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Pharmacologic Intervention for Ectopic Calcification

Pharmacologic Intervention for Ectopic Calcification
异位钙化的药物干预
批准号:
10359773
负责人:
Qiaoli Li
金额:
$17.35万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-03-01 至 2024-02-29

项目摘要

项目成果

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中文摘要
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摘要
英文摘要
ABSTRACT This application revolves around ectopic calcification disorders, pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), two autosomal recessive diseases with considerable morbidity and mortality due to calcium hydroxyapatite deposition in the skin, eyes, and the cardiovascular system. There is currently no effective or specific treatment for the ectopic calcification in these disorders. We have developed and characterized mouse models for both PXE and GACI, and these mice now form the platform for preclinical development of therapeutic strategies for these two, currently intractable conditions. The unifying pathological finding in these ectopic calcification disorders is reduced plasma inorganic pyrophosphate (PPi) levels. While significant insight was gained in these disorders, disease mechanism-directed treatment by targeting PPi deficiency prevented new calcification but failed to remove existing ectopic calcification. In this proposal, we will test the overall hypothesis that counteracting ectopic calcification, either by prevention of mineral deposition in the fetus and/or removal of the existing deposits postnatally, will provide treatment approaches with clinical stabilization or cure for patients with PXE or GACI. The therapeutic drug, acetazolamide, has the great potential of counteracting ectopic calcification, primarily due to its physicochemical and cellular mechanisms which are independent of plasma PPi levels. We will specifically focus on two areas of investigation: (a) Prevention of prenatal arterial calcification in GACI by administration of acetazolamide to the mothers during pregnancy, with or without continued treatment of the newborns; this drug will be repurposed from its previous applications to treat various calcification disorders; and (b) We will further focus our efforts to remove existing calcification in PXE and GACI by administration of acetazolamide. These studies will utilize combined prevention and removal approaches to counteract ectopic calcification, providing scientific premise to the investigation. Collectively, our proposed studies will provide critical translational information from preclinical approaches that will allow development of novel treatment for currently intractable disorders PXE and GACI. We also expect that our findings will advance clinical management of ectopic calcification in general, potentially applicable to a number of other diseases, both genetic and acquired.
期刊论文(8)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1016/j.gim.2021.08.011
发表时间: 2022-01
期刊: Genetics in medicine : official journal of the American College of Medical Genetics
影响因子: --
作者: [Saeidian AH, Youssefian L, Huang J, Touati A, Vahidnezhad H, Kowal L, Caffet M, Wurst T, Singh J, Snook AE, Ryu E, Fortina P, Terry SF, Schoenecker JG, Uitto J, Li Q]
通讯作者: Li Q
DOI: 10.1371/journal.pgen.1010192
发表时间: 2022-04
期刊: PLoS genetics
影响因子: 4.5
作者: []
通讯作者:
Functional Assessment of Missense Variants in the ABCC6 Gene Implicated in Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder.
与弹性假黄瘤(一种遗传性异位矿化障碍)有关的 ABCC6 基因错义变异体的功能评估。
DOI: 10.1016/j.jid.2021.08.435
发表时间: 2022-04
期刊: The Journal of investigative dermatology
影响因子: --
作者: [Kowal L, Huang J, Luo H, Singh J, Snook AE, Uitto J, Li Q]
通讯作者: Li Q
DOI: 10.3390/ijms242015041
发表时间: 2023-10-10
期刊: International journal of molecular sciences
影响因子: 5.6
作者: []
通讯作者:
6
    Enzyme Therapy for PXE: Breaking the Barrier of Ectopic Calcification
    • 批准号:
      10527964
    • 项目类别:
    • 资助金额:
      $18.75万
    • 财政年份:
      2022
    • 负责人:
      Qiaoli Li
    • 依托单位:
    Enzyme Therapy for PXE: Breaking the Barrier of Ectopic Calcification
    • 批准号:
      10689263
    • 项目类别:
    • 资助金额:
      $20.95万
    • 财政年份:
      2022
    • 负责人:
      Qiaoli Li
    • 依托单位:
    Novel Treatments for PXE
    • 批准号:
      10162503
    • 项目类别:
    • 资助金额:
      $33.04万
    • 财政年份:
      2018
    • 负责人:
      Qiaoli Li
    • 依托单位:
    Novel Treatments for PXE
    • 批准号:
      10410523
    • 项目类别:
    • 资助金额:
      $33.72万
    • 财政年份:
      2018
    • 负责人:
      Qiaoli Li
    • 依托单位:
    国内基金
    海外基金
    肿瘤微环境因子Lactic acidosis在肿瘤细胞耐受葡萄糖剥夺中的作用机制研究
    • 批准号:
      81301707
    • 项目类别:
      青年科学基金项目
    • 资助金额:
      23.0万元
    • 批准年份:
      2013
    • 负责人:
      吴昊
    • 依托单位: