Autism Spectrum Disorder Diagnostic/Therapeutic Agent

自闭症谱系障碍诊断/治疗剂

• 批准号: 8832811
• 负责人: Ronald M Burch
• 金额: $ 22.5万
• 依托单位: SPARK2FLAME, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-05 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832811
• 关键词: Affect; American; Antibodies; Antigens; Area; Autistic Disorder; Autoimmune Process; Behavior; Behavioral; Blood; Brain; Cataloging; Catalogs; Cells; Centers for Disease Control and Prevention (U.S.); Child; Clone Cells; Cloning; Collection; Communication; Complex; Control Groups; Data Set; Development; Diagnosis; Diagnostic; Diamond; Disease; Disease susceptibility; Early Diagnosis; Early Intervention; Emotional; Employee Strikes; Family; Female; Fetus; Financial cost; Frequencies; Funding; Goals; Human; Immunoglobulin G; Individual; Institutes; Intellectual Property; Intervention; Laboratories; Language; Lead; Licensing; Link; Medical; Medical Research; Modality; Molecular; Monoclonal Antibodies; Mothers; Mus; Neurodegenerative Disorders; Neurodevelopmental Disorder; Pathologic; Pathway interactions; Phase; Phenotype; Plasma; Population; Prevention; Private Sector; Registries; Relative (related person); Research; Research Personnel; Resources; Risk; Serum; Small Business Innovation Research Grant; Social Interaction; Syndrome; Testing; Therapeutic; Therapeutic Agents; Thinking; Time; Translating; Validation; Voltage-Gated Potassium Channel; Woman; Work; autism spectrum disorder; base; behavioral study; blood resource; clinical practice; cognitive ability; commercialization; expectation; expression cloning; fetal; gender preference; genetic resource; genome wide association study; immune activation; improved; in utero; in vivo; innovation; insight; interest; male; novel diagnostics; novel therapeutic intervention; offspring; polyclonal antibody; pregnant; programs; protein complex; public health relevance; skills; stem; unborn child

DESCRIPTION (provided by applicant): Autism Spectrum Disorder (ASD) is a significant medical problem. ASD affects approximately 1% of the population and extracts enormous emotional and financial costs from the afflicted and their families. Despite years of research we understand very little about the molecular triggers of ASD and preventative therapeutics remain elusive. Recently, maternal immune activation has been gaining acceptance as a likely environmental trigger. Indeed, a growing body of evidence suggests that specific brain-reactive antibodies in women may put their in utero child at risk for ASD. To date, the researchers working in this area have focused on the pathologic activity of serum or polyclonal antibodies isolated from the mothers of an ASD child. Spark2Flame, Inc (S2F) has licensed intellectual property from the Diamond laboratory at The Feinstein Institute for Medical Research ("Feinstein"), who has recently taken this analysis to a new level by cloning individual brain-reactive monoclonal antibodies from mothers of ASD children and demonstrating that, when injected intravenously into pregnant mice, such monoclonal antibodies lead to abnormal brain development and ASD-related behavioral abnormalities in male but not female offspring. This gender preference in mice is especially intriguing in view of the fact that ASD overwhelmingly (nearly 5:1) afflicts male children. Since approximately 10% of mothers of a child with ASD harbor brain-reactive antibodies, we are now poised to use these brain-reactive monoclonal antibodies to advance a commercial ASD diagnostic (and ultimate therapeutic modality) that will identify mothers whose unborn child is at risk for this devastating disorder. The objective of this application is to achieve a realistic proof-of-concept milestone in creating an ASD diagnostic/therapeutic product. We will test our hypothesis and accomplish our objectives of this proposal by pursuing two Specific Aims: 1. Identify those antibodies that alter fetal brain development. 2. Expand the panel of anti-brain monoclonal antibodies obtained from mothers of children with ASD. With the successful completion of these Specific Aims, we will attract further funding from the Federal or private sector. With SBIR Phase 2 funding, we will continue focusing on the ASD diagnostic as well as developing a "decoy antigen" therapeutic approach based on the antibodies that alter brain development. Such an ASD preventative therapeutic offers the advantage that it will be non-immuno suppressive and can be administered during a circumscribed time window.

描述（由申请人提供）：自闭症谱系障碍（ASD）是一个重要的医学问题。ASD影响了大约1%的人口，并从受影响的人及其家庭中提取了巨大的情感和经济成本。 尽管经过多年的研究，我们对ASD的分子触发因素知之甚少，预防性治疗仍然难以捉摸。最近，母体免疫激活已被接受为可能的环境触发因素。事实上，越来越多的证据表明，女性体内的特定脑反应抗体可能会使其子宫内的孩子面临ASD的风险。迄今为止，在这一领域工作的研究人员已经集中在从ASD儿童的母亲分离的血清或多克隆抗体的病理活性。Spark 2Flame，Inc（S2 F）已从范斯坦医学研究所的钻石实验室获得知识产权许可（“Feinstein”），他最近通过从ASD儿童的母亲身上克隆单个脑反应性单克隆抗体，并证明，当静脉注射到怀孕的小鼠体内时，这种单克隆抗体导致雄性后代而不是雌性后代的异常脑发育和ASD相关行为异常。考虑到ASD绝大多数（接近5：1）折磨男孩的事实，小鼠的这种性别偏好特别有趣。由于大约10%的ASD儿童的母亲携带脑反应性抗体，我们现在准备使用这些脑反应性单克隆抗体来推进商业ASD诊断（和最终的治疗方式），以识别未出生的孩子有患这种毁灭性疾病的风险的母亲。的目标 该应用是为了在创建ASD诊断/治疗产品中实现现实的概念验证里程碑。我们将测试我们的假设，并通过追求两个具体目标来实现我们的目标：1。识别那些改变胎儿大脑发育的抗体。 2.扩大从ASD儿童母亲获得的抗脑单克隆抗体组。随着这些具体目标的成功完成，我们将吸引更多来自联邦或私营部门的资金。有了SBIR第二阶段的资助，我们将继续专注于ASD诊断，并开发一种基于改变大脑发育的抗体的“诱饵抗原”治疗方法。这样的ASD预防性治疗提供了这样的优点，即它将是非免疫抑制性的，并且可以在限定的时间窗期间施用。