28 research outputs found
CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder
A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals
Condom social marketing program to prevent HIV/AIDS in post-conflict Liberia
Background: Youths in sub-Saharan Africa (SSA) account for a large
burden of the global HIV/STI crises. As such, strategies directed at
promoting behavioral modifications would be critical to reducing the
prevalence of risky sexual behaviors among high risk adolescents in
post-conflict environments. Objectives: This study describes a condom
promotion strategy to prevent HIV/STIs among highly vulnerable urban
youth in a post-conflict, resource-constrained environment via the
provision of both male and female condoms to nontraditional venues like
music and photo shops, ice cream parlors, money exchange centers and
beauty salons. Methods: Community members in the designated catchment
areas volunteered their services and the use of their small businesses
to support this endeavor. Results: In this paper, we describe the
condom promotion strategy and its implications within the context of a
communitybased participatory social marketing program to prevent risky
sexual behaviors among highly vulnerable urban youth in a post-conflict
country. Conclusion: We postulate that this approach may likely
increase condom use among urban youth in Monrovia, the capital city of
Liberia