OR ASSOCIATION FUNDS ANOTHER HISTIOCYTOSIS RESEARCH PROJECT IN ARGENTINA.

COLLABORATION AGREEMENT WITH THE PHARMACOLOGY INSTITUTE OF THE FACULTY OF MEDICINE, UNIVERSITY OF BUENOS AIRES, AND THE NATALI DAFNE FLEXER FOUNDATION. 

Since 2014, we have contributed over €130,000 to histiocytosis research, distributed across four studies that we have funded.

OBJECTIVE OF THE COLLABORATION AGREEMENT

To improve the diagnosis and treatment of pediatric and adolescent patients diagnosed with this oncological disease, OR Association is promoting a new research project at the Immunopharmacology Institute of the Faculty of Medicine in Buenos Aires, funded with €10,000 (allocated over two years). This initiative brings together physicians and researchers in the search for new advances and therapeutic targets to deepen our understanding of histiocytosis and potentially achieve effective and safe treatments.

This agreement includes the collaboration of the Natali Dafne Flexer Foundation, a non-profit organization in Argentina with 25 years of experience whose mission is to improve the quality of life of children with cancer. Together, we have co-managed this pioneering project. This is the third agreement signed between the Flexer Foundation and OR Association. Thanks to this partnership, the research institutions have the funds needed to carry out their studies.

FOURTH HISTIOCYTOSIS STUDY FUNDED BY OR ASSOCIATION

The signing of this agreement marks the fourth histiocytosis research project funded by OR Association since 2014.

The first grant was for Langerhans Cell Histiocytosis research at Sant Joan de Déu Hospital in Barcelona: "Early Detection of LCH Neurodegenerative Disease," led by Dr. Vicente Santamaría López.

The second grant was allocated to histiocytosis research at Garrahan Hospital in Buenos Aires (2020): "Immunological Study of Pediatric Patients with Langerhans Cell Histiocytosis," with additional collaboration from the Leo Messi Foundation. The project director is Dr. Guillermo Chantada.

The third grant was provided to the Pathology Laboratory at the Roffo Oncology Institute (2022) for the study "Pathology of Systemic Histiocytic Disorders: Evaluation of Prognostic and Predictive Biomarkers," led by Dr. Erica Rojas Bilbao, the Head of Diagnostic Services.

**PHOTO CAPTION**  
Virtual meeting held in February with the research team to gain an in-depth understanding of their work. Participants: M. Catalina Lava, MD; Guido L. Dalla Vecchia; Prof. Andrea E. Errasti, Ph.D.; E. Antonio Carrera Silva; Denise M. Risnik, Ph.D.; and Fernando Gotz, President of OR Association.

THE IMPORTANCE OF BASIC RESEARCH IN LANGERHANS CELL HISTIOCYTOSIS

Within the Immunopharmacology Laboratory, samples from patients affected by various types of histiocytosis are analyzed. The agreement focuses on financial support for the study "Role of AXL and RANK in the Migration of Pathogenic Cell Precursors to the Bone in Langerhans Cell Histiocytosis."

The principal investigators are Prof. Andrea E. Errasti, Ph.D., E. Antonio Carrera Silva, Ph.D., and Prof. Diego A. Rosso, MD, Ph.D. Team members include M. Catalina Lava, MD; Guido L. Dalla Vecchia, Biochemist; and Denise M. Risnik, Ph.D.

Over the past ten years, the Immunopharmacology Laboratory has conducted numerous scientific studies on histiocytosis, publishing in specialized journals (Blood, 2017; J Immunol., 2022; Clin Immunol., 2024) and presenting at conferences (Annual Meeting of the Histiocyte Society; Argentine Society of Immunology (SAI); Argentine Society of Clinical Research (SAIC)).

THE RESEARCH TEAM

Samples will be provided to the research team by the Pediatric Oncohematology Services at Hospital de Clínicas José de San Martín-UBA and Hospital de Niños Pedro de Elizalde, both located in Buenos Aires.

The Immunopharmacology Laboratory develops research projects in multidisciplinary collaboration with Dr. Diego Rosso, a pediatrician and oncohematologist, who is a leading figure in Argentina and South America in Langerhans Cell Histiocytosis (LCH), and Dr. E. Antonio Carrera Silva, an immunology research specialist from the Institute of Experimental Medicine, IMEX-CONICET-National Academy of Medicine, Buenos Aires, Argentina. Collaborative work began in 2015 to enhance understanding of the pathophysiology of this disease. Describing the underlying mechanisms of inflammatory and/or neoplastic control in LCH could establish a rationale for the use of specific drugs, as well as provide insights into etiopathology and potential new therapeutic targets.

MD. M. Catalina Lava, Physician and Researcher

Dr. Lava is a doctoral student at the Institute of Pharmacology, Faculty of Medicine, University of Buenos Aires, Argentina, and the Institute of Experimental Medicine (IMEX), CONICET, National Academy of Medicine, Buenos Aires, Argentina.

M. Catalina Lava, MD, along with her research team at the Faculty of Pharmacology, University of Buenos Aires, will carry out this study on the role of "homing genes" in the bone pathogenesis of Langerhans Cell Histiocytosis.

**PHOTO CAPTION**  
MD. Catalina Lava during one of her presentations on basic research in histiocytosis.

Treatment and Study of Indomethacin 

This particular study led by Dr. Catalina Lava aims to investigate the effectiveness of indomethacin as a treatment for single or multifocal bone lesions. The objective is to understand the drug’s penetration into bone tissue, the movement of progenitor cells, and their functional behavior.

Indomethacin is an anti-inflammatory drug (NSAID) and is often used as a first, second-line, or even salvage treatment in cases of relapse.

This histiocytosis research project aims to elucidate:  
1. The specific mechanism of action of indomethacin, a low-cost, low-toxicity drug, for the treatment of bone-involved LCH.
2. Whether this mechanism is unique to indomethacin or could extend to other NSAIDs, such as ibuprofen, a widely used pediatric medication.
3. The mechanisms involved in the homing of pathological cells to the bone.
4. New therapeutic targets related to the pathological homing of histiocytes to the bone.

ASSOCIATIONS UNITED FOR THE WELL-BEING OF CANCER PATIENTS

OR Association, based in Barcelona, Spain, firmly believes in providing resources to support research on this disease. This study has been reviewed and approved by the association's Scientific Advisory Committee to ensure the quality of the funded projects. Fernando Gotz Cart, President of OR Association, is convinced that "with the launch of this study, OR Association continues to strive for solutions for curing histiocytosis through research. This research group leading the study has extensive experience in the field of histiocytosis and collaborates with other groups worldwide. Hopefully, this agreement will help us understand this disease, whose etiology (origin) is still unknown."

Natali Dafne Flexer Foundation

Since its establishment in 1994, the Natali Dafne Flexer Foundation has been committed to promoting access for children and young people with cancer in Argentina to appropriate treatment under optimal support and care conditions. The foundation provides free treatment support, emotional care, recreational activities, and informational resources to over 2,800 children with cancer each year. It has nine branches in CABA, Greater Buenos Aires, Tucumán, Corrientes, Chaco, and Jujuy. The foundation also improves hospital infrastructure and equipment, supports the training of healthcare profe