London researchers have made a rare breakthrough in a rare disease: hemophilia A. In the small-scale clinical study, patients received injections of a missing gene that promotes the production of the factor VIII clotting protein absent in these patients. Results reported in NEJM showed that six of the 7 patients in the high-dose cohort maintained normal levels of factor VIII after a full year. Also amazing, those in the high-dose cohort had an average of 16 bleeding events per year prior to therapy and this was reduced to 1 event per year after therapy. These findings are particularly significant because prior gene therapy studies have shown effectiveness only in hemophilia B sufferers, not hemophilia A, where a different clotting protein is the culprit.
Good news, bad news. Companies that are developing cutting-edge gene therapy recently got some good news when the FDA approved the first gene therapy in the US and indicated they will expedite the approval of experimental gene therapies. Great. The bad news? Genes (specifically, modified genes) are in high demand. A recent NY Times article explains that “firms that can (manufacture the genes) are swamped with orders and requests.” Organizations are having to sign-up years in advance to secure manufacturing slots, often before proof-of-concept is complete. Risky. Expensive. Decisions have to be made and one company, Bluebird Bio, has taken the bull by the horns, securing their own manufacturing. We’ll keep you updated, and for an InsightCity approved view of men and skinny jeans go here.
[Editor’s note: two-thirds of InsightCity approved anyway.]
Last week, the FDA approved Novartis’ Kymriah—a “living drug” that works by making immune cells realize they should get rid of those pesky leukemia cells making a mess of things. We’ve been following this story since June, because it’s really cool for a couple reasons. First, it marks the first time a gene therapy has been approved for use in the US, although more CAR-T treatments are in the pipeline. Second, the treatment is designated for the most prevalent form of childhood cancer in the US—acute lymphoblastic leukemia (ALL). There is a bit of worry that the treatment is prohibitively expensive, which is what sunk the first gene therapy approved in the EU, but maybe competition will help drop prices.
Here’s a riddle for you. What has four wheels and costs $150K? Hint: it weighs 150 pounds. Give up? It’s the new portable device that automates CAR-T production—we had to Google it, too. The current gene therapy process isn’t what we’d call convenient. It involves: flying the patient or patient’s blood to one of only a dozen research centers globally, a room full of smart people, and dozens of hours just to process one person’s cells. As you can imagine that rings up a hefty price tag—some estimates are around $500K. With the new portable device, Prodigy, the goal is to automate this tedious procedure and take gene therapy to the patient instead of the other way around.
While still a long way from the finish line, gene therapy looks promising for blocking the onset of Alzheimer’s disease. Researchers at Imperial College London injected lentivirus, which contains the PGC-1-alpha gene, into the hippocampus and the cortex of mice susceptible to the development of Alzheimer’s disease. Compared to a control group of similarly susceptible mice, the treated group showed little development of amyloid plaques. Not to get too technical here but amyloid plaque is stuff believed to lead to bad things. Like strokes in golf, you want fewer of them. Treated mice also showed no loss of brain cells in the hippocampus and normal performance on memory tasks. All together now… Sci-ence!, Sci-ence!, Sci-ence! Well done, smart people.
Medication can be tricky. Two people swallowing the same pill can end up having wildly different outcomes (yay, genetic diversity). Antidepressants are especially notorious for their unpredictability, thanks to the complexity of depression’s underlying pathways. Northwestern University scientists have now discovered that using gene therapy to thwart one of these pathways results in significant reduction of depressive symptoms in mice. The researchers injected a nontoxic virus that expresses a gene meant to stop the production of proteins called HCN channels in the hippocampus. What did they find? No proteins = reduced depressive symptoms. This “straight-to-the-source” therapy has significant implications for the illness—both identifying its genetic underpinnings, and setting the stage for a treatment to help the millions of patients still in search of effective therapies.