Peptide-mediated apheresis for inflammatory bowel diseases

描述（由申请方提供）：炎症性肠病（IBD）主要包括溃疡性结肠炎（UC）和克罗恩病（CD），其特征在于肠粘膜的慢性、不受控制的炎症。目前，美国有多达140万人和欧洲有220万人患有IBD，美国每年报告3万例新病例。不幸的是，IBD无法治愈，需要终生护理。在美国，CD和UC的治疗选择有限，患者通常接受皮质类固醇和免疫抑制药物来缓解症状。然而，鉴于这些药物的毒性和副作用，UC和CD患者迫切需要新的治疗选择。 IBD中胃肠道的炎症由粒细胞和单核细胞介导。IBD的一种令人兴奋的新疗法是基于使用称为粒细胞/单核细胞单采术（GMA）的策略从外周血中选择性地去除这些细胞，具有使患者免于类固醇、减少类固醇依赖性并避免住院和手术的潜力。两种这样的GMA装置在日本和欧洲被批准使用，但它们具有不同程度的特异性和选择性。这导致治疗效果不一致，并增加了不良结局（如血小板减少症或淋巴细胞减少症）的风险。此外，这两种产品都没有被批准在美国使用。Affinergy发现了一种专有的肽，可以与单核细胞和粒细胞结合，但不与淋巴细胞、红细胞或血小板结合。我们已经使用这种肽从全血中选择性地捕获单核细胞和粒细胞，而不捕获其他细胞类型。在该第1阶段应用中，我们将证明该肽可用于开发高选择性和高效的上级GMA装置的概念验证。在第2阶段，我们将使用体内溃疡性结肠炎模型测试我们的设备的有效性，因为我们收集数据以提交给FDA。

DESCRIPTION (provided by applicant): Inflammatory Bowel Disease (IBD), comprised primarily of ulcerative colitis (UC) and Crohn's disease (CD), is characterized by a chronic, uncontrolled inflammation of the intestinal mucosa. As many as 1.4 Million people in the United States and 2.2 Million people in Europe currently suffer from IBD, with 30,000 new cases reported each year in the US. Unfortunately, there is no cure for IBD, which necessitates a lifetime of care. There are limited treatment options for CD and UC in the United States, and patients typically receive corticosteroids and immunosuppressive drugs to alleviate symptoms. However, given the toxicity and side effects of these drugs, there is an urgent need for new treatment options for patients with UC and CD. Inflammation of the gastrointestinal tract in IBD is mediated by granulocytes and monocytes. An exciting new therapy for IBD is based on selectively removing these cells from peripheral blood using a strategy known as granulocyte/monocyte apheresis (GMA), with the potential to spare patients from steroids, reduce steroid- dependency, and avoid hospitalization and surgery. Two such GMA devices are approved for use in Japan and Europe, but they operate with varying degrees of specificity and selectivity. This leads to inconsistent treatment efficacy, and increases the risk of unwanted outcomes such as thrombocytopenia or lymphopenia. Furthermore, neither product is approved for use in the United States. Affinergy has discovered a proprietary peptide that binds to monocytes and granulocytes, but does not bind to lymphocytes, erythrocytes, or platelets. We have used this peptide to selectively capture monocytes and granulocytes from whole blood without capturing other cell types. In this Phase 1 application, we will demonstrate proof-of- concept that this peptide can be used to develop a superior GMA device that is both highly selective and highly efficient. In Phase 2, we will test the efficacy of our device using an in viv ulcerative colitis model as we collect data for a submission to the FDA.