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Genetic Linkage

Final weeks to approval: NIH’s Anthony Fauci and FDA’s Peter Marks on what’s ahead before we can expect a safe COVID vaccine

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.

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A Drug Trio for COVID-19: Precedents in Cystic Fibrosis, HIV/AIDS, and Hepatitis C

(University of Washington Medicine)

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. 

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Long-Awaited Drug for Alkaptonuria (AKU), the First “Inborn Error,” On the Way to Approval in Europe

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.

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‘Challenge studies’: Should we be testing COVID vaccines by intentionally infecting volunteers?

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.

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Can Gene-Edited Stem Cells Treat Cystic Fibrosis?

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.

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5 COVID-19 Updates: Cats, Kids, Seniors, Blood, and an Old Vaccine

Times have been strange for us all, weird indeed for science journalists.

 

The initial manageable flow of news alerts to the media back in January quickly became an unceasing torrent. Every day now I receive dozens of news releases and heads-ups from science and medical journals. Many papers are preprints (not yet peer-reviewed) or embargoed, meaning we agree to not report findings until a certain date and time.

 

This is COVID article #42 for me. Today's post covers 5 news releases that seemed intriguing. Cats first!

 

Cats Get COVID From Owners

 

When four-year-old Negrito's human died of COVID-19, relatives took in the bereft European/Persian mix, who lived in Barcelona. Then Negrito developed difficulty breathing, so the new owners, who also had COVID, took him to the vet. Negrito's shortness of breath was due to an enlarged heart from a pre-existing condition, and he humanely crossed the rainbow bridge. But his bloodwork revealed a low viral load of SARS-CoV-2, although the cat had no other symptoms of COVID-19.

 

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

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A Cloned Przewalski’s Horse Evokes Memories of the Catskill Game Farm

On August 6, the first cloned Przewalski's horse was born in Texas. Kurt began with a cell nucleus from another of his kind frozen 40 years ago at the San Diego Zoo, and a surrogate run-of-the-mill domestic horse mother.

The cloning is a project of San Diego Zoo Global, Revive & Restore, and Viagen Equine.

 

"This new Przewalski's colt was born fully healthy and reproductively normal. He is head butting and kicking, when his space is challenged, and he is demanding milk from his surrogate mother," said Shawn Walker, chief science officer at ViaGen.

 

I was excited at this news, because these last surviving wild horses had made quite a lasting impression on me when I was very young.

 

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

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How the Various COVID Vaccines Work

COVID vaccine hesitancy is on the rise, perhaps in the wake of pressure to speed approval beyond scientific reason. But I think some of the hesitancy might be due to confusion over how so many different vaccines can target the same pathogen – and why this is a good idea.

 

The ultimate voice of scientific reason, Anthony Fauci said in a media webinar:

 

"I'm cautiously optimistic that with the multiple candidates with different platforms that we're going to have a vaccine with a degree of efficacy that would make it deployable. The overwhelming majority of people make an immune response that clears the virus and recover. If the body can mount an immune response and clear the virus in natural infection, that's a pretty good proof-of-concept that you'll have an immune response against a vaccine."

 

Having choices would provide options for people not covered by some of the vaccines, like those over age 65 and people with certain medical conditions. "It's a misperception that vaccine development is a race to be a winner. I hope more than one is successful, with equitable distribution," Fauci said.

 

The vaccines work in what can seem to be mysterious ways, but all present a pathogen in some form, or its parts, to alert the immune system to mount a response. Understanding how it all happens isn't like learning "how the sausage gets made." Knowledge may quell fears.

 

To continue reading, go to my blog DNA Science.

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Extinction of the Woolly Rhino: Ancient Genomes Point to Climate Change, not Overhunting

Two views of the forces behind extinction of the woolly rhino elegantly illustrate how scientific thinking shifts to embrace new knowledge – a phenomenon that reverberates as new findings about COVID-19 pour in.

 

Several large animal species ("megafauna") vanished with the last ice age, including woolly rhinos and mammoths, huge armadillos, cave lions, and sabertooth tigers. The prevailing view of the extinctions blamed overhunting by humans, a scenario that once roughly fit broad timelines. But in a new report in Current Biology, DNA data from preserved rhinos open a window into the past onto climate change. The new view charts the ebb and flow of long-ago rhino populations, while identifying specific gene variants that flesh out how well the animals had been adapted to the cold – putting them at a disadvantage when the climate warmed.

 

It's interesting to contrast how different types of data support different conclusions.

 

To continue reading, go to my DNA Science blog.

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Progress and a Setback in Treating Rare Genetic Diseases: Hemophilia A, CLN1, SMA, and DMD

In these strange days of the pandemic, it's easy to forget that people are still sick with the illnesses that we've always faced – and not just the common ones like cardiovascular disease and cancer. Times are particularly tough for the millions of people who have rare diseases.

 

Research continues into developing new treatments for rare diseases, despite the current difficulties, with some recent good news. But first, a setback.

 

Hemophilia A: Two More Years of Data Needed

 

On August 18, FDA ruled that a submission for approval of a gene therapy to treat severe hemophilia needs another two years of evidence to demonstrate that the treatment is really a "one-and-done." The agency is seeking data demonstrating "a durable effect using Annualized Bleeding Rate," a metric that the developer, Biomarin, claims had not been brought up prior to submission of the phase 3 findings.

 

Perhaps the extra scrutiny reflects the fact that treatment has been available since 1992 –recombinant clotting factor VIII. And gene therapy has been in the works for awhile. In fact, I interviewed the very first patient to receive gene therapy for hemophilia A, back in 1999. That trial used the same dangerous vector, a retrovirus, to deliver the gene that would kill Jesse Gelsinger later that year and derail the entire field.

 

 

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

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