Generation of Powerful Biological Tools - Fibroblast or Inducible Pluripotent Bone Marrow Cells - for Understanding the Pathophysiology of Chronic Granulomatous Disease.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- to study the impact of protein deficits Nox2 and p22phox, in the physiopathology of neurons from inducible pluripotent bone marrow cells (iPSC)
研究概览
简要总结
Chronic granulomatous disease (CGD) is a rare genetic disease of innate immune due to the malfunction of phagocytic cells unable to destroy pathogens during infection. The four genes implicated are CYBB, CYBA, NCFA and NCF2 respectively encoding Nox2, p22phox, p47phox and p67phox. Nox2 analogs have recently been discovered in cells other than phagocytes. So the question arises on physiopathological impact of the absence of theses proteins not only in phagocytes but also in other cells types such as fibroblasts or neurons.
The principal objective is thus to study the impact of protein deficits Nox2 and p22phox, in the pathophysiology of neurons from inducible pluripotent bone marrow cells (iPSC).
For this purpose, a collection was built of fibroblasts and keratinocytes from patients with different forms of CGD to get iPSC similar to embryonic marrow cells and differentiable into several cell types (neurons, phagocytes).
详细描述
Non randomised pilot descriptive multicentric study. Since recently it has been shown that Nox2p22phox protein is expressed not only in phagocytic cells but also in non-phagocytic cells such as fibroblasts, epithelial cells ,vascular cells, neurons. If pathological consequences of the deficiency Nox2 and p22phox, essential to the production of bactericidal toxic derivatives at the level of phagocytic cells, is well documented, impact of their absence in other types of non-phagocytic cells is not known. A better understanding of the impact of the absence of these proteins in these tissues could improve the management of CGD patients by providing a more specific monitoring of their condition. Similarly the formation of different cell models of all genetic forms of CGD that do not exist at present will be of great use to study the physiopathology of this disease and as tools for future studies.
The study requires the inclusion of minor subjects as CGD is usually diagnosed in early childhood ( <2 years), it is rare (frequency 1/200 000) and the life expectancy is reduced.
To elaborate the cells collection, hair and skin biopsy are necessary. They will be performed under local anesthesia for adults, and during a planned general anesthesia for minors.
Fibroblasts and keratinocytes in culture will be obtained by conventional control methods and the absence of expression of p22phox or Nox2 will be checked.
Measurement of the kinetics of neuronal development and apoptosis iPSC will be performed in a differentiation system 2 dimensions on stromal cells MS5. For that, markers of neuronal differentiation of each step will be measured.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnostic of chronic granulomatous disease (CGD) with determined genetic form
- •for minors, patient requiring installation or removal of deep venous general anesthesia.
排除标准
- •patients with acute infections scalable to practice of skin biopsy under local anesthesia
- •patient with impaired hemostasis acquired (drug) or innate.
结局指标
主要结局
to study the impact of protein deficits Nox2 and p22phox, in the physiopathology of neurons from inducible pluripotent bone marrow cells (iPSC)
时间窗: one year
measurement of the kinetics of neuronal differentiation and identification of subtypes cell formed
次要结局
- Constitute cellular models of different types of CGD for future physiopathological studies and therapeutic trials(for years)
- To study the impact of protein deficits Nox2 and p22phox , at the physiology of fibroblasts and their transformation into myofibroblasts(two years)
- To study the impact of protein deficits Nox2 and p22phox on cytochrome b558 synthesis process of phagocytes from inducible pluripotent bone marrow cells ( iPSC ).(6 months)