RESUMO
AbstractPsychiatric treatment options, such as electroconvulsive therapy (ECT), can be lifesaving for individuals suffering from severe mental illness. For individuals who are unable to make or communicate their own medical decisions, this decision may fall on a legal guardian, who will make decisions on the patient's behalf. Here we discuss the considerations of end-of-life planning in a patient with severe mental illness under guardianship when treatment modalities, in this case ECT, are no longer effective.
Assuntos
Eletroconvulsoterapia , Cuidados Paliativos , Assistência Terminal , Veteranos , Humanos , Feminino , Idoso , Tutores Legais , Tomada de Decisões , Depressão/terapia , Planejamento Antecipado de CuidadosRESUMO
Activity of the heme synthesis enzyme ferrochelatase (FECH) is implicated in multiple diseases. In particular, it is a mediator of neovascularization in the eye and thus an appealing therapeutic target for preventing blindness. However, no drug-like direct FECH inhibitors are known. Here, we set out to identify small-molecule inhibitors of FECH as potential therapeutic leads using a high-throughput screening approach to identify potent inhibitors of FECH activity. A structure-activity relationship study of a class of triazolopyrimidinone hits yielded drug-like FECH inhibitors. These compounds inhibit FECH in cells, bind the active site in cocrystal structures, and are antiangiogenic in multiple in vitro assays. One of these promising compounds was antiangiogenic in vivo in a mouse model of choroidal neovascularization. This foundational work may be the basis for new therapeutic agents to combat not only ocular neovascularization but also other diseases characterized by FECH activity.