Effect of Chinese herbal medicine on food allergy

描述（由申请人提供）：食物过敏在美国是一个日益严重的健康问题。PN或其他食物过敏没有明确的治疗方法。在我们最初的R 01资助项目中，我们开发了食物过敏草药配方-2（FAHF-2），并表明它在小鼠模型中完全阻断了PN诱导的过敏反应，并且具有很高的安全性。保护作用持续至治疗后6个月，与免疫调节作用相关，但与总体免疫抑制无关。这些结果表明FAHF-2是开发治疗食物过敏的植物药的最佳候选药物。我们开始的FAHF-2 I期临床研究已获得FDA IND和IRB批准。在此更新申请中，我们建议研究FAHF-2对食物过敏的持续作用，并研究FAHF-2的免疫机制以及化学和药理学特性。我们将追求两个具体目标来继续这项研究。目标1。研究FAHF-2在食物过敏患者中的安全性和有效性：为此，我们将在12 -45岁年龄组中研究FAHF-2对PN、TN、鱼类和贝类过敏（最严重和慢性食物过敏）的安全性和有效性。我们正在进行一项急性I期研究，随后是一项为期6个月的长期、开放标签扩展研究。在完成这些安全性研究后，我们将进行一项II期双盲、随机、安慰剂对照试验。我们将使用标准方法，如双盲、安慰剂对照口服食物挑战，以评价临床结局，包括长期疗效。我们还将研究免疫调节机制，重点是CD 8 + T细胞产生IFN-3。目标2。精制FAHF-2产品并研究B-FAHF-2的化学和药理学特征：我们目前的IND FAHF-2是一种部分精制但仍凝结的草药产品。我们建议使用丁醇纯化进一步精制该产品，因为丁醇分馏（B-FAHF-2）显著降低了有效日剂量，并且在我们的PNA动物模型中保持了功效。B-FAHF-2可能是分离活性组分的优选起点。我们将使用化学分析（HPLC，质谱和NMR）和生物测定的组合来分离和鉴定B-FAHF-2中的活性成分，然后开始初步的小鼠药代动力学研究。这是第一次临床研究的植物药对多种持续性食物过敏。完成这项研究将是至关重要的，以验证这种中草药在PNA和其他食物过敏的可能临床用途，并了解其作用机制。我们还将能够进一步完善FAHF-2产品，以改善我们的临床研究，并确定活性化合物，以了解这种复杂的植物产品的药理学特征。最终，这项研究可能会导致一个安全有效的草药治疗食物过敏。公共卫生相关性：食物过敏在美国是一个日益严重的健康问题，现在是过敏反应的主要原因;目前，花生或其他食物过敏还没有明确的治疗方法。在我们最初的R 01资助项目中，我们从经典的传统中药配方中产生了食物过敏草药配方（FAHF-2），并在花生过敏的小鼠模型中证明了其有效性，安全性和持久性效果;我们在此更新中建议研究FAHF-2对花生，树坚果，鱼类和贝类过敏的患者年龄在12-45岁，我们已经收到IND批准的植物药计划（IND 77，468）。这将促进中医药治疗的科学知识的发展，以改善食物过敏者的健康，生产力，独立性和生活质量，因此符合2010年健康人的目标，并可能导致安全有效的食物过敏草药疗法。

DESCRIPTION (provided by applicant): Food allergy is a growing and serious health concern in the United States. There is no definitive treatment for PN or other food allergies. In our initial R01 grant project, we developed Food Allergy Herbal Formula-2 (FAHF-2) and showed that it completely blocked PN-induced anaphylaxis in a murine model and had a high safety profile. Protection persisted up to 6 months post therapy, and was associated with immunomodulatory effect, but not overall immune suppression. These results demonstrate that FAHF-2 is an optimal candidate for developing a botanical drug for treating food allergies. We began the FAHF-2 phase I clinical study have obtained FDA IND and IRB approvals. In this renewal application, we propose to investigate the persistent effect of FAHF-2 on food allergy, and investigate the immunotherapeutic mechanisms, and chemical and pharmacological characteristics of FAHF-2. We will pursue two specific Aims to continue this study. Aim #1. Investigate the safety and efficacy of FAHF-2 in food allergy patients: In this aim we will investigate the safety and efficacy of FAHF-2 on PN, TN, fish, and shellfish allergies, the most severe and chronic food allergies, in a12-45 year old age group. We are conducting an acute phase I study, followed by a long-term, open-label extension study of 6 months duration. After completing these safety studies, we will conduct a phase II double-blind, randomized, placebo-controlled trial. We will use standard methods such as double- blind, placebo-controlled oral food challenges to evaluate the clinical outcomes including long-term efficacy. We will also study the immunomodulatory mechanism focusing on IFN-3 production of CD8+ T cells. Aim #2. Refine FAHF-2 product and Investigate chemical and pharmacological characteristics of B-FAHF-2: Our current IND, FAHF-2, is a partially refined, but still curded herbal product. We propose to further refine this product, using butanol purification because butanol fractionation (B-FAHF-2) significantly reduced the effective daily dose and remained efficacy in our animal model of PNA. B-FAHF-2 might be the preferred starting point for isolation of active components. We will use a combination of chemical analysis (HPLC, mass spectrometry and NMR) and bioassays to isolate and identify active components in B-FAHF-2, and then begin preliminary pharmacokinetic studies in mice. This is the first clinical investigation of a botanical drug for multiple persistent food allergies. Accomplishing this study will be of fundamental importance to validate the possible clinical usefulness of this Chinese herbal medicine in PNA and other food allergies, and to understand the mechanisms of action. We will also be able to further refine FAHF-2 product to improve our clinical study, and identify active compounds for the purpose of understanding pharmacological characteristics of this complex botanical product Ultimately, this study may lead to a safe and effective herbal therapy for food allergy. PUBLIC HEALTH RELEVANCE: Food allergy is a growing and serious health concern in the US and is now the leading cause of anaphylactic reactions; at present, there is no definitive treatment for peanut or other food allergies. During our initial R01 grant project, we generated Food Allergy Herbal Formula (FAHF-2) derived from a classical traditional Chinese medicine formula, and demonstrated its efficacy, safety and persistent effect in a murine model of peanut allergy; we propose in this renewal to investigate the safety, efficacy and systemic immunotherapeutic mechanisms of FAHF-2 on peanut, treenut, fish and shellfish allergies of patients ages 12-45, for which we have received IND approval under the botanical drug program (IND77,468). This will foster the development of scientific knowledge of TCM treatment for improving the health, productivity, independence, and quality of life of persons with food allergies and is thus congruent with the goals of Healthy People 2010 and may lead to a safe and effective herbal therapy for food allergy.