Isomyosin expression patterns in embryonic chicken atria during the first two weeks of development were analyzed immunohistochemically. In the 3-days embryonic chicken heart (HH19-20), strong coexpression of both isomyosins can be found as band-like zones at the lateral sides of the sinoatrial junction. The zones converge on the bottom of the atrium and continue as a band around the atrioventricular canal. In the 5-days heart (HH27-28) the coexpression area encompasses the entire sinoatrial junction and extends into parts of the sinus venosus and into the dorsocaudal atrial wall. In the 7-days heart (HH 32-33) the relative extension of coexpression areas reaches its maximum. Coexpression is also found in a ring-like band in the ventral (bottom) wall of the atria peripheral to the ring-like band in the atrioventricular junction. The latter band has now become continuous with the coexpression area in the bottom of the interatrial septum. Caudally coexpression extends behind the atrioventricular cushions towards the interventricular septum and cranially coexpression of the atrioventricular junction has become continuous with that of the ring around the outflow tract (cf Sanders et al. 1986). In the second week of incubation a decrease of coexpression is observed. The isomyosin expression pattern described in this study has put forward additional arguments that the conductive tissue originates from areas that continue to express both isomyosins relatively late in development.

Background: The European Commission highlights in its Pharmaceutical Strategy the role of academic researchers in drug repurposing, especially in the development of orphan medicinal products (OMPs). This study summarizes the contribution of academia over the last 5 years to registered repurposed OMPs and describes barriers to success, based upon three real world cases.Methods: OMPs granted marketing authorization between January 2016 and December 2020 were reviewed for repurposing and whether the idea originated from academia or industry. Three cases of drug repurposing were selected from different therapeutic areas and stages of development to identify obstacles to success.Results: Thirteen of the 68 OMPs were the result of drug repurposing. In three OMPs, there were two developments such as both a new indication and a modified application. In total, twelve developments originated from academia and four from industry. The three cases showed as barriers to success: lack of outlook for sufficient return of investments (abatacept), lack of regulatory alignment and timing of interaction between healthcare professionals and regulators (etidronate), failure to register an old drug for a fair price, resulting in commercialization as a high priced orphan drug (mexiletine).Conclusion: While the majority of repurposed OMPs originates in academia, a gap exists between healthcare professionals, regulators and industry. Future strategies should aim to overcome these hurdles leading to more patient benefit through sustainable access of repurposed drugs. Potential solutions include improved regulatory and reimbursement knowledge by academia and the right for regulators to integrate new effectiveness data into product labels.

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