Gene therapy success!
For the first time, gene therapy has successfully treated a common genetic disorder: sickle cell disease (SCD), which affects 100,000 people in the United States and millions globally. People with SCD have abnormal hemoglobin due to a mutation in the gene for a subunit of that protein called beta-globin, causing red blood cells to stick together. As reported in NEJM, researchers harvested bone marrow stem cells from the SCD patient, a 13-year-old boy, and transferred into them a mutated gene that produces a form of beta-globin that interferes with the patient’s faulty beta-globin, preventing red blood cells from clumping together. The researchers then put the modified stem cells back into the boy’s bone marrow where, after about 3 months, they produced normal-behaving hemoglobin. Now at age 15, the boy does not need to take SCD medications.
MS treatment breakthrough
Earlier this week, the FDA approved a new medication, ocrelizumab (Ocrevus™, Roche/Genentech), for treating aggressive forms of MS, which affects more than 400,000 Americans and 2 million people worldwide. Unlike most other MS therapies which target T-cells, the new treatment targets B-cells, which research suggests play a bigger role in the disease than previously thought.
And FDA guidance about off-label promotion is (drumroll!)…
…off again, for at least a year. The agency changed the previous date for the much-anticipated rule from March 21, 2017, to March 19, 2018 to “respond to an industry petition objecting to how it put out the rule on intended uses of regulated products.” On the other hand, as reported in STAT+, Arizona has just become the first state in the nation to pass a law that allows promotion of medicines for off-label uses, provided the information given to physicians is truthful.
A fountain of youth…at least for mice
Scientists have created a drug that reverses some of the effects of aging, according to a study reported in Cell by researchers from Erasmus University in the Netherlands. Elderly mice given the drug showed reversal of kidney damage, increased exercise stamina and improved fur coat. The drug – a peptide that targets a protein called FOXO4 involved with cell aging and programmed cell death (apoptosis) – apparently selectively kills old cells involved with inflammation and aging. By clearing these senescent, defective cells, newer younger cells can proliferate, reversing some of the negative effects of aging. The drug did not affect younger cells.
Speaking of mice, other research reported in Nature Chemical Biology shows a newly created, orally administered drug can effectively reverse diabetes symptoms – not just treat them, as current drugs do. The drug inhibits an enzyme in the body called LMPTP, which interferes with insulin receptors on cells; by inhibiting LMPTP, mice with diabetes regained sensitivity to insulin, resulting in normalization of blood glucose levels. The drug didn’t appear to have any side effects – at least, according to the mice.
Take heart in these 10 foods!
An analysis published in JAMA showed that suboptimal intakes of 10 foods were associated with nearly half (45.4%) of all US cardiometabolic (CM) deaths (cardiovascular disease, stroke and type 2 diabetes). Using nationally-based food intake and disease data, investigators compared current and past intakes of various foods and nutrients with optimal intakes associated with the lowest risk for CM disease and death, and determined diet-disease associations through mathematical modeling. The findings? Most CM-deaths were related to high sodium, followed (in order) by low nuts/seeds and high processed meats; low seafood omega-3 fats, vegetables and fruits; high sugar-sweetened beverages; low whole grains; high unprocessed red meats; and low polyunsaturated fats.
We all know exercise is beneficial. Now, a new study in Cell Metabolism adds to the growing evidence supporting high-intensity interval training (HIIT) specifically. HIIT involves short bursts of “all out” high intensity activity interspersed with lower-intensity activity. The new study, from the Mayo Clinic, included people aged 18-30 years and 65-80 years old randomly assigned to 3 months of HIIT, weight training, or a combination of the two. Muscle biopsies showed that HIIT reversed many age-related differences in mitochondria (cells’ powerhouses), increasing their ability to generate energy: by 69% in the older participants vs. 49% in the younger ones (sorry, whippersnappers!). HIIT also reversed age-related physiological declines, improving lung, heart and circulatory function. Weight training increased muscle mass, but didn’t improve cardiorespiratory function.
Cancer-causing mutations? Copy that!
Usual wisdom chalks up cancer-causing mutations mostly to either inherited or environmental factors. But in a recent report in Science, Johns Hopkins researchers found two-thirds of such mutations actually result from a different source: DNA replication errors in stem cells. In various body tissues, stem cells divide to create new tissue cells. Using mathematical modeling, the investigators showed that tissues with more stem cells and stem cell divisions had more replication errors, which strongly correlated with tissue-specific cancer incidence. Given their findings and that DNA replication errors are random and (currently at least) unavoidable, the authors suggest that primary prevention works best in cancers driven more by mutations due to environmental causes (e.g., as with lung cancer and smoking) compared to those mostly driven by DNA replication errors (e.g., pancreatic cancer). The latter types of cancers can be best managed through early detection and treatment. Cancer experts’ reactions to the findings varied from skeptical to highly positive.