Pharmacological dopamine replacement therapies provide the most well-established treatments for Parkinson's disease (PD). However, these long-term treatments can lead to motor complications and off-target effects. ProSavin(®), a lentiviral vector (LV)-based gene therapy approach aimed at restoring local and continuous dopamine production, through delivery of three enzymes in the dopamine biosynthesis pathway, was demonstrated to be safe and well-tolerated in a phase I/II clinical study of patients with advanced PD. Although improvements in motor behaviour were observed, the data indicated that higher levels of dopamine replacement might be required to maximize benefit. We attempted to increase production of dopamine, and its precursor L-Dopa in LV-transduced cells, by optimizing the gene order in the ProSavin expression cassette, and by creating fusions of two or three of the transgenes, using linker sequences. In vitro analysis showed that several gene arrangements provided significantly increased dopamine and/or L-Dopa production compared with ProSavin, and that LV titers and transgene expression were not affected by introducing gene fusions. One vector, equine infectious anemia virus (EIAV)-TCiA, was selected for further characterization and showed significant improvements in dopamine and L-Dopa production compared with ProSavin, in human neuronal cells. Further characterization of EIAV-TCiA demonstrated expression of all three dopamine enzymes in vivo and faithful delivery and integration of the expected gene expression cassette within the genome of target cells, as assessed by Northern and Southern blotting. In conclusion, we have developed a novel LV vector with an increased capacity for L-Dopa and dopamine production compared with the current ProSavin vector. Clinical evaluation of this vector will be performed to assess the benefits in patients with PD.

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Using data collected from 277 buyers employed at large purchasing organizations (LPOs) in the U.S. and U.K., this study investigates factors that might influence their willingness to procure goods and services from ethnic minority businesses (EMBs). The social capital literature is used to develop hypotheses concerning the cognitive, structural, and relational dimensions that may play roles in decisions to buy from minority firms. Subsequently, modern discrimination theory is employed to provide inductive insights into how buyers' attitudes toward supplier diversity mediate the effects of social capital on their procurement activities with EMBs. The results of multiple regression analysis suggest that in both the U.S. and U.K., positive social capital as perceived by the buyers has a direct, significant relationship with their expenditures with EMBs. The results also reveal that in both countries, buyers' attitudes toward supplier diversity mediate the relationship. Interestingly, although the U.S. originated the concept of supplier diversity, our research uncovers that U.K. LPO buyers have greater expenditures with their EMBs. Based on these findings, this research illustrates how strategic corporate social responsibility initiatives set forth by LPOs may be impacted by their buyers' social relationships with EMBs and their attitudes toward supplier diversity.

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Supplier diversity programs were created in the United States nearly 50 years ago to encourage private sector companies to provide business opportunities to underutilized minority business enterprises. In order to assess the experiences that minority business enterprise CEOs have with large purchasing organizations and their perceptions of justice and commitment of large purchasing organizations to the buyer–supplier relationship (BSR), this study utilizes survey data collected from 206 minority business enterprise CEOs who supply large purchasing organizations that espouse a strong commitment to supplier diversity. The theoretical framework of organizational justice is utilized to establish testable hypotheses. The results from hierarchical linear regression show minority business enterprise CEOs’ perception of large purchasing organizations’ commitment to the BSR is positively related to the distributive and informational dimensions of organizational justice. Surprisingly, the procedural dimension was found to have a significantly negative relationship. This research also found a significant, negative relationship between minority firm CEOs’ perception of distributive and informational justice and their perceptions of unethical behavior by large purchasing organizations.