Cell and Gene Therapies for Hemophilia: Achievements and Challenges

When:  Sep 13, 2024 from 09:00 to 10:00 (PT)

Contact

Sam Baker
778 945 9922
sam@isctglobal.org


Cell and Gene Therapies for Hemophilia: Achievements and Challenges

Presented by the ISCT Gastro-Intestinal Committee

 

Hemophilia is an inherited bleeding disorder characterized by the deficiency or absence of clotting factors VIII (Hemophilia A) or IX (Hemophilia B). This lack of clotting factors leads to uncontrolled bleeding, which can result in severe health issues, particularly in the joints and brain. Despite significant advances in preventing bleeding episodes and managing the disease through prophylaxis and non-factor products, several needs remain unmet. One critical issue is the lack of a cure for the disease. This challenge is being strategically addressed through the development of innovative cell and gene therapies. The objective of this webinar, led by two eminent researchers, Dr. Edward Tuddenham (UK) and Dr. Blair Gage (Canada), is to discuss the latest advances and challenges associated with the use of both therapies in treating Hemophilia A and B.  Their goal is to achieve a durable reduction in both bleeding risks and the need for exogenous factor administrations. 


Key Learning Objectives: 
  • Discuss collaborations and engaging Chinese researchers with ISCT.
  • Learn on strategies forecasting the development and clinical application of CGT.
  • Increase the knowledge and education on the clinical development of CGT.
  • Showcase hemophilia as significant case example for the evaluation of emerging CGT.
  • Understand the science of CGT development for hemophilia.


Co-Chairs:

Adriana Migliorini, PhD

Senior Post Doctoral Research Fellow

Mc Ewen Stem Cell Institute

University Health Network

Canada

Dr. Adriana Migliorini is a senior postdoctoral research fellow in Dr. Maria Cristina Nostro’s laboratory, at the McEwen Stem Cell Institute, University Health Network, Toronto, Canada. She studied medical biotechnology at the University of Florence (Italy) and completed her Ph.D. in human biology, at the Ludwig Maximilian University in Munich, Germany. Her research primarily revolves around the field of human pluripotent stem cells (hPSCs) and developmental biology, with a specific focus on the pancreas. Her current work involves investigating the composition and phenotype of the fetal pancreatic immune niche to gain a deeper understanding of its role during endocrine development and to explore novel applications for the treatment of Type 1 Diabetes (T1D).

Mustapha Najimi, PhD

Director of Research

UCLouvain

Belgium

Mustapha Najimi is director of research at the institute of Experimental and Clinical Research (IREC) of the Faculty of Medicine and Pharmacy-UCLouvain in Brussels. He holds a PhD in cell and molecular biology from the Pierre & Marie Curie University, Paris in 1999. He joined the team of Pr Etienne Sokal in 2003 to set up a platform of liver cells’ culture dedicated to the development of a clinical cell therapy program. Since then, he led the stem cell group and coordinated the cell culture technology platform of the laboratory of pediatric hepatology and cell therapy. Thanks to an accumulated know-how and significant knowledge of human liver cells’ biology as well as the strategies to isolate them, his research activity led to the discovery of a population of liver mesenchymal progenitor cells. Those cells were the subject of more than 40 international publications, more than 200 citations and the attribution of 7 related patents. Mustapha NAJIMI has actively been/is involved in i) the design and supervision of the large-scale production of the first batches of these progenitor cells, that have been infused to patients with liver diseases at Saint-Luc hospital- Brussels, ii) the technology transfer of this cell therapy product to a spinoff company, iii) the supervision of R&D activities related to those cells with an industrial vision. Thanks to an active network of international collaborations, he continues conducting his research investigations with the major objectives of better understanding the mechanisms governing liver regeneration and improving the use of cell therapy for liver defects.









Speakers:

Blair Gage, PhD

Scientist, Assistant Professor

Ottawa Hospital Research Institute

University of Ottawa

Canada

Blair K. Gage (PhD) is a Scientist at the Ottawa Hospital Research Institute in the Regenerative Medicine Program and an Assistant Professor in the Department of Cellular and Molecular Medicine at the University of Ottawa. After a BSc in Biotechnology from UBC and BCIT, he completed a PhD in Cell and Developmental Biology exploring how transcription factors regulated pancreatic endocrine subtype specification from human pluripotent stem cells. His postdoctoral work shifted to generate organ-specific endothelial cells of the liver from human pluripotent stem cells to create potential cell-based and cell-informed therapeutics for liver disease and Hemophilia A. Dr. Gage started his lab in December 2023 and focuses on understanding how endothelial cells gain and maintain organ specific functions to build new therapies for human liver diseases where these functions are lost. The Gage lab’s primary research model is human pluripotent stem cells which are differentiated to become endothelial cells that can be transplanted in mice where they durably engraft and become functional. This research model and approach has potential therapeutic value as delivery of stem cell-derived endothelial cells to mouse models of Hemophilia A resulted in correction of the severe bleeding disorder by sustained production of bioactive coagulation factors. Building on this cell-based therapy leverages many computational, genetic, and molecular approaches to identify and apply new therapies aimed at controlling endothelial function to fight disease.

Prof. Edward Tuddenham


Emeritus Professor of Haemophilia

University College London

United Kingdom

Professor Edward (Ted) Tuddenham's journey into haemophilia began in 1969 at the Royal Victoria Infirmary in Liverpool, where he treated haemophilic patients. His interest deepened in Cardiff under Arthur Bloom, where he investigated the relationship between Von Willebrand Disease and Haemophilia A. Tuddenham dedicated seven years to purifying factor VIII, first at the University of Connecticut and then at the Royal Free Hospital Haemophilia Centre. His work led to the complete purification of factor VIII, enabling its amino acid sequencing and the cloning of its gene. These breakthroughs facilitated accurate carrier testing, antenatal diagnosis, and the discovery of mutations causing haemophilia A.

In 1987, Tuddenham established the Haemostasis Research Group for the Medical Research Council, focusing on rare bleeding disorders. In 2006, he returned to the Royal Free Hospital to pursue gene therapy for haemophilia. His team demonstrated the safety and efficacy of gene therapy for haemophilia B, using a vector that allowed high levels of factor IX expression. This resulted in most patients discontinuing replacement therapy and remaining free of spontaneous bleeding for up to 13 years. This vector was later modified by Uniqure, leading to the marketing approval of Hemgenix in 2023.

Collaborating with Amit Nathwani's laboratory, Tuddenham also helped develop a vector for transferring the factor VIII gene to treat Haemophilia A, culminating in market approval in the EU in 2022. He continues his work on gene therapy trials for haemophilia and other rare bleeding disorders, with 350 publications, an H-index of 74, and over 21,000 citations.


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