牵头项目 1：苯丙酮尿症 (PKU)-猫眼课题宝

牵头项目 1：苯丙酮尿症 (PKU)

批准号：

10668618

负责人：

Kiran Musunuru

金额：

$106.93万

依托单位：

CHILDREN'S HOSP OF PHILADELPHIA

依托单位国家：

美国

项目类别：

财政年份：

2023

资助国家：

美国

项目状态：

未结题

起止时间：

2023-08-01 至 2028-07-31

来源：

https://reporter.nih.gov/project-details/10668618

关键词：

Address Adenine Anaphylaxis Animal Model Biodistribution Blood Classical phenylketonuria Defect Diet Dietary Intervention Disease Dose Drug Kinetics Drug Packaging Enzymes Europe Felis catus Funding Genes Goals Guide RNA Hepatocyte High Prevalence Human Hyperphenylalaninaemias Impaired cognition Impairment Inherited Injectable Investigational Drugs Investigational New Drug Application Lead Link Liver Mediating Medical Metabolic Metabolic Diseases Middle East Modeling Mus Mutation Oral Outcome Pathogenicity Patients Pharmaceutical Preparations Pharmacology and Toxicology Phase I/II Clinical Trial Phenotype Phenylalanine Phenylalanine Hydroxylase Phenylketonurias Population Risk Russia Therapeutic Toxic effect United States Food and Drug Administration Variant Work amino acid metabolism autosome base editing base editor causal variant cofactor cognitive development curative treatments enzyme therapy gallium arsenide genome editing humanized mouse lead optimization lipid nanoparticle mutation correction neuropsychiatry neurotoxic neurotoxicity nonhuman primate pharmacologic postnatal pre-Investigational New Drug meeting prenatal prime editing prime editor response therapeutic genome editing transition mutation

项目摘要

项目成果

Kiran Musunuru的其他基金

相似基金

相关文献

中文摘要

翻译

项目总结苯丙酮尿症(PKU)是一种常染色体隐性遗传病，由基因编码突变引起苯丙氨酸羟基酶(PAH)，导致苯丙氨酸(Phe)蓄积到神经毒性水平。在全球最常见的五种致病多环芳烃变异中，c.842C&gt；T(P281L)突变，其受腺嘌呤碱基编辑的影响。目前的治疗方案有很大的局限性-严格的许多患者很难坚持的低Phe饮食，以及每天注射的酶疗法有很大的过敏反应风险。Lead项目1将重点放在基于脂质纳米颗粒(LNP)的腺嘌呤基础上编辑P281L变异患者的PKU治疗，目标是在年底之前提交IND申请五年资助期结束，并在不久之后开始1/2期临床试验。

英文摘要

PROJECT SUMMARY Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the gene encoding phenylalanine hydroxylase (PAH), resulting in the accumulation of phenylalanine (Phe) to neurotoxic levels. Among the five most frequently occurring pathogenic PAH variants worldwide is the c.842C>T (P281L) mutation, which is amenable to adenine base editing. The current treatment options have significant limitations—a strict low-Phe diet to which many patients find it difficult to adhere, and a daily injectable enzyme therapy with a substantial risk of anaphylaxis. Lead Project 1 will focus on a lipid nanoparticle (LNP)-based adenine base editing treatment for PKU in patients with the P281L variant, with the aim to file an IND application by the end of the five-year funding period and begin a phase 1/2 clinical trial soon afterwards.

期刊论文(0)

专著(0)

科研奖励(0)

会议论文