Testing the Efficacy of New Gene Therapies More Efficiently

Recently, a research team headed by Janine Reichenbach, a UZH professor and Co-Head of the Division of Immunology at the University Children's Hospital Zurich, has developed a new cellular model that enables to test the efficacy of new gene therapies much more efficiently. "We used Crispr/Cas9 technology to change a human cell line so that the blood cells show the genetic change typical of a specific form of Chronic Granulomatous Disease," explains the pediatrician and immunologist. In this way, the modified cells reflect the disease genetically and functionally. Until now, scientists had to rely on using patients' skin cells that they had reprogrammed into stem cells in the lab. This approach is laborious, and requires considerable time and money. "With our new testing system, this process is faster and cheaper, enabling us to develop new gene therapies for affected patients more efficiently," says Janine Reichenbach.
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AveXis SMA Gene Therapy Advances Toward Pivotal Trial

AveXis has posted top-line data from a phase 1 trial of its gene therapy against spinal muscular atrophy (SMA). All 15 patients were event-free at 13.6 months of age, a significant improvement over the natural history of the disease. The phase 1 gave three babies with the genetic muscle weakness disease a low dose of a gene therapy designed to provide them with a functioning SMN gene. A further 12 babies received the larger amount of the gene therapy AveXis sees as the proposed therapeutic dose. By the age of 13.6 months, none of the subjects had suffered an “event”, defined by AveXis as death or the need for medically prescribed respiratory assistance for 16 hours a day for two weeks. With natural history data suggesting 25% of babies with SMA would experience such an event by 13.6 months of age, the results have encouraged AveXis to push ahead with plans to start a pivotal trial of AVXS-101
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Scientists Discover Metabolic Pathway that Drives Tumor Growth in Aggressive Cancers

Mount Sinai researchers have discovered that a rheumatoid arthritis drug can block a metabolic pathway that occurs in tumors with a common cancer-causing gene mutation, offering a new possible therapy for aggressive cancers with few therapeutic options, according to a study to be published in Cancer Discovery. Ramon Parsons, MD, PhD, Ward-Coleman Chair in Cancer Research and Chair of the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, led a team that studied how a mutation of the PTEN gene rewires a metabolic pathway in tumors, channeling increased amounts of the amino acid glutamine into the pathway, speeding up DNA production, and causing uncontrolled growth of the tumor. The team discovered that leflunomide, an oral rheumatoid arthritis drug approved by the U.S. Food and Drug Administration, blocks an enzyme in this pathway and damages the DNA created through the pathway, killing PTEN mutant cancer cells while leaving healthy cells untouched.
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Neuroscientists Pinpoint Key Gene Controlling Tumor Growth in Brain Cancers

Cedars-Sinai investigators have identified a stem cell-regulating gene that affects tumor growth in patients with brain cancer and can strongly influence survival rates of patients. The findings, published in the online edition of Scientific Reports, could move physicians closer to their goal of better predicting the prognosis of patients with brain tumors and developing more personalized treatments for them. To enhance understanding of how glioma cancer stem cells (GCSCs) reproduce and how they affect patient survival, investigators spent three years analyzing the genetic makeup of more than 4,000 brain tumors. During their investigation, they identified the gene, called ZEB1, that regulates tumor growth. The investigators' analysis suggests that brain cancer patients who don't have the gene tend to have lower survival rates.
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Gene Therapy Treats Sickle Cell Disease in Teenager Using Lentiviral Vector

Gene therapy that delivered an antisickling variant of hemoglobin in an autologous hematopoietic stem cell (HSC) transplant has ameliorated symptoms of severe sickle cell disease (SCD) in a 15-year-old boy, according to a report published in the March 2 issue of the New England Journal of Medicine. SCD results from a point mutation at amino acid position 6 in the beta globin gene that causes polymerization of the protein and sickling of the erythrocytes that contain it, under low-oxygen conditions, obstructing microcirculation and damaging organs. Hemoglobin A (HbA) is the normal subunit; HbS is the one altered by the sickle cell mutation
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Bluebird Bio Announces Publication of Case Study on First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine

Bluebird bio, Inc., a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, today announced the publication in the New England Journal of Medicine of a case study on Patient 1204, the first patient with severe sickle cell disease (SCD) to be treated with gene therapy. This patient, who was 13 years old at the time of treatment, was treated with LentiGlobin drug product in the HGB-205 clinical study conducted in Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. The data in the publication reflect 15 months of follow-up, and a brief summary of this patient’s outcomes with 21 months of follow-up was presented at the 58th American Society of Hematology Annual Meeting in December 2016.
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DNA May Offer Rapid Road to Zika Vaccine

Last August, scientists injected a potential vaccine for Zika virus into a human being — just 3½ months after they had decided exactly what molecular recipe to use. In the world of vaccine development, 3½ months from design to injection is “warp speed,” says vaccine researcher Nelson Michael of the Walter Reed Army Institute of Research in Silver Spring, Md. Clinical trials can take years and epidemics can burn out before vaccines make it to doctors’ shelves. Even vaccine creation is typically sluggish. But in this case, the vaccine is a bit of DNA, which means scientists can get moving fast. Unlike some traditional methods, DNA vaccines don’t use dead or weakened viruses. Instead, they rely on a snippet of genetic material. This “naked” DNA carries, for example, the blueprints for Zika proteins. It’s just a long sequence of DNA blocks.
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Glowing Mice Suggest New Gene Therapy Technique

A collaboration between chemists and gene therapy experts produced a new way of inserting the code for modified proteins into the cells of mice. If successful in humans, the technique could be useful for vaccines or cancer therapies. This research was made possible through coordination between the chemists and experts in imaging molecules in live animals, who rarely work together directly. With this partnership, the synthesis, characterization and testing of compounds could take as little as a week.
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Broad Institute Wins Big Battle Over CRISPR Gene-Editing Patent

The U.S. patent office has delivered a potentially lucrative victory to bioengineer Feng Zhang of the Broad Institute in Massachusetts, regarding patents for an extraordinarily useful gene-editing tool. CRISPR, a technology that's already worth billions of dollars, is shaping up to play a big role in medicine and medical research because it can edit DNA with unprecedented accuracy. But exactly who has the right to profit from the technology has been up for debate. Wednesday the U.S. Patent and Trademark Office said patents issued to the Broad Institute in 2014, and then challenged by the University of California, Berkeley, are in fact valid.
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RNA Vaccine for Zika Shows Promise

In the last year, a diverse suite of anti-Zika vaccines has rapidly advanced through preclinical development and into human trials. A Phase 1 trial testing one approach, which relies on DNA to encode vaccine components, has already yielded encouraging results. Now, another nucleic acid, messenger RNA (mRNA) is joining the Zika-vaccine toolbox. According to a study published in Nature today (February 2), a single shot of a vaccine containing Zika virus mRNA encapsulated in a lipid nanoparticle induced protective immune responses in both mice and Rhesus macaques. “It’s a novel vaccine platform. It has not been explored in great detail in humans yet, but it will have more clinical experience going forward,” said Dan Barouch, who directs the Center for Virology and Vaccine Research at Harvard Medical School and was not involved in the present study.
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