Prof. Marina Cavazzana, pioneer in gene therapy and committed woman

The first glance exchanged with Prof. Marina Cavazzana would bring to light all the dynamism, energy and willpower of this doctor-researcher. And from her willpower, she is now internationally recognized as the pioneer of gene therapy. “The success of the first clinical trials convinced me that I absolutely had to get past the restrictions met and continue my research to benefit young patients” explains Prof. Marina Cavazzana.

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Gene therapy: hope for genetic diseases

Gene therapy is the dream for patients with genetic diseases as it replaces the “sick” gene with a healthy gene. In reality it is a lot more complex that it seems. As the first clinical trials in children with X-linked severe combined immunodeficiency showed in 1999, that she conducted with Prof. Alain Fischer and Prof. Salima Hacein-Bey-Abina (Inserm Unit 768 Normal and pathological development of the immune system”, Biological Therapy Department and Pediatric Hematology and Immunology Unit, Necker-Enfants Malades hospital AP-HP, Paris Descartes University, Paris). Even though they showed the efficacy of this innovative treatment for the first time, they also uncovered faults that have to be resolved. Since, the treatment has continued to improve and it is now used for other diseases.

“Repairing” genes

“Gene therapy can be done in vivo directly into the patient’s body. This approach is favored in central nervous system, neuromuscular or metabolism diseases, describes the professor. As a specialist of blood diseases, the approaches that I have developed with my team take place ex-vivo.” At first, bone marrow stem cells, the cells capable of generating all cell lines in the blood, are taken. Before reinjecting them into the patient, a functional gene is introduced into the cells to make up for the defective gene. “With this approach, we have recently been able to cure children with two forms of genetic anemia: sickle-cell anemia and beta-thalassemia”, rejoices Marina Cavazzana. Patients treated with gene therapy now produce enough hemoglobin and no longer need transfusions.

Discovering other avenues

“In theory, gene therapy could be offered to all patients with genetic disease, she continues, although I am aware that this will not be possible. Research must therefore continue to develop other therapeutic approaches.” And the one for which the conviction is greater than the restrictions against gene therapy already has different leading avenues to reduce transplant rejections from partially compatible donors among other things. As in this case, the chances of success do not exceed 50%, and can reduce to 30% sometimes, against 90% with a compatible family donor.

In this fight, she emphasizes the importance of being at Imagine: it is an accelerator for my work, she explains. My team has the most advanced technologies but also a multidisciplinary network of researchers and doctors around them. She hopes that gene therapy trials soon emerge in other diseases such as myopathies.

To treat the patient more and more, the hematology professor launches a new challenge: to encourage future generations of doctors in all specialties to be creative and go beyond what they are taught to develop the innovative therapies of tomorrow.

Being at Imagine: it is an accelerator for my work
 

Prof. Marina Cavazzana

The fight of a committed woman

Indeed, there is still a lot to explore to reduce genetic diseases and it is by breaking down the walls that new solutions will emerge tomorrow, and this does not just concern treatments: according to her, reducing the isolation of teenagers being cared for also has to be done, by using means of communication that are more appropriate for these generations.

2012 winner of the Irène Joliot-Curie prize awarded by the French Ministry of Research, she lives up to the title of scientific woman of the year and does not stop deploring the under-representation of women in science and medicine. In her laboratory, some simple rules ensure that it is a fair place for everyone: no meeting after 5pm, arranging working times for women with young children, protection regarding comments or attitudes of other colleagues that are uncalled for, support until a position is secured. That also is about breaking down the wall of silence towards the abuse of power, she recalls.

Marina Cavazzana is fighting and applying to herself the motto that she feels so strongly about: do not lose heart and never give up.

 

Marina Cavazzana is a hematology professor at Paris Descartes University, head of the Biological Therapy Department and the Biotherapy Clinical Investigation Center at the Necker-Enfants Malades hospital, AP-HP and co-director of the Inserm Human Lymphohematopoiesis Laboratory at the Imagine Institute of genetic diseases, Paris, France.

 

Son nouveau combat pour un dépistage néonatal de la drépanocytose

Parmi les derniers engagements de Marina Cavazzana figure le dépistage néonatal généralisé de la drépanocytose et ce, afin de prévenir la survenue de manifestations et de complications graves de ce de cette pathologie, la plus fréquente des maladies génétiques.

Le dépistage néonatal est aujourd’hui proposé dans la population générale uniquement dans les départements d’outre-mer. En France métropolitaine, il est restreint aux nouveau-nés à risque, soit ceux dont les parents sont originaires de régions à risque.

Lors d’une étude effectuée entre février et mai 2017 par Marina Cavazzana en collaboration avec le service de genetique du Pr Munnich et l'ADPHE dirigé par le Pr M.Pollack, ce dépistage ciblé  s’est révélé inadapté : en effet sur les 48 143 nouveau-nés testés – 31 405 issus de la population ciblée t 16 778 de celle non-ciblée, 61 enfants atteints de drépanocytose ont été dépisté dont 5 dans la population-non ciblée. A cela s’ajoute les 1588 enfants porteurs d’une mutation d’un seul gène et ne développant pas la maladie (car pour cela les deux gènes celui issu de la mère et celui issu du père doivent être mutés) mais pouvant la transmettre à leur descendance et dont 155 sont issus de la population non-ciblée. « Au-delà de démontrer la pertinence d’étendre le dépistage néonatal de la drépanocytose à l’ensemble de la population, cette étude pointe du doigt le besoin d’informations des professionnels de santé et des sujets hétérozygotes (NDLR porteurs d’une mutation d’un seul gène), » souligne la professeure.

D’ailleurs elle vient de publier une étude qui évalue trois manières différentes de fournir des informations aux parents qui risquent d'avoir un enfant atteint de drépanocytose. « Une meilleure information devrait permettre d’augmenter le taux de dépistage parental et parallèlement de diminuer le nombre de nouveaux cas par an en France », explique-t-elle. Il s’avère que l’envoi d’une lettre suivie d'un appel téléphonique ou de trois SMS est plus efficace qu'une lettre seule pour informer les parents qui risquent d'avoir un enfant atteint de drépanocytose. « Il s’agit désormais d’informer et former tous les professionnels de santé concernés en vue de la la mise en œuvre effective de ce programme, » enchaîne-t-elle.

En complément, elle a également validé un test rapide sur goutte de sang qui pourrait être mis à disposition de tous les cabinets de ville.

« Tout est en place pour généraliser le dépistage néonatal de la drépanocytose, c’est désormais au pouvoir public de passer à l'acte car elle a eu l'occasion de saisir sur ces chiffres préoccupantes l'HAS et le Ministère de la Santé » conclut-elle.

 

Marina Cavazzana est professeure d’hématologie à l’Université Paris-Descartes, cheffe du département de Biothérapie et du Centre d’Investigation Clinique de biothérapie de l’Hôpital Necker-Enfants malades, AP-HP et co-directrice du laboratoire de Lymphohématopoïèse humaine Inserm à l’Institut des maladies génétiques Imagine, Paris, France.