Researchers' Work from University of Medicine and Dentistry of New Jersey (UMDNJ) Focuses on Gene Therapy (Comparison of Endovascular and Intraventricular Gene Therapy With Adeno-Associated Virus-alpha-L-Iduronidase for Hurler Disease)
By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Investigators publish new report on Biotechnology. According to news originating from Newark, New Jersey, by NewsRx correspondents, research stated, "Hurler disease (mucopolysaccharidosis type I [MPS-I]) is an inherited metabolic disorder characterized by deficiency of the lysosomal enzyme alpha-L-iduronidase (IDUA). Currently, the only therapies for MPS-I, enzyme replacement and hematopoietic stem cell transplantation, are generally ineffective for central nervous system manifestations."
Our news journalists obtained a quote from the research from the University of Medicine and Dentistry of New Jersey (UMDNJ), "To test whether brain-targeted gene therapy with recombinant adeno-associated virus (rAAV5)-IDUA vectors in an MPS-I transgenic mouse model would reverse the pathological hallmarks. Gene therapy approaches were compared using intraventricular or endovascular delivery with a marker (rAAV5-green fluorescent protein) or therapeutic (rAAV5-IDUA) vector. To improve the efficiency of brain delivery, we tested different applications of hyperosmolar mannitol to disrupt the blood-brain barrier or ependymal-brain interface. Intraventricular delivery of 1 x 10(11) viral particles of rAAV5-IDUA with systemic 5 g/kg mannitol co-administration resulted in IDUA expression throughout the brain, with global enzyme activity >200% of the baseline level in age-matched, wildtype mice. Endovascular delivery of 1 x 10(12) viral particles of rAAV5-IDUA to the carotid artery with 29.1% mannitol blood-brain barrier disruption resulted in mainly ipsilateral brain IDUA expression and ipsilateral brain enzyme activity 42% of that in wild-type mice. Quantitative assays for glycosaminoglycans showed a significant decrease in both hemispheres after intraventricular delivery and in the ipsilateral hemisphere after endovascular delivery compared with untreated MPS-I mice. Immunohistochemistry for ganglioside GM3, another disease marker, showed reversal of neuronal inclusions in areas with IDUA co-expression in both delivery methods. Physiologically relevant biochemical correction is possible with neurosurgical or endovascular gene therapy approaches for MPS-I."
According to the news editors, the research concluded: "Intraventricular or endovascular delivery of rAAV5-IDUA was effective in reversing brain pathology, but in the latter method, effects were limited to the ipsilateral hemisphere."
For more information on this research see: Comparison of Endovascular and Intraventricular Gene Therapy With Adeno-Associated Virus-alpha-L-Iduronidase for Hurler Disease. Neurosurgery, 2014;74(1):99-111. Neurosurgery can be contacted at: Lippincott Williams & Wilkins, 530 Walnut St, Philadelphia, PA 19106-3621, USA. (Lippincott Williams and Wilkins - www.lww.com; Neurosurgery - journals.lww.com/neurosurgery/pages/default.aspx)
The news correspondents report that additional information may be obtained from C.G. Janson, Medical & Dental University New Jersey, Sch Med, Cell & Gene Therapy Center, Newark, NJ 07103, United States. Additional authors for this research include L.G. Romanova, P. Leone, Z.H. Nan, L. Belur, R.S. McIvor and W.C. Low (see also Biotechnology).
Keywords for this news article include: Biotechnology, Newark, Virology, Angiology, New Jersey, Gene Therapy, United States, Bioengineering, Hurler Disease, Blood Brain Barrier, Blood-Brain Barrier, Enzymes and Coenzymes, Adeno-Associated Virus, North and Central America, Central Nervous System Diseases
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