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One pathological hallmark of T2D is the toxic accumulation of human islet amyloid polypeptide (hIAPP) aggregates. Monomeric hIAPP is a hormone normally co\u2010secreted with insulin. However, increased levels of hIAPP in prediabetic and diabetic patients can lead to the formation of hIAPP protofibrils, which are toxic to <jats:italic>\u03b2<\/jats:italic> cells. Current therapies fail to address hIAPP aggregation and current screening modalities do not detect it. Using a stabilizing capping protein, monoclonal antibodies (mAbs) can be developed against a previously nonisolatable form of hIAPP protofibrils, which are protofibril specific and do not engage monomeric hIAPP. Shown here are two candidate mAbs that can detect hIAPP protofibrils in serum and hIAPP deposits in pancreatic islets in a mouse model of rapidly progressing T2D. Treatment of diabetic mice with the mAbs delays disease progression and dramatically increases overall survival. These results demonstrate the potential for using novel hIAPP protofibril\u2010specific mAbs as a diagnostic screening tool for early detection of T2D, as well as therapeutically to preserve <jats:italic>\u03b2<\/jats:italic> cell function and target one of the underlying pathological mechanisms of T2D.<\/jats:p>","DOI":"10.1002\/advs.202202342","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T21:59:45Z","timestamp":1666130385000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Human Islet Amyloid Polypeptide (hIAPP) Protofibril\u2010Specific Antibodies for Detection and Treatment of Type 2 Diabetes"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-4274","authenticated-orcid":false,"given":"Angelina S.","family":"Bortoletto","sequence":"first","affiliation":[{"name":"Center for Cell and Gene Therapy Stem Cells and Regenerative Medicine Center Department of Neuroscience Department of Molecular and Cellular Biology Translational Biology and Molecular Medicine Program Medical Scientist Training Program Baylor College of Medicine  One Baylor Plaza Houston TX 77030 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3815-7532","authenticated-orcid":false,"given":"W. 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