Preclinical therapeutics for sickle cell disease: modern developments and future considerations

Area of Science:

• Hematology
• Genetics
• Pharmacology

Background:

• Current sickle cell disease (SCD) treatments are largely disease-modifying, not curative.
• There is a significant need for therapies that effectively manage SCD complications and improve patient quality of life.

Purpose of the Study:

• To review emerging preclinical therapeutics for sickle cell disease (SCD).
• To discuss the potential impact and future directions of novel SCD interventions.

Main Methods:

• Literature search of Medline, PubMed, and other sources (dated 2025 backward).
• Focus on preclinical therapeutics, excluding established treatments like hydroxyurea.

Main Results:

• Emerging therapies include HbF inducers, pyruvate kinase activators, anti-selectin P monoclonal antibodies, allosteric Hb modifiers, and gene therapy.
• Multimodal therapy and proactive treatment of cerebral artery conditional blood velocity are highlighted for stroke prevention.

Conclusions:

• Preclinical research is crucial for developing curative and disease-modifying SCD interventions.
• Accessibility of these advanced therapies in high-prevalence regions remains a challenge.
• Recent advancements, including gene therapy, offer realistic hope for improved SCD care.