more global cerebral cell distribution, while intraparenchymal injection in the spinal cord will be applied as a
clinically effective delivery technique to deliver cells locally at the site of impaired motor neurons. If successful,
this example imaging application of genome-corrected cells in ALS may encourage the use of MPI, MRI,
and/or PMSA-based PET imaging to interrogate the fate of cells in other disease scenarios in vivo.

## Key facts

- **NIH application ID:** 10006002
- **Project number:** 5UH2EB028904-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jeff W. Bulte
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,962
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006002

## Citation

> US National Institutes of Health, RePORTER application 10006002, Non-Invasive Tracking of Genome-Corrected iPS cells in ALS (5UH2EB028904-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10006002. Licensed CC0.

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