Neda Razavi has enjoyed a successful track record across the biotech, pharmaceutical, and diagnostic industries. She develops marketing and commercialization strategy for products around the world with Roche Diagnostics as the lead of product marketing for a portfolio of automated sequencing library prep. With a bachelor of science in microbiology and cellular biology as well as a certificate in genomics and genetics from Stanford University, Neda Razavi maintains a passionate interest in genomics and genetics sciences, especially for clinical applications such as women’s health, human genomics, inherited genetic diseases and oncology.
Since its introduction in the 1990s, the prospects of gene therapy in clinical practice created great excitement and publicity. There have been many learnings along the way as early clinical trials represented gene transfer into patients with possible short-term effects but not permanently affecting the disease. A critical re-evaluation of approaches such as the development of new vectors for more targeted treatments has been crucial for the update of gene therapy. Gene therapy –the addition of the gene to restore a loss of function of two alleles mutation– is most effective in recessively inherited single-gene disorders. However, most gene therapy protocols are focused on multifactorial diseases such as malignancies where the therapeutic approach is quite different.
The fight against inherited single-gene diseases starts at the population level by carrier screening and prenatal testing, where parents undergo screening for specific genes that causes genetic diseases. The parents will have the option to terminate the pregnancy if the disease identified early in the cycle.
One innovator, Bluebird bio, has developed Zynteglo as gene therapy for Beta-thalassemia (beta-thal), a rare, inherited condition. The genetic disease involves functional adult beta-globin (HBB) production that is absent or significantly reduced. HBB is an essential component of hemoglobin, an oxygen-carrying protein found in the blood. A primary role of hemoglobin is to transport oxygen to various tissues from the lungs and, in turn, bring carbon dioxide from the tissues back into the lungs.
When beta-thal is present, mutations in the HBB gene occur that impact healthy red blood cells’ development and survival. Until very recently, allogeneic hematopoietic stem cell transplantation was the only permanent curative option available for patients suffering from transfusion-dependent beta-thalassemia. Transfusion-dependent beta-thal is a severe form that involves severe anemia and requires lifelong blood transfusions for HBB-level maintenance. Unfortunately, the transfusions carry a risk of unavoidable iron overload and progressive multi-organ damage. Bluebird bio is seeking to “recode the building blocks” with a more efficient and less invasive gene therapy approach that holds the promise of significantly improving the lives of patients with severe beta-thal.
Hemophilia A and B are other coagulation conditions that are great candidates for gene therapy. Per Hemophilia News Today, gene therapy for hemophilia involves using a modified virus (which does not cause disease) to introduce a copy of the gene that encodes for the clotting factor that’s missing in patients. Following treatment with the virus, patients should begin producing their own clotting factor normally.
The most innovative new technology enabling gene therapy is the invention of CRISPR/Cas9 that could allow a patient’s body to produce its own blood clotting factor. It uses a piece of genetic material and an enzyme that acts like molecular scissors to repair the genetic fault that causes clotting factor deficiency.
UniQure, Freeline, Sparks Therapeutics in partnership with Pfizer, Sangamo Therapeutics, and Biomarine are among the innovative companies developing gene therapy treatment for hemophilia A and B patients. Their clinical trials recruited a range of 10-30 patients each and the entire community is anxiously awaiting the results of this revolutionary treatment.
Neda Razavi 