STOCKHOLM — The treatment landscape for sickle cell disease (SCD) is evolving rapidly, with new drugs and gene-based therapies offering a realistic prospect of cure. For most patients, however, particularly in low- and middle-income countries (LMICs), access to these innovations remains a major challenge if not a distant dream. The present and future of SCD treatment were explored in depth at an educational session during the European Hematology Association 2026 Congress. Erfan Nur, MD, PhD, clinical hematologist, Amsterdam University Medical Center, chaired the session.

There are many unmet needs in SCD today, Nur told Medscape News Europe. Among the most important are readily available diagnostic tools to identify the disease, robust awareness campaigns to support prevention in LMICs, tools to gauge disease severity objectively and predict complications, widespread access to "basic" therapies such as hydroxyurea and antibiotics, and financial support for SCD research, he said. “New developments in curative therapies are promising: besides new approaches in gene editing and therapy, important progress has been made in the field of allogeneic hematopoietic stem cell [HSC] transplantation.” 

At the Forefront of Innovation

Annarita Miccio, PhD, director of the laboratory of chromatin and gene regulation during development at the Imagine Institute of genetic disease in Paris, updated attendees on in vivo gene editing, which she called one of the most innovative approaches to treating SCD. The strategy directly targets HSCs in the bone marrow or in circulation and uses gene editing, base editing, and CRISPR/Cas9 to correct the disease-causing mutation or restore expression of fetal hemoglobin (HbF). A range of viral and nonviral vectors (including adenoviral vectors, retroviral vectors, and nanoparticles) deliver gene-editing tools to the target site. Each has its own advantages and limitations. 

Miccio identified the following key characteristics to weigh when evaluating a delivery method for in vivo gene therapy targeting HSCs: efficient editing, specificity, low immunogenicity and inflammation, transient expression of gene-editing tools, and simple manufacturing. Drawing on findings from multiple studies, she examined how well these vectors meet the requirements of an ideal gene-editing vector.

Adenoviral vectors show high editing efficiency upon selection with a low dose of chemotherapeutic agents and relatively simple manufacturing, and researchers are improving their targeting and immune profile. Retroviral vectors have moderate editing efficiency, high specificity, and complex manufacturing, while nanoparticles are efficient and easy to manufacture, though their specificity and potential toxicity remain key challenges. “We need to go back to the pathophysiology of the disease and refocus on the bone marrow niche. We know that in SCD, the bone marrow environment is characterized by inflammation, which may affect HSC targeting in in vivo gene-editing approaches,” Miccio said.

Alongside in vivo gene-editing approaches, the development of novel small molecules designed to promote HbF production represents an important strategy in the evolving SCD treatment landscape. "In the development of these new small molecules, hydroxyurea remains the benchmark because it is the most effective HbF inducer currently available for patients with SCD. It serves as the reference compound against which any new HbF-inducing agent should be compared," said Lucia De Franceschi, MD, professor of internal medicine at the University of Verona, Italy, who reviewed the current state of the art of these compounds.

She classified these agents into three categories: epigenetic modulators, agents involved in the displacement or suppression of gamma-globin gene regulators, and small-molecule modulators of cell-signaling pathways. As she noted in her concluding remarks, the identification and development of lead compounds have relied on several complementary strategies. These include optimizing known HbF inducers (e.g., NDec), drug repurposing (e.g., panobinostat), discovering novel compounds through computational screening and structure-based drug design, and identifying new molecules with innovative mechanisms of action linked to physiologic protein-degradation pathways (e.g., BMS-986470). 

“This area can have a big impact worldwide, and this approach has the potential to be more widely available than the gene therapies,” Nur told Medscape News Europe.

Therapies Through a Global Lens

Roughly 90% of all births affected by SCD occur in sub-Saharan Africa and India, and the number of patients with the disease in Africa is close to 6 million. These figures were presented by Thomas N. Williams, MBBS, PhD, professor of hemoglobinopathy research at Imperial College London, during the third part of the session, which sought to broaden the discussion beyond Europe and the United States to focus on LMICs. Williams, who participates in the KEMRI-Wellcome Research Programme, noted that two decades ago, SCD was a neglected disease in the region, where healthcare priorities lay elsewhere. The situation has improved considerably in recent years, he said: Childhood mortality has fallen dramatically, from around 10% to about 2%-3% in many countries, suggesting that SCD is gaining greater recognition and visibility.

When it comes to treatment, however, the situation remains highly challenging. Gene therapies (along with bone marrow transplantation, transfusion programs, and newer or repurposed drugs) are often unavailable because of logistical barriers and high costs. In this context, early diagnosis and infection prevention remain two cornerstones of care. Together with education of the public and healthcare professionals, and the use of widely available, inexpensive interventions such as antimalarial prophylaxis, penicillin, and vaccines, this approach can make a profound difference for many children, helping to shift outcomes from 90% mortality to 90% survival. 

“The interest in LMICs is increasing but still not significant,” Nur told Medscape News Europe. He called for large-scale collaboration among bodies such as the World Health Organization, the European Union, and large nongovernmental organizations. He also underscored the importance of political commitment from local governments.

Nur, Miccio, and Williams reported no relevant financial relationships. De Franceschi has served on advisory boards for Roche, Sanofi, and Pfizer and has received research grants from Agios and Bristol. 

Cristina Ferrario is a molecular biologist and former researcher in molecular oncology at three institutes in Milan, Italy. She has a master's degree in communication and health from the University of Milan and a master's degree in cancer genetics from the University of Pavia. She has worked as a science journalist for more than 20 years.