Real-time magnetic resonance imaging during convective gene therapy in the brain

Real-time magnetic resonance imaging (MRI) during gene therapy in the nervous system has a fundamental impact on optimizing the effectiveness, safety and efficiency of gene therapy delivery to the nervous system. the nervous system.

Researchers from the Ohio State University Gene Therapy Institute and the Ohio State University Wexner Medical Center and College of Medicine explain more in the journal JAMA Surgery.

Direct intraparenchymal delivery of gene therapy for neurodegenerative, metabolic, and enzyme deficiency diseases has been used in a number of “first-in-human” clinical trials around the world, including several led by Krzysztof S. Bankiewicz, MD, PhD

Ohio State is pioneering this specific type of gene therapy delivered directly into the parenchyma, a type of tissue made up of cells that serve an essential function in the nervous system.

“Real-time magnetic resonance imaging of gene therapy delivery to the nervous system will be more widely applied over the next three to five years as more sites become equipped with the necessary infrastructure and expertise continues to increase,” said co-author Bankiewicz, who is scientific director of the Gene Therapy Institute and professor of surgery in the Department of Neurosurgery at Ohio State.

Adoption of this innovation will continue to grow rapidly with the increasing use of intraparenchymal gene therapy and may be applied to future trials and associated clinical care. Specifically, it can improve safety, understanding of distribution parameters and information about effectiveness, said Bankiewicz, the Gilbert and Kathryn Mitchell Endowed Chair at Ohio State Wexner Medical Center.

The use of image-guided direct intraparenchymal gene therapy in the brain has been defined in several neurological disorders, including neurodegenerative disorders (Alzheimer’s, Huntington’s, and Parkinson’s diseases) and neurotransmitter disorders.

“Ultimately, this should improve the biological and clinical understanding of treatments, which will lead to optimal clinical care for patients undergoing direct intraparenchymal gene therapy of the nervous system. Additionally, the imaging results will illuminate information criticisms which could lead to future improvements in the administration parameters.” said first corresponding author Asad S. Akhter, MD, a neurosurgery resident at Ohio State.

Bankiewicz led studies with children who underwent gene therapy for the treatment of the neurotransmitter disorder aromatic amino acid decarboxylase deficiency (AADC). Because they lack the AADC enzyme, patients with AADC deficiency cannot produce the neurotransmitters dopamine and serotonin.

Pre-infusion clinical findings included developmental delay, lack of verbalization, hypotonia, disabling oculogyric seizures, lack of nuchal control, autonomic dysfunction, and inability to sit, stand or to walk independently. After infusion, patients experienced complete resolution of oculogyric crises, improved autonomic control, and regained the ability to sit independently, walk, and talk.

The use of real-time MR imaging during convective gene therapy has several advantages, including the ability to confirm precise cannula placement and optimize perfusion of the target structure.

“This type of innovative gene therapy allows for maximum perfusion of the target site using perfusion-as-you-go techniques,” said co-author Russell Lonser, MD, director of the State Gene Therapy Institute. of Ohio and professor and chair of the Gene Therapy Institute at Ohio State. Department of Neurosurgery.