Success of gene therapy for neurological disorders depends on precise and reproducible intracranial delivery of viral vectors that encode therapeutic genes. However, optimal viral vector delivery into the brain is challenging and brain distribution of viral vectors is uncertain. Parameters required for optimal delivery such as volume, rate of infusion, and cannula placement had to be defined experimentally to predict desired coverage of each anatomical target to avoid introducing the vector to regions outside the target, including cerebrospinal fluid (CSF).
A team of scientists, led by Dr. Krystof Bankiewicz, University of California-San Francisco, presented this significant advance, which allows, for the first time, to adjust parameters of vector infusion while delivering gene therapy, giving surgeon full control over gene transfer technology.
To demonstrate applicability of this technology, adeno-associated viral (AAV) vectors were co-administered together with gadolinium (MRI-contrast agent) nano-liposomes into several brain regions in monkeys under MRI control.
With this technology, AAV delivery can be monitored in real time during AAV administration, thus, precise gene expression over small and large targets can be assured increasing safety and efficacy of AAV administration to the brain and spinal cord.
The American Society of Gene Therapy is a professional non-profit medical and scientific organization dedicated to the understanding, development and application of gene and related cell and nucleic acid therapies and the promotion of professional and public education in the field. For more information, visit
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Four weeks after the treatment, rats administered HSV-GDNF exhibited significant recovery of intracavernous pressure (ICP) and systemic arterial pressure (AP) compared with rats treated with the control virus or untreated mice with ED. Rats treated with HSV-neurturin also exhibited significant recovery of ICP and AP compared with the control or untreated mice at four weeks after treatment. Fluorescent protein studies also showed that the delivered genes had been effectively incorporated into the target nerve cells.
According to Dr. Glorioso, HSV delivery of GDNF or neurturin presents a potentially important new approach for the treatment of ED. "Because the herpes virus persists in the nerve cell for as long as it is alive and nerve cells typically do not reproduce, this represents the first-ever demonstration of a long-term treatment for ED that does not rely on the chronic administration of drugs that can have potentially harmful side effects," he explained.
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