Stereotaxic-assisted gene therapy in Alzheimer's and Parkinson's diseases: therapeutic potentials and clinical frontiers

Samar O El Ganainy, Tony Cijsouw,Mennatallah A Ali,Susanne Schoch,Amira Sayed Hanafy

EXPERT REVIEW OF NEUROTHERAPEUTICS(2022)

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摘要
Introduction: Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders causing cognitive deficits and motor difficulties in the elderly. Conventional treatments are mainly symptomatic with little ability to halt disease progression. Gene therapies to correct or silence genetic mutations predisposing to AD or PD are currently being developed in preclinical studies and clinical trials, relying mostly on systemic delivery, which reduces their effectiveness. Imaging-guided stereotaxic procedures are used to locally deliver therapeutic cargos to well-defined brain sites, hence raising the question whether stereotaxic-assisted gene therapy has therapeutic potentials. Areas covered: The authors summarize the studies that investigated the use of gene therapy in PD and AD in animal and clinical studies over the past five years, with a special emphasis on the combinatorial potential with stereotaxic delivery. The advantages, limitations and futuristic challenges of this technique are discussed. Expert opinion: Robotic stereotaxis combined with intraoperative imaging has revolutionized brain surgeries. While gene therapies are bringing huge innovations to the medical field and new hope to AD and PD patients and medical professionals, the efficient and targeted delivery of such therapies is a bottleneck. We propose that careful application of stereotaxic delivery of gene therapies can improve PD and AD management.
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关键词
Neurodegeneration, siRNA, CRISPR, stereotaxis, nanocarriers
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