Ricki Lewis

As tens of thousands of people participate in phase 3 clinical trials on COVID-19 vaccine candidates, the focus is turning to the approval process: Will the approved vaccines be safe and effective? For how long? Has politics been injected into the process?

To reassure the public that the checks and balances that regulatory agencies have always had in place will prevail, Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases, and Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research, discussed the current state of the science with Howard Bauchner, MD, at JAMA Live Q+A webinars for the media on September 25 and October 5.

Their comments interweaved into a compelling narrative is like visiting with two scientific maestros.

To continue reading, go to Genetic Literacy Project, where this post first appeared.

Teaming treatments has long been a strategy to quell cancer, override mutations, and fight viruses. Will that be a winning strategy against SARS-CoV-2, the virus that causes COVID-19?

Surgery, chemo, and radiation are the traditional triple-punch against cancer, with more recent targeted therapies moving to the frontline. The same road has unfolded for cystic fibrosis (CF).

Fixing Errant Ion Channels

The first treatments for CF were simple: pounding on the chest to dislodge sticky mucus, sprinkling digestive enzymes on applesauce, and using old drugs to combat inflammation and infection.

The new CF drugs that have revolutionized treatment for most patients are small molecules that interact with the malformed ion channels that lie behind the disease. The channels are tiny tubes built of cells festooned with proteins that regulate the balance of water and salts in many body parts – hence the diverse symptoms of breathing difficulty, poor fat digestion, salty sweat, lung infections, and male infertility.

The new drugs work in three related ways.

To continue reading, go to my blog DNA Science, where this post first appeared. 

The European Medicines Agency has just recommended extending use of an existing drug, nitisinone (Orfadin), to treat alkaptonuria (AKU). AKU holds a special place in the history of genetics as the first "inborn error of metabolism" described. It affects one in 250,000 to one in a million people.

The route to impending approval took two decades, illustrating factors that make the quest to discover, develop, and deliver a treatment for a very rare disease so challenging. There's no "Operation Warp Speed" for the rare disease community. Sometimes there aren't even enough participants to carry out a clinical trial that is controlled, relying instead on comparisons to the natural history of a disease, or enrolling one patient at a time in an "N+1" study.

I last wrote about AKU in 2014, calling it "black pee disease." I'm happy to report now on the progress in Europe, but won't use that attention-grabbing descriptor, because it minimizes the severity.

A Peculiar Condition and an Astute Physician

To continue reading, go to my DNA Science blog at Public Library of Science.

To those who've never thought about volunteering to be intentionally infected to test a vaccine, the idea may at first seem a bit bonkers. But such "challenge" studies not only have a rich history, but nearly 40,000 people have already checked the box "I am interested in being exposed to the coronavirus to speed up vaccine development" at 1daysooner, a website and non-profit organization that launched in April.

Challenge studies go by other names: "controlled human infection models," "human viral challenge," and "purposeful infection." Dripping virus-tainted saltwater into a volunteer's nostrils enables researchers to track infection, and the immune system's response to it, right from the start. The approach complements phase 3 clinical "field" trials of efficacy that await natural infection in the community.

To continue reading, go to Genetic Literacy Project, where this post first appeared.

Drugs that restore the shape of the errant protein behind cystic fibrosis (CF) have, over the past eight years, helped the majority of patients, who have certain mutations. Gene-corrected stem cells might offer a "mutation agnostic" option to CF.

CF results from a glitch in a glycoprotein with the unwieldy name "cystic fibrosis transmembrane conductance regulator", or CFTR. The proteins normally fold into channels that regulate the flow of ions into and out of cells, controlling the balance of water and salts in linings and barriers of the respiratory tract, pancreas, intestines, and elsewhere. If the proteins can't fold correctly, or can't migrate to the cell's surface and then open and stay that way, the resulting ion imbalance allows too much water into lining cells and secretions thicken. CF symptoms ensue, such as difficulty breathing and digesting. The Cystic Fibrosis Foundation has a helpful video (see below) both on why CF develops and the promise of gene-editing.

The most common CF mutation, F508del, removes just one of the protein's 1,480 amino acids (a phenylalanine), and that's enough to wreck the ion channels. Ninety percent of patients have at least one F508del variant. Researchers have identified more than 2,000 variants in the CFTR gene, about 350 of which are pathogenic.

To continue reading go to The Niche, where this post first appeared.