{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:20:47Z","timestamp":1779916847079,"version":"3.53.1"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Developing and implementing clinical trials for rare diseases is complicated by the incomplete understanding of the varied genotype and subsequent phenotypic differences of a condition, particularly when low numbers of subjects are enrolled in a study. Moreover, a small-scale clinical study may indicate a positive outcome but have too small of a sampling population to adequately evaluate unwanted outcomes. Prader\u2013Willi syndrome (PWS) is one such genetic disorder with varied subtypes and heterogeneity, where little progress has been made in treatment discoveries. Recently, the FDA approved diazoxide choline for treating key features of hyperphagia and obesity associated with PWS based on clinical trial experience. Diazoxide choline activates the ATP-sensitive potassium channel (KATP) of pancreatic beta cells, inhibiting the release of insulin. One of the subunits of KATP is the protein Kir6.2, the gene product of KCNJ11. Methods: Web-based programs and datasets were used to study the gene and protein functional enrichments of Kir6.2 and KCNJ11, including shared gene and\/or protein\u2013protein interactions, and biological processes and functions. Results: Four essential domains of related functions were identified: (1) apoptosis, protein degradation, and inflammation; (2) the coupling of G proteins needed for KATP channel activation; (3) glucose metabolism and control; and (4) the maintenance of intracellular ionic homeostasis. Conclusions: Cellular metabolism in the pancreas is linked to membrane excitability by KATP, which regulates insulin production, energy production and storage, appetite regulation, and fatty acid synthesis. As such, diazoxide choline may influence several biological systems beyond pancreatic and metabolic functions.<\/jats:p>","DOI":"10.3390\/genes16121436","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:03:02Z","timestamp":1764594182000},"page":"1436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Barriers, Limitations, and Experiences with Clinical Trials\u2014Treatment in Rare Diseases with Prader\u2013Willi Syndrome as an Example"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2911-0524","authenticated-orcid":false,"given":"Merlin G.","family":"Butler","sequence":"first","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Silvey","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4033-6540","authenticated-orcid":false,"given":"Harold J. P.","family":"van Bosse","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","unstructured":"US Food and Drug Administration (2005, May 15). Rare Diseases at FDA, Available online: https:\/\/www.fda.gov\/patients\/rare-diseases-fda."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, C.M., Whiting, A.H., Rath, A., Anido, R., Ardig\u00f2, D., Baynam, G., Dawkins, H., Hamosh, A., Le Cam, Y., and Malherbe, H. (2024). Operational description of rare diseases: A reference to improve the recognition and visibility of rare diseases. Orphanet J. Rare Dis., 19.","DOI":"10.1186\/s13023-024-03322-7"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Butler, M., Lee, P., and Whitman, B. (2022). 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