Dr. Melissa Bou Jaoudeh
Validation of a humanized mouse model to assess the therapeutic potential of IdeS in hemophilia A with inhibitors’
I am an early research scientist registered as a third-year Ph.D. student at Sorbonne University with a Fellowship from the doctoral school 394 'Physiology, Pathophysiology, and Therapeutics,' working under the supervision of Dr. Sébastien Lacroix-Desmazes. My doctoral research focuses on two aspects of Hemophilia A (HA) treatment: the first is to understand the role of FVIII-containing immune complexes in the induction of immune tolerance in HA, and the second is to investigate the potential use of the IgG-degrading enzyme, IdeS, from Streptococcus pyogenes as a new tool in the treatment of inhibitor-positive HA patients. I am an immunologist with a Master's degree in Sciences, Technologies, and Health from Sorbonne University and a Bachelor's degree in Life and Earth Sciences from Lebanese University's Faculty of Science. The work I performed during my Ph.D. has been presented regularly at international conferences including ISTH, BIC, and EAHAD.
The development of neutralizing anti-factor VIII (FVIII) antibodies is the major drawback of replacement therapy in people with congenital hemophilia A (PwHA), rendering further infusions of FVIII ineffective. These antibodies can also occasionally appear in non-hemophiliacs, such as elderly patients, causing drop in FVIII levels and severe hemorrhagic syndromes. It is referred to as acquired hemophilia A (AHA). In the presence of anti-FVIII antibodies, also known as FVIII inhibitors, bypassing agents (BPA) and/or non-factor replacement therapies are used. In contrast to FVIII replacement therapy, some of these treatments lack predictive biomarkers of hemostatic efficacy and may be responsible for thrombotic accidents, especially in patients with comorbidities.
As an immune escape mechanism, Streptococcus pyogenes, a human pathogen, produces an IgG-degrading enzyme (IdeS). IdeS, also known as Imlifidase, is approved for hyperimmune patients undergoing renal transplantation. It was also used to optimize gene therapy in a pre-clinical model complicated by the presence of anti-AAV neutralizing antibodies.
This work aims to investigate the ability of IdeS to eliminate FVIII inhibitors and open a therapeutic window for the use of FVIII in people with congenital or acquired hemophilia A with inhibitors.