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Protein misfolding in hemophilia
Bilgimol Chumappumkal Joseph1, Juan A De Pablo-Moreno2, Nicca Falah1
1Division of Hematology/Oncology, Department of Medicine, University of California San Diego, La Jolla, CA, United States.
Advances in Protein Chemistry and Structural Biology
|November 27, 2025
Summary
Hemophilia therapy has advanced from contaminated products to gene editing. Current treatments include gene therapy and novel small molecules, with gene editing offering curative potential for Factor VIII and IX deficiencies.
Area of Science:
- Hematology
- Genetics
- Pharmacology
Background:
- Hemophilia A (FVIII deficiency) and B (FIX deficiency) are inherited bleeding disorders caused by F8/F9 gene mutations.
- Mutations lead to misfolded Factor VIII/IX proteins, causing bleeding and joint damage.
- Diagnosis relies on assays measuring factor activity and protein levels.
Purpose of the Study:
- To review the evolution of hemophilia therapies.
- To highlight current and emerging treatment strategies.
- To emphasize the potential of gene editing for hemophilia cure.
Main Methods:
- Review of historical and current hemophilia treatment modalities.
- Analysis of diagnostic approaches for hemophilia A and B.
- Exploration of ongoing research in small molecule therapies and gene editing.
Main Results:
- Therapeutic advancements include recombinant factors, non-factor agents, and gene therapies.
- Gene therapy offers sustained factor levels, reducing prophylactic treatment needs.
- Emerging therapies focus on molecular chaperones, protein stabilizers, and CRISPR/Cas9 gene editing.
Conclusions:
- Hemophilia treatment has progressed significantly, with gene therapy and gene editing showing great promise.
- Future research aims for curative solutions through advanced molecular and genetic interventions.
- Patient adherence and active participation are crucial for effective hemophilia management.
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