Natalizumab: targeting alpha4-integrins in multiple sclerosis

In 1992, it was shown that monoclonal antibodies blocking alpha(4)-integrins prevent the development of experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (MS). As alpha(4)beta(1)-integrin was demonstrated to mediate the attachment of immune-competent cells to inflamed brain endothelium in experimental autoimmune encephalomyelitis, the therapeutic effect was attributed to the inhibition of immune cell extravasation and inflammation in the central nervous system. This novel therapeutic approach was rapidly and successfully translated into the clinic. The humanized anti-alpha(4)-integrin antibody natalizumab demonstrated an unequivocal therapeutic effect in preventing relapses and slowing down the pace of neurological deterioration in patients with relapsing-remitting MS in phase II and phase III clinical trials. The occurrence of 3 cases of progressive multifocal leukoencephalopathy in patients treated with natalizumab led to the voluntary withdrawal of the drug from the market. After a thorough safety evaluation of all patients receiving this drug in past and ongoing studies for MS and Crohn's disease, natalizumab again obtained approval in the US and the European Community. A treatment targeting leukocyte trafficking in MS has now re-entered the clinic. Further thorough evaluation is necessary for a better understanding of the risk-benefit balance of this new treatment option for relapsing MS. In this review, we discuss the basic mechanism of action, key clinical results of clinical trials and the emerging indication of natalizumab in MS.

AGROFORESTRY ADDRESSING SOCIAL AND ENVIRONMENTAL ISSUES IN PARAGUAY

Paraguay is characterized in part by an economy reliant on a massive soy industry and as facing social and economic challenges resulting from highly inequitable distribution of wealth and land ownership, particularly for smallholder farmers in the rural areas of the country. Yerba mate (Ilex paraguariensis), a native tree of which the leaves are used in tea, has become an increasingly common crop grown among common among smallholder farmers (owners of 10 hectares or less) as a viable alternative to soy production on a small scale. In the rural agricultural community of Libertad del Sur, located in the heart of the severely deforested Bosque Atlántico del Alto-Paraná, a series of development initiatives including tree nurseries and agroforestry projects with yerba mate were implemented with involvement of several governmental and nongovernmental organizations. Research was conducted to identify effectiveness of an agroforestry strategy to promote reforestation activities and sustainable agriculture to achieve economic and subsistence goals of the rural population. Despite a severe drought impacting initial research goals, important lessons are considered regarding promotion of development work within the community as well as community perceptions towards development agencies. Pursuit of compromise between community member and agency goals using sustainable agricultural practices is identified as an effective means to promote mutually beneficial development strategies.