Science Policy For All

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Science Policy Around the Web – September 5, 2017

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By: Sarah L. Hawes, PhD

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Image: By Simon Caulton [CC BY-SA 3.0], via Wikimedia Commons

Gene therapy

FDA approves breakthrough gene therapy for childhood leukemia

Last week, the FDA approved use of gene therapy for the first time, to be used against resistant or relapsed acute lymphoblastic leukemia (ALL) originating in B-cells. The treatment, called Kymriah, was made by Novartis Pharmaceuticals in collaboration with University of Pennsylvania. It is a form of CAR T-cell therapy, in which a patient’s own immune cells are extracted and genetically modified to better identify and attack cancer-laden B-cells before being infused back into the patient.

Because the cellular feature which modified T-cells use to seek and destroy cancerous cells is also present on healthy B-cells, treatment carries risks including hypoxia, hypotension, and suppressed immune function. A life-threatening immunological reaction called cytokine release syndrome appears more commonly in adults, and may explain patient age-restriction (25 and under) on FDA’s approval.

For patients with otherwise intractable cancer, Kymriah may be a literal life-saver. In a recent clinical trial on 63 patients with drug-resistant or recurring ALL, Kymriah lead to remission in 83% of cases three months post-treatment.

While announcing approval of Kymriah, FDA Commissioner Scott Gottlieb asserted that the FDA is “committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.” This has been substantiated for Kymriah in particular using both Priority Review and Breakthrough Therapy mechanisms. These speed FDA approval, thereby shortening pharmaceutical companies’ delay to profit, and have helped to drive activity in the promising CAR T-cell research arena in recent years.

Despite the success of these mechanisms in bringing a breakthrough cancer therapy to market faster, Novartis insists that a $475,000 price tag for one-time treatment is conservative considering the high cost of drug development and low number of candidate patients. This sobering figure is made worse by the fact that some cases indeed recur several months following Kymriah. Novartis is currently working with Medicare on a plan for outcome-based pricing, so that the pharmaceutical company is only paid if patients respond to the therapy.

(FDA News Release; Jessica Glenza, The Guardian)

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Image: By NOAA, via Wikimedia Commons

Emergency preparedness

Hurricane Harvey illustrates the importance of disaster preparedness for research institutions (again) 

The US National Academies of Sciences, Engineering, and Medicine released a report just last month highlighting weaknesses in disaster preparedness in biomedical research facilities, and issuing recommendations to enhance the resilience and continuity of research in the face of adversities including natural disasters, fires, and cyber threats. Costs of unpreparedness are high. In In 2012 Hurricane Sandy is estimated to have caused NYU more than $20 million in research equipment, and killed thousands of mice housed in New York laboratories, including many transgenic strains which took decades to develop and existed nowhere else on earth.

Hurricane Harvey’s toll on the scientific community is similarly, incalculably high. University of Houston’s infant rhesus monkeys ran out of formula and had to be weaned early. Loss of refrigeration capability jeopardized precious tissue and reagents, not to mention rendering some agents hazardously unstable. The University of Texas at Austin Marine Science Institute lost the roof off a microbial-ecology lab, forcing trainees to abandon their work and move to alternative institutions.

Some fared better due to advanced planning. For instance, Baylor College of Medicine was protected from Harvey by a wall installed around their campus after 2001 Tropical Storm Allison cost them 60,000 breast-cancer samples and thousands of laboratory animals. To support less fortunate Texas researchers, the broader scientific community has used hashtag #SciHelpTX on Twitter to advertise sharable resources such as open lab space, computers, and animal colony husbandry.

Hopefully Harvey has driven home the message that preparedness is a necessary investment going forward. Enacting preparations remains up to individual institutions’ policies; a list of recommendations by the National Academies can be found here.

(Emma Marris, Nature News)

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Image: Wikimedia Commons

Gene therapy

Correction of a pathogenic mutation in human embryos? Maybe! The exploration continues

An August 2017 publication in Nature reports success using CRISPR-Cas9 to delete targeted sections of gene responsible for producing familial hypertrophic cardiomyopathy from human zygotes. The study, led by Dr. Shoukhrat Mitalipov, involved collaboration between the Salk Institute, Oregon Health and Science University (OHSU) and Korea’s Institute for Basic Science. By introducing a short-lived version of CRISPR, an enzyme, and a repair template into a healthy egg prior to fertilization but simultaneously with sperm bearing the targeted genetic defect, authors believe they ensured the gene excisions would take place early, and be carried throughout all following cell divisions. They believe this technique avoids unintended edits and mosaicism, in which both diseased and repaired cells exist side by side in the organism. The team found both the deleted genes and the template for replacement absent, and believe the genome repair used the healthy genes from the egg. They suggest this is due to certain evolutionary resiliencies associated with early stage eggs.

Other researchers responded by emphasizing the remaining uncertainties and importance of maintaining a focus on research as opposed to pushing too quickly toward application of germline editing techniques with the potential for producing heritable genetic changes. Complex ethical questions remain around germline editing even should techniques be perfected for any specific section of the genome. This research could not receive government funding due to the creation and destruction of human embryos.

Within three weeks, a preprint article questioned the likelihood of the egg serving as a template for repair of the genome’s deleted genes. The authors state that following fertilization the egg and sperm DNA are not in close enough contact for such borrowing, and propose two alternative scenarios: Either the egg failed to incorporate the sperm DNA which is sometimes seen with in vitro fertilization, or failed to replace the missing segment at all. Either would have resulted in an absence of the targeted paternal or template genes. Mitalipov has promised to respond point by point.

(Kelly Servick, Science Magazine)

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Written by sciencepolicyforall

September 5, 2017 at 5:29 pm

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