Objective/Rationale:
Glial cell line-derived neurotrophic factor (GDNF) is a protein that can aid in survival of the dopamine cells that die in Parkinson’s disease (PD). Treatment with GDNF in PD has been difficult because the protein has to be applied to the appropriate brain regions. Encapsulated cell therapy implants containing a human cell line engineered to secrete GDNF for an extended time in the human brain aim to solve this problem.
Project Description:
This project builds on a previous MJFF-funded study that indicated that GDNF levels from encapsulated cell therapy need to be increased to meet the therapeutic goals. Therefore, using new technology called transposon-based gene expression, we generated a cell line capable of producing therapeutic levels of GDNF. This new cell line will be applied in encapsulated cell therapy implants and evaluated in a pre-clinical model to ensure efficacy and safety before proceeding to human clinical trials.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Unlike current symptomatic therapies, the GDNF-secreting implants aim not only to improve the symptoms but also to promote the regeneration and protection of dopaminergic brain cells to slow progressive cell death and functional disability.
Anticipated Outcome:
We anticipate that three to four encapsulated cell therapy devices containing the transposon-engineered cell line will be able to deliver safe and therapeutically relevant levels of GDNF to each putamen in humans. The pre-clinical model enables testing of the clinical implants in a comparable manner and brain region as anticipated in the clinic and will help ensure placement and dosage.
Progress Report
GDNF-secreting cellular brain implants have been successfully generated and tested for sustained secretion in the relevant brain region (striatum) in pre-clinical models. Excellent long-term secretion and therapeutic tissue levels of GDNF have been demonstrated, and a clinically relevant and stable cell line has been banked under good manufacturing practice (GMP). Clinically relevant implants have also been built and are being successfully tested in a pre-clinical safety study to support an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA).
Presentations
The Principal Investigator was invited to present the project at a satellite symposium entitled “From History of Neuroscience to New Horizons” associated with the International and Parkinson Movement Disorder Society annual congress in Stockholm, Sweden on June 7, 2014.
June 2014
PARTNERING PROGRAM
This grant was selected by The Michael J. Fox Foundation staff to be highlighted via the Foundation’s Partnering Program.