Dataset Information

In utero Therapy for the Treatment of Sickle Cell Disease: Taking Advantage of the Fetal Immune System.

ABSTRACT: Sickle Cell Disease (SCD) is an autosomal recessive disorder resulting from a ?-globin gene missense mutation and is among the most prevalent severe monogenic disorders worldwide. Haematopoietic stem cell transplantation remains the only curative option for the disease, as most management options focus solely on symptom control. Progress in prenatal diagnosis and fetal therapeutic intervention raises the possibility of in utero treatment. SCD can be diagnosed prenatally in high-risk patients using chorionic villus sampling. Among the possible prenatal treatments, in utero stem cell transplantation (IUSCT) shows the most promise. IUSCT is a non-myeloablative, non-immunosuppressive alternative conferring various unique advantages and may also offer safer postnatal management. Fetal immunologic immaturity could allow engraftment of allogeneic cells before fetal immune system maturation, donor-specific tolerance and lifelong chimerism. In this review, we will discuss SCD, screening and current treatments. We will present the therapeutic rationale for IUSCT, examine the early experimental work and initial human experience, as well as consider primary barriers of clinically implementing IUSCT and the promising approaches to address them.

SUBMITTER: Cortabarria ASV

PROVIDER: S-EPMC7862553 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

<i>In utero</i> Therapy for the Treatment of Sickle Cell Disease: Taking Advantage of the Fetal Immune System.

Cortabarria Alba Saenz de Villaverde ASV Makhoul Laura L Strouboulis John J Lombardi Giovanna G Oteng-Ntim Eugene E Shangaris Panicos P

Frontiers in cell and developmental biology 20210122

Sickle Cell Disease (SCD) is an autosomal recessive disorder resulting from a β-globin gene missense mutation and is among the most prevalent severe monogenic disorders worldwide. Haematopoietic stem cell transplantation remains the only curative option for the disease, as most management options focus solely on symptom control. Progress in prenatal diagnosis and fetal therapeutic intervention raises the possibility of <i>in utero</i> treatment. SCD can be diagnosed prenatally in high-risk patie ...[more]

PMID: 33553164

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Project description:IntroductionNeonates with cardiorespiratory compromise at delivery are at substantial risk of hypoxic neurologic injury and death. Though mitigation strategies such as ex-utero intrapartum treatment (EXIT) exist, the competing interests of neonatal beneficence, maternal non-maleficence, and just distribution of resources require consideration. Due to the rarity of these entities, there are few systematic data to guide evidence-based standards. This multi-institutional, interdisciplinary approach aims to elucidate the current scope of diagnoses that might be considered for such treatments and examine if treatment allocation and/or outcomes could be improved.MethodsAfter IRB approval, a survey investigating diagnoses appropriate for EXIT consultation and procedure, variables within each diagnosis, occurrence of maternal and neonatal adverse outcomes, and instances of suboptimal resource allocation in the last decade was sent to all North American Fetal Treatment Network center representatives. One response was recorded per center.ResultsWe received a 91% response rate and all but one center offer EXIT. Most centers (34/40, 85%) performed 1-5 EXIT consultations per year and 17/40 (42.5%) centers performed 1-5 EXIT procedures in the last 10 years. The diagnoses with the highest degree of agreement between centers surveyed to justify consultation for EXIT are head and neck mass (100%), congenital high airway obstruction (90%), and craniofacial skeletal conditions (82.5%). Maternal adverse outcomes were noted in 7.5% of centers while neonatal adverse outcomes in 27.5%. A large percentage of centers report cases of suboptimal selection for risk mitigation procedures and several centers experienced adverse neonatal and maternal outcomes.ConclusionThis study captures the scope of EXIT indications and is the first to demonstrate the mismatch in resource allocation for this population. Further, it reports on attributable adverse outcomes. Given suboptimal allocation and adverse outcomes, further examination of indications, outcomes, and resource use is justified to drive evidence-based protocols.

Dataset Information

In utero Therapy for the Treatment of Sickle Cell Disease: Taking Advantage of the Fetal Immune System.

Publications

<i>In utero</i> Therapy for the Treatment of Sickle Cell Disease: Taking Advantage of the Fetal Immune System.

Similar Datasets

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