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Prolactin monoclonal antibodies (PRL-mAbs) for the treatment of female-predominant pain syndromes

用于治疗女性为主的疼痛综合征的催乳素单克隆抗体 (PRL-mAb)

基本信息

批准号：
10255683
负责人：
Pierre Riviere
金额：
$ 49.66万
依托单位：
PEPTIDE LOGIC, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10255683
关键词：
Adherence Adverse effects Agonist Animals Antibodies Antibody Therapy Biological Assay Cells Control Animal Data Dose Dysmenorrhea Etiology Exhibits Female Fibromyalgia Filament Freedom Goals Human Human Placental Lactogen Hyperalgesia Immunization In Vitro Injury Intravenous Irritable Bowel Syndrome Logic Migraine Modeling Monoclonal Antibodies Mus Nociception Nociceptors Opioid Pain Pain-Free Peptides Peripheral Phase Phosphorylation Pituitary Gland Prevalence Prevention Prolactin Prolactin Receptor Protein Isoforms Proteomics Quality of life Randomized Recombinants Reporting Research Research Personnel Role Route Safety Signal Transduction Small Business Innovation Research Grant Somatotropin Stat5 protein Subgroup Syndrome Tactile Tail Temporomandibular Joint Disorders Testing Therapeutic Translating Veins Vulvodynia Woman allodynia base blind cabergoline clinical development cross reactivity design digital efficacy study endometriosis experimental study follow-up improved in vitro Assay in vivo male novel prevent programs public health relevance response sexual dimorphism stable cell line standard of care subcutaneous success tissue injury tool tumor

项目摘要

ABSTRACT: Women are disproportionally impacted by functional pain syndromes (FPS), a large subgroup of pain conditions defined by the absence of a clear etiology or tissue injury. These syndromes have a high female:male prevalence ratio and include, but are not limited to, temporomandibular joint and muscle disorders (TMJD) (9:1 ratio), fibromyalgia (9:1 ratio), irritable bowel syndrome (IBS) (3:1 ratio), and migraine (3:1 ratio), as well as female exclusive FPS such as dysmenorrhea, endometriosis and vulvodynia. Reasons for the sexually dimorphic prevalence in FPS remain uncertain but emerging evidence suggests that prolactin (PRL) elicits sensitization of female nociceptors. PRL selectively promotes hyperalgesia and pain in female mice with minimal effects in male animals. PRL signals through mutually inhibitory long- and short-form PRL receptor (PRLR) isoforms that are expressed at higher levels in female nociceptors. Female animals and humans have higher circulating PRL than males. A role for circulating PRL was demonstrated by prevention of opioid-induced hyperalgesia (OIH) selectively in female mice by cabergoline, a dopaminergic D2 agonist which inhibits PRL release from the pituitary. Similarly, migraines associated with PRL-secreting tumors are treated with D2 agonists. Collectively, these data support that PRL selectively promotes female hyperalgesia. Our team now wishes to translate these breakthrough findings into novel and transformative therapeutics for female-prevalent pain conditions. We propose to develop PRL monoclonal antibodies (PRL-mAbs) as first-in- class therapeutics for female FPS, targeting migraine as the primary indication. The specific goals of this SBIR Phase I application are to (i) assess the technical feasibility of the program (i.e., identification of neutralizing PRL-mAb leads) and (ii) validate the working hypothesis (i.e., demonstration that systemic administration of a neutralizing PRL-mAb selectively prevents PRL-induced female hyperalgesia in a migraine relevant model). Impact and

摘要：功能性疼痛综合征（FPS）对女性的影响是不成比例的