MR‐Guidance of Gene Therapy for Brain Diseases: Moving From Palliative Treatment to Cures DOI Creative Commons
Dalton Bermudez, Thomas Lilieholm, Walter F. Block

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

ABSTRACT Regulatory bodies in the U.S. and Europe recently approved a gene therapy for aromatic L‐amino acid decarboxylase (AADC) deficiency, rare neurologic disorder where genetic mutation prevents dopamine production brain. Affected children fail to develop normal motor cognitive functions. MRI‐guided intraparenchymal delivery of AADC localized gray matter regions—specifically substantia nigra ventral tegmental area—has enabled brain produce dopamine, resulting dramatic improvements physical outcomes. The need target only small region simplifies surgical approach. However, broader neurodegenerative conditions has progressed more slowly than expected, despite significant global investment. Clinical efficacy depends heavily on accurate therapeutics via direct infusion, cerebrospinal fluid (CSF) administration, or both. Inadequate image guidance during clinical trials makes it difficult distinguish between true drug inefficacy failure. We highlight how increasing use MRI pre‐surgical simulation real‐time monitoring is accelerating development neurological diseases. This manuscript explores MRI's role guiding delivery, particularly using Convection Enhanced Delivery (CED). contributes across treatment timeline—from planning infusion validating therapeutic coverage. describe supports controlled distribution treatments its potential enable distributions needed correcting widespread anomalies. also detail structural anatomical sequences (T1, T2, Time Flight, Diffusion Tensor Imaging (DTI)) can help model likely distributions. Finally, we provide an outlook advanced DTI‐based algorithms poroelastic theory could further improve modeling dynamics. Current MRI‐based technologies be integrated enhanced CED effectiveness, especially very young pediatric patients. Evidence Level 1. Technical Efficacy Stage 4.

Language: Английский

MR‐Guidance of Gene Therapy for Brain Diseases: Moving From Palliative Treatment to Cures DOI Creative Commons
Dalton Bermudez, Thomas Lilieholm, Walter F. Block

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

ABSTRACT Regulatory bodies in the U.S. and Europe recently approved a gene therapy for aromatic L‐amino acid decarboxylase (AADC) deficiency, rare neurologic disorder where genetic mutation prevents dopamine production brain. Affected children fail to develop normal motor cognitive functions. MRI‐guided intraparenchymal delivery of AADC localized gray matter regions—specifically substantia nigra ventral tegmental area—has enabled brain produce dopamine, resulting dramatic improvements physical outcomes. The need target only small region simplifies surgical approach. However, broader neurodegenerative conditions has progressed more slowly than expected, despite significant global investment. Clinical efficacy depends heavily on accurate therapeutics via direct infusion, cerebrospinal fluid (CSF) administration, or both. Inadequate image guidance during clinical trials makes it difficult distinguish between true drug inefficacy failure. We highlight how increasing use MRI pre‐surgical simulation real‐time monitoring is accelerating development neurological diseases. This manuscript explores MRI's role guiding delivery, particularly using Convection Enhanced Delivery (CED). contributes across treatment timeline—from planning infusion validating therapeutic coverage. describe supports controlled distribution treatments its potential enable distributions needed correcting widespread anomalies. also detail structural anatomical sequences (T1, T2, Time Flight, Diffusion Tensor Imaging (DTI)) can help model likely distributions. Finally, we provide an outlook advanced DTI‐based algorithms poroelastic theory could further improve modeling dynamics. Current MRI‐based technologies be integrated enhanced CED effectiveness, especially very young pediatric patients. Evidence Level 1. Technical Efficacy Stage 4.

Language: Английский

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