Kev.....thanks, The conclusion on this Sigma-1 Research Analysis has some pertinent points....low overall level of research... lack of scientific collaboration....virtually no drugs developed and approved. So we may be the "Lone Ranger" in the Sigma-1 drug development for neurodegeneration, however we will have a lot of "Tontos" coming to the campfire when we are successful. In the meantime Anavex should and is educating the Pharma community about Sigma-1 homeostasis.
Highlighted important points.
"Conclusions
In this work, the global scientific outputs of Sigma-1 receptor research, its main research lines and its evolution are studied for the first time by means of bibliometric indicators of a basic nature and modern information visualization techniques. The resulting maps are a useful and attractive tool for the Sigma-1 receptor research community, as they reveal the main lines of exploration at a glance. The global view provided by our study shows that researchers have intended to explore the potential involvement of Sigma-1 receptors in some specific physiological processes and diseases. The hope that the modulation of the Sigma-1 receptor could be a therapeutic strategy is likely driving the Sigma-1 research community. Consistent with this, intensive activity has been carried out in the area of Medicinal Chemistry to obtain selective ligands that could be developed as drugs in the future. According to our analysis, the main diseases in which the Sigma-1 receptors have been explored include addiction, neuroprotection and neurodegenerative diseases, psychiatric disorders, and pain. Keyword co-occurrence analysis suggests that the research efforts made in some indications such as those in cocaine (addiction), learning and memory or depression/schizophrenia/ haloperidol (psychiatric conditions) have declined over time, while others such as those focusing on neuroprotection/Alzheimer's disease (neurodegenerative diseases) or pain are currently most popular. Early studies on psychiatric disorders, learning and memory or cocaine did not translate into marketed drugs, and hopes now seem to be placed on studies relating to neurodegenerative diseases and pain. Leaving aside the well-known low success in transforming basic research into new drugs with a clear therapeutic potential and difficulties related to drug discovery programs (Paul et al., 2010), the lack of selective Sigma-1 ligands approved for use in humans could be the result of insufficient research effort/interest by the scientific community, including biopharmaceutical companies. In fact, only 247 authors have five or more publications and the growth in the production of articles is not constant over time, with periods of stagnation of approximately 5 years. The authors appear grouped in relatively independent clusters, thus suggesting a low level of collaboration between those devoted to the Sigma-1 receptor. Furthermore, as evidenced by the number of recent articles, only one pharmaceutical company, developing selective Sigma-1 receptor drug ligands, is currently actively publishing in the field. Additionally, the very nature of the Sigma-1 receptor may also be influencing the low success in transforming basic research into new drugs with a clear therapeutic potential. It is common in papers to describe the Sigma-1 receptor as an “enigmatic protein whose molecular mechanism of action remains elusive.” The most cited article we found in this bibliometric analysis (Hayashi and Su, 2007) proposed that the Sigma-1 receptor acts as a molecular chaperone and therefore is not a traditional receptor. Chaperones ensure that all proteins obtain their correct folding and functionalities in the right localization at the right time. They recognize and bind their protein clients in conformational ensembles that are locally highly dynamic and interconvert, while in other cases clients bind in unique conformations (Hiller, 2019). Thus, to transform basic research into new drugs with a clear therapeutic potential, the intrinsic difficulty when trying to understand the mysteries of this unique ligand-regulated molecular chaperone should be considered in drug discovery programs.
In summary, a greater interest and involvement of the scientific community for this enigmatic chaperone, accompanied by a parallel increase in the scientific production would help, hopefully in coming years, to the discovery of new functions and deepening in those already known. Additional boost needed to improve research performance are likely to come from new conceptual frameworks and breakthrough discoveries derived from recent and future advances in the “chaperone field,” and from collaborative, synergistic initiatives by combining resources and knowhow from different laboratories to overcome the limitations of the individual approaches. This study may provide a valuable basis for identifying important topics for future research, and create opportunities for collaboration between research groups with complementary scientific interest in the field of Sigma-1 receptor."
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