📇 Rhumatologue · QUINCY SOUS SENART · (91) · Hospitalier

M PABLO BARTOLUCCI

Pourquoi vous devez consulter ce praticien

5 raisons identifiées

Plateau technique de référence
Assistance publique – Hôpitaux de Paris (APHP) — équipements et expertise pointus pour les cas complexes
Auteur de référence en rhumatologie
50 articles scientifiques publiés — un praticien à la pointe de la recherche
Encadrant universitaire
Forme la prochaine génération de rhumatologues (3 thèses dirigées)
Disponibilité géographique
2 lieux d'exercice — choisissez celui qui vous arrange
Délais de RDV courts dans la région
73.2 rhumatos / 100 000 hab. — département bien doté

Rhumatologue

📍 QUINCY SOUS SENART (91)HospitalierRPPS 10001597284

Enseignement

📊 Reconnaissance scientifique : 39/100📝 369 articles publiés🇫🇷 Publications académiques françaises (8)🎓 3 thèses dirigées

✨ Génération du profil synthétique IA en cours…

Données ANS publiques (Licence Ouverte 2.0) · Enrichissements MonRhumato 100 % opt-in · Toute personne référencée peut demander la suppression ou la rectification.

Top publications · les plus citées

Sickle cell disease landscape and challenges in the EU: the ERN-EuroBloodNet perspective

The Lancet. Haematology · 2023

📚 29 citations🎯 RCR 5.10Top 8% NIH

Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling

Nature communications · 2023

📚 21 citations🎯 RCR 2.26Top 23% NIH🔓 Open Access📄 PDF gratuit ↗

Lire l'abstract Crossref ↓

AbstractWe previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT 03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT 03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.

Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease

Nature communications · 2025

📚 13 citations🎯 RCR 4.34🩺 Clinique🔓 Open Access📄 PDF gratuit ↗

Lire l'abstract Crossref ↓

Abstract In sickle cell disease (SCD), the β6Glu→Val substitution in the β-globin leads to red blood cell sickling. The transplantation of autologous, genetically modified hematopoietic stem and progenitor cells (HSPCs) is a promising treatment option for patients with SCD. We completed a Phase I/II open-label clinical trial (NCT03964792) for patients with SCD using a lentiviral vector (DREPAGLOBE) expressing a potent anti-sickling β-globin. The primary endpoint was to evaluate the short-term safety and secondary endpoints included the efficacy and the long-term safety. We report on the results after 18 to 36 months of follow-up. No drug-related adverse events or signs of clonal hematopoiesis were observed. Despite similar vector copy numbers in the drug product, gene-marking in peripheral blood mononuclear cells and correction of the clinical phenotype varied from one patient to another. Single-cell transcriptome analyses show that in the patients with poor engraftment, the most immature HSCs display an exacerbated inflammatory signature (via IL-1 or TNF-α and interferon signaling pathways). This signature is accompanied by a lineage bias in the HSCs. Our clinical data indicates that the DREPAGLOBE-based gene therapy (GT) is safe. However, its efficacy is variable and probably depends on the number of infused HSCs and intrinsic, engraftment-impairing inflammatory alterations in HSCs. Trial: NCT03964792

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M PABLO BARTOLUCCI

Pourquoi vous devez consulter ce praticien

Direction de thèses

Activité de recherche & publications

Publications académiques en France

Lieux de consultation(2)

Tarifs & secteur de conventionnement

Prendre rendez-vous & contact

Top publications · les plus citées

Publications scientifiques (50) — classées par pathologie

Transversal36

Génétique5

Essai clinique4

Pharmacovigilance2

Revue générale2

Case report / série1

Épidémiologie & registres1

Revue / méta-analyse1

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