Role of Peripheral Serotonin in Oculocutaneous Albinism
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Level of serotonin and its metabolites in serum
研究概览
简要总结
Serotonin (5-HT or 5-hydroxytryptamine) is a monoamine primarily known for its role as a neurotransmitter in the central nervous system (CNS). However, the functions of serotonin go beyond its role in the central nervous system: different peripheral tissues have the capacity to produce and/or use serotonin locally, forming systems called "micro-serotonergic" systems. Among the peripheral roles of serotonin, previous work by the Iron and Immunity team, INSERM U1016, Institut Cochin (Paris), was able to show that serotonin has a positive role on erythropoiesis and the survival of red blood cells, and the team's ongoing work suggests that serotonin also impacts iron metabolism.
In humans and in mouse models, several studies have suggested a role for serotonin in pigmentation. In certain syndromic forms of albinism such as Hermansky Pudlak syndrome, platelet serotonin levels are reduced in connection with a decrease in dense platelet granules (delta granules): this characteristic is even part of the diagnostic criteria.
Preliminary data from the Iron and Immunity team found:
- Changes in serotonin levels in children with albinism compared to control patients,
- Changes in hemoglobin level and mean corpuscular volume (MCV) in children with albinism (towards anemia and microcytosis),
- Changes in the iron balance in children with albinism (towards iron deficiency).
The hypothesis of this research is that peripheral serotonin plays a role in the clinical and biological manifestations of oculocutaneous albinism.
详细描述
Serotonin (5-HT or 5-hydroxytryptamine) is a monoamine primarily known for its role as a neurotransmitter in the central nervous system (CNS). However, the functions of serotonin go beyond its role in the central nervous system: different peripheral tissues have the capacity to produce and/or use serotonin locally, forming systems called "micro-serotonergic" systems. Among the peripheral roles of serotonin, previous work by the Iron and Immunity team, INSERM U1016, Institut Cochin (Paris), was able to show that serotonin has a positive role on erythropoiesis and the survival of red blood cells, and the team's ongoing work suggests that serotonin also impacts iron metabolism.
Albinism exhibits significant clinical and genetic heterogeneity with poor genotype-phenotype correlation, and nearly 15% of patients remain without a molecular diagnosis. There is no curative treatment for albinism. Patients with albinism suffer from physical disability throughout their lives, but can also suffer from psychological disability and discrimination. These patients are also more vulnerable to the effects of climate change. The unmet clinical needs are therefore enormous.
In humans and in mouse models, several studies have suggested an unexpected role for serotonin in skin pigmentation at several levels. Transcriptomic studies revealed that the Tph1 gene, responsible for serotonin synthesis outside the CNS, as well as serotonin receptors, were expressed in melanocytic and keratinocytic cell lines. Other studies have indicated that serotonin enhances melanogenesis in three melanocyte cell lines (B16F10, SK-MEL-2, Melan-a). Finally, studies suggest that serotonin is involved in pathologies such as certain congenital dyschromias, Rett syndrome and vitiligo. In certain syndromic forms of albinism such as Hermansky Pudlak syndrome, platelet serotonin levels are reduced in connection with a decrease in dense platelet granules (delta granules): this characteristic is even part of the diagnostic criteria.
Preliminary data from the Iron and Immunity team found:
- Changes in serotonin levels in children with albinism compared to control patients,
- Changes in hemoglobin level and mean corpuscular volume (MCV) in children with albinism (towards anemia and microcytosis),
- Changes in the iron balance in children with albinism (towards iron deficiency).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with albinism aged 2 to 17 years
- •Followed in the MAGEC-Necker reference center (reference center for rare diseases of the skin and mucous membranes of genetic origin), during the inclusion period
- •Information of parental authority holders of patients and patients of understanding age, and collection of consent from parental authority holders and patients.
- •Patients aged 2 to 17 years old
- •Having consulted in Necker hospital during the inclusion period in the emergency and surgical services and whose care required a blood test analyzed in the hematology laboratory of the Necker hospital.
- •Normal complete blood count (CBC)
- •Normal C-reactive protein test (CRP)
- •Absence of opposition from parental authority holders within one month of after sending the study information note.
排除标准
- •- Inability to have a blood test
- •Abnormal blood count
- •Elevation of CRP above laboratory standard
结局指标
主要结局
Level of serotonin and its metabolites in serum
时间窗: Day 0
Levels of serotonin and its metabolites in serum in children with albinism, compared with control children.
次要结局
- Correlation between serotonin levels and molecular subtype of albinism(Day 0)
- Correlation between serotonin levels and severity of albinism(Day 0)
- Correlation between serotonin levels and iron studies(Day 0)
- Correlation between serotonin levels and hemoglobin(Day 0)