Drug repurposing for rare: progress and opportunities for the rare disease community

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases’ ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development

D/H variation in terrestrial lipids from Santa Barbara Basin over the past 1400 years: A preliminary assessment of paleoclimatic relevance

We analyzed D/H ratios of common terrestrial leaf wax lipids in a 1400 year sediment core from the Santa Barbara Basin (SBB) to test whether they accurately record terrestrial climate in Southern California. The D/H ratios of long chain n-alkanes vary substantially with depth, but are poorly correlated with other terrestrial climate proxies. Interference from fossil hydrocarbons may be at least partly responsible. Long chain n-alkanoic acids exhibit nearly constant downcore D/H ratio values. This constancy in the face of known climatic shifts presumably reflects a substantial residence time for leaf wax compounds in terrestrial soil and/or on the basin flanks. Alternatively, the isotopic composition of meteoric waters in Southern California may not covary with climate, particularly aridity. However, the δD values of n_(-C22) and n_(-C24) fatty acids, commonly attributed to terrestrial aquatic sources, are partially correlated with Southern California winter Palmer Drought Severity Index, a tree ring-based climatic proxy (R^2 0.25; p < 0.01) on multi-centennial scales with an inferred ca. 215 year time lag. The improved correlation of these biomarkers can be explained by the fact that they are not stored in terrestrial soil nor are subject to interference from fossil hydrocarbons. Our study indicates that the SBB is unlikely to preserve high resolution leaf wax D/H records that can serve as quantitative paleoclimate proxies, though some qualitative information may be retained. More generally, the sources of lipids in marginal marine basins need to be carefully evaluated prior to attempting paleoclimate reconstruction based on the leaf wax D/H proxy