Hello! This edition of Medical-Science Moments begins with…killer nanobots! That’s followed by:
FDA’s recent crackdown on dietary supplements
J&J leadership on drug pricing disclosure
Gene therapy news
Checkpoint inhibitor trial in prostate cancer
Human microbiome research
New cholesterol treatment guidelines
“D-flating” the hype on vitamin D
Please enjoy and, as always, I welcome any feedback or suggestions of items to consider for the next issue! – Dr. Dave
Invasion of Ingestible Digestible Nanobots!
In a proof-of-concept study, scientist recently developed a new type of orally administered vaccine delivery vehicle with a tiny motor and showed it can drive itself to the intestinal mucosa in mice and inject a vaccine, potentially protecting against infections. Mucous membranes – found in the nose, lungs, GI tract and other tissues – are a first line of defense against pathogens, yet current vaccines stimulate antibodies in the bloodstream. If vaccines could rouse a response in mucous membranes, the antibodies may be able to stop an infection earlier, before it gets to the bloodstream. The scientists showed that mice given the pea-sized, vaccine-carrying vehicles had greater immune response than those given the vehicles without the vaccine. The vehicle eventually disintegrate in the GI tract, leaving no toxic materials behind. The researchers are now testing the system in animal models to see if it actually prevents disease.
Development of “digestible injectables” is gaining momentum. For example, a report in Science described a tortoise-shaped, pill-sized vehicle that travels and sticks to the stomach lining, where it delivers insulin via a tiny pin prick. The approach, demonstrated in rats and pigs, holds potential promise for oral delivery of macromolecules that otherwise would be unabsorbed or destroyed in the GI tract. And a Swiss team reported developing tiny robots that can change shape and swim through the bloodstream to deliver drug to specific locations in the body.
Gottlieb Grabs Dietary Supplement “Bad Actors”
FDA commissioner Scott Gottlieb, MD, recently issued a statement about new measures the agency will take related to dietary supplements – now taken by about two-thirds of Americans (as well as by Dr. Gottlieb).He said that one of his top goals is achieving “the right balance between preserving consumers’ access to lawful supplements, while still upholding our solemn obligation to protect the public from unsafe and unlawful products, and holding accountable those actors who are unable or unwilling to comply with the requirements of the law.” As an example, he noted that on that same day, the agency sent 12 warning letters and 5 advisory letters to companies illegally selling 58 products, many claiming to be Alzheimer’s cures. The list of offending companies is here. The Council for Responsible Nutrition, which represents supplement manufacturers, said they support rooting out “bad actors” (but last time I checked, Justin Bieber and Miley Cyrus were still around).
J&J Leads the Way
On February 7, Johnson & Johnson announced it will start disclosing list prices of its prescription drugs in television ads, making it the first pharma company to take this step. The decision comes amid growing scrutiny of high drug prices, and follows a Trump administration proposal to require drug list prices in TV ads. U.S.H.H.S. Secretary Alex Azar praised the move, saying, “We commend Johnson & Johnson for recognizing the value of informing consumers about list prices and for doing so voluntarily. We call on other manufacturers to follow their lead.” The company will include both the list price of a product (before any rebates or discounts to insurers or pharmacy benefit managers) as well as potential out-of-pocket costs that patients will pay. Ads for the company’s blood thinner medication Xarelto® will be the first to include price information.
Gene Therapy Stays in the Spotlight
This is just a sampling of recent findings and events related to this very active and exciting frontier:
- Recently scientists presented interim results of the first patients to receive in vivo genome editing. The researchers showed that SB-913 and SB-318, in vivo zinc finger nuclease gene-editing candidates for Hunter Syndrome and Hurler’s Syndrome, respectively, successfully made corrective edits to the DNA of the patients and appeared to be safe. The study sponsor, Sangamo Therapeutics, plans to move ahead and determine if the successful gene editing translates to clinical benefits.
- The company UniQure announced updated Phase 2b data on its investigative hemophilia B gene therapy, AMT-061. AMT-061 uses a viral vector to deliver a mutated gene that revs up production of Factor IX (FIX), the clotting factor that’s compromised in hemophilia B. The updated data suggest the activity of FIX from AMT-061 is sustainable out to at least 12 weeks.
Then there’s the CRISPR gene-editing technology itself – like Helen of Troy, the object of a major battle, but instead of Sparta and Troy it’s between the University of California Berkeley and the Broad Institute and their collaborators, MIT and Harvard. And potentially with billions of dollars at stake. UCB argued that a patient previously given to BI overlapped theirs. On February 8, the US Patent and Trademark Office ruled in favor of UCB, though BI stated that the new decision does not affect their CRISPR patent.
Keytruda Promising in Prostate Cancer
Merck’s checkpoint inhibitor Keytruda® has generated impressive results in melanoma, non-small-cell lung cancer, and a number of other solid- and non-solid tumor indications. Recently Merck announced it is launching three Phase 3 trials of Keytruda as combination treatment for prostate cancer after the drug showed anti-tumor activity in a Phase 1b/2 trial.
Happiness from…Gut Bugs?
The study of the gut microbiome and health has been a highly active and sometimes controversial area of research. Recently, and for the first time, a large scale human population study has linked depletion of certain bacteria in the gut (Coprocuccus and Dialister) to depression. The study in more than 2,100 people also found that some gut bacteria species may produce or breakdown molecules that act on the human nervous system. Yogurt anyone?
In vitro, in vivo and in…WHAT?
Speaking of the gut microbiome, many studies of it involve analyses of…well, excrement. Indeed, feces can flag important information, from DNA to immune function to activities of enzymes. So perhaps it’s not surprising that researchers recently proposed, in the journal Gastroenterology, a name for the field of excrement experimentation: in fimo. In the article, the scientists make the case for the Latin-derived term (from fimus) over others, including “fecal,” because its Latin root doesn’t relate to excrement; and the English term “feces,” because it originally referred to dregs in a container of wine.
Cholesterol Guidelines Updated
The American Heart Association, American College of Cardiology and other organizations have issued the first update since 2013 of the blood cholesterol treatment guidelines (announced in November 2018, but full article is still in press). The biggest change: whereas the 2013 guidelines only recommended statin therapy to reduce LDLs, the update adds PCSK9 inhibitors and ezetimibe for secondary prevention, if LDL reduction is insufficient with statins alone.
Vitamin D Minus?
As noted in Science News, Vitamin D is like a Kardashian: Its notoriety came from nowhere about 10 years ago, and has been the buzz of the nutrition and medical community ever since. Besides strengthening bones, the fat-soluble vitamin initially appeared to protect against such varied maladies as heart disease, cancer, multiple sclerosis, asthma and depression. But more recent and scrutinizing research appears to be “D-flating” at least some of the benefits of this nonetheless essential nutrient. For example:
While most elderly are generally thought to have suboptimal status of vitamin D, putting them at risk for weaker bones and fractures, a recent study in adults > 70 years old showed no significant changes in bone mineral density with vitamin D supplementation.
A recently reported intervention study in nearly 26,000 Americans followed for more than five years showed no evidence of protection against cardiovascular disease or cancer.
…But the research isn’t all negative. For example, growing evidence suggests a protective effect against multiple sclerosis. And Harvard’s Walter Willet, MD DrPH, a co-author on a number of the recent negative studies, suggests 1000-2000 IU vitamin D per day is still “a reasonable thing to do.”