Press releases

Discovery of a future therapy for hemoglobinopathies

26 Apr 2018 | By Inserm (Newsroom) | Genetics, genomics and bioinformatics

©Inserm/Féo, Claude

With the genome editing CRISPR-case.9 technique, researchers at INSERM, the hospital Necker Children-AP-HP, and Université Paris Descartes in the Institute Imagine managed to reactivate a gene that may improve the appearance of red blood cells of patients with hemoglobinopathies such as sickle cell anemia and beta-thalassemia. The teams Annarita Miccio, Inserm researcher, Prof. Marina Cavazzana AP-HP and Isabelle André-Schmutz, Inserm researcher show this new avenue of research and treatment of β -hémoglobinopathies in the journal Blood .

Millions of people are affected by severe forms of these diseases worldwide. They are characterized by an alteration in the expression of the gene encoding the β-globin: an essential component of hemoglobin . These changes can lead to a failure of expression of the β-globin gene, as in the case of β-thalassemia, or by an aggregation of hemoglobin into fibrils leading to the deformation of the red blood cells, in the case of sickle cell disease.

The laboratory Annarita Miccio, Inserm researcher, was particularly interested in the reactivation mechanisms of fetal hemoglobin . This hemoglobin is unusual act, instead of β-globin, other globin, γ-globin called, which is only expressed during fetal development.

Most patients suffering from β-hemoglobinopathies have a non-altered form of the gene encoding this protein. Its reactivation in patients with thalassemia and sickle cell would replace β-globin mutated γ-globin. This change would result in a significant improvement in the observed state of red blood cells for these diseases and thus associated symptoms (pain associated with vaso-occlusive crises in sickle-cell anemia or correction of anemia in both diseases).

The results show that certain genetic sequences responsible for blocking the expression of globine- γcan be modified, including a DNA sequence which inhibits the production of globin γ after fetal development. Its removal, using “genetic scissors” CRISPR / case.9, reactive synthesis globine- γ at levels sufficient to be considered in the future treatment protocol.

This study also improves the state of knowledge on the expression regulation mechanism to β globin γ during our development.

It also contributes to developing curative therapeutic protocols for these diseases with the majority of current treatments remain symptomatic and very heavy for patients.

In figures  :

Beta-thalassemia and sickle cell disease affect alone nearly 100 million healthy carriers or sick people in the world. 60,000 new cases of β-thalassemia and sickle cell 300,000 are diagnosed annually worldwide.

Besides the high mortality observed, the less severe forms greatly affect the quality of life of these patients and their management represents a very significant cost to health systems.

In developing countries where these diseases have the highest incidence, β-hemoglobinopathies are a major public health issue.

Beta-thalassemia :

– 90 million people affected worldwide, about 288 000 patients

– 60,000 new cases diagnosed each year.

Vichinsky EP: Changing patterns of thalassemia worldwide. Ann NY Acad Sci 2005, “Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia”

Alexis A. Thompson, et al.


– 43 million people in the world carrying the S allele moderately affected. Global Burden of Disease Study 2013, Collaborators (22 August 2015), The Lancet.

– 4.4 million homozygous patients worldwide, so very sick . GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016), The Lancet.

– newborns diagnosed sickle 300,000 worldwide each year.

– 114,000 deaths worldwide in 2015. GBD 2015 Mortality and Causes of Death, Collaborators. (October 8, 2016), The Lancet.

Researcher Contact
Annarita Miccio Chercheuse Inserm U1163 IHU IMAGINE rf.mresni@oiccim.atiranna
Press Contact
Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human β-globin locus, Chiara Antoniani, Vasco Meneghini, Annalisa Lattanzi, Tristan Felix, Oriana Romano, Elisa Magrin, Leslie Weber, Giulia Pavani, Sara El Hoss, Ryo Kurita, Yukio Nakamura, Thomas J. Cradick, Ante S. Lundberg, Matthew Porteus, Mario Amendola, Wassim El Nemer, Marina Cavazzana, Fulvio Mavilio and Annarita Miccio Blood