NCT06138509

Peripheral Serotonin and Albinism

Role of Peripheral Serotonin in Oculocutaneous Albinism

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 160 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 2 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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). The hypothesis of this research is that peripheral serotonin plays a role in the clinical and biological manifestations of oculocutaneous albinism. The study will assess serotonin and its metabolites in the serum of patients with albinism, and compare the results with controls patients. The level of serotonin and its metabolites will be correlated with the different genotypes, and with the severity of albinism within the same genotypes. This study also wish to explore the impact of serotonin levels in the development of anemia, microcytosis and/or iron deficiency in patients with albinism. Complete blood counts and iron studies in patients with albinism will be compare to those of control patients too.

Conditions

• Oculocutaneous Albinism

Interventions

Type	Name	Description
OTHER	Dosage of serotonin and metabolites	The dosages of serotonin and its metabolites will be performed by the INSERM U1016 unit at Cochin Institute.
OTHER	Blood parameters	The characterization of blood parameters : complete blood count (CBC), reticulocytes, C-reactive protein (CRP), iron studies (ferritin, serum iron, transferrin and transferrin saturation), hemoglobin electrophoresis, erythropoietin, will be added using standard methods at the Necker hematology laboratory if not carried out as part of the routine care.

Timeline

• Start date: 2024-02-06
• Primary completion: 2026-02-01
• Completion: 2026-02-01
• First posted: 2023-11-18
• Last updated: 2025-09-12

Locations

1 site across 1 country: France