Ricki Lewis

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.

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 Many papers are preprints (not yet peer-reviewed) or embargoed, meaning we agree to not report findings until a certain date and time.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.

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.

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.

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.

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.

Early in this unforgettable year, a wet market in Wuhan, China, emerged as a possible step along the way, if not the place of origin, of the outbreak that would seed the pandemic of COVID-19. Prescient researchers have reached back to meat samples collected in 2013 and 2014 and used genetic testing to trace what might have happened again more recently: the magnification of viral infection from wild or farmed meat to large markets to restaurants. The report appears in PLoS ONE.

 

"This study shows the wildlife supply chain generates a one-two punch when it comes to spillover risk. It is known to increase contact rates between wildlife and people and here we show how it greatly amplifies the number of infected animals along the way," write Amanda E. Fine from the Wildlife Conservation Society, Viet Nam Country Program in Ha Noi and the Wildlife Conservation Society, Health Program, Bronx, New York, and colleagues.

 

COVID-19 was not a surprise to anyone familiar with the ways of viruses. A lot of folks weren't paying attention, even when repeatedly warned.

Collecting Rats

 

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

Graft-versus-host disease (GVHD) is counterintuitive

 

In the weeks and months following a transplant, a major concern is the recipient's immune system rejecting the "foreign" biological material. But in GVHD, the opposite happens: transplanted tissue unleashes a horde of T cells that spark a cascade of inflammation, within 100 days. Typically, GVHD follows a bone marrow transplant (BMT).

 

Eighty Percent Mortality
BMT has been used for more than half a century to treat and possibly cure certain cancers and single-gene conditions like sickle cell disease, immune deficiencies, and lysosomal storage diseases. BMT and hematopoietic stem cell (HSC) transplantation also enable a cancer patient to withstand higher doses of chemotherapy or radiation.

 

Acute GVHD develops in about half of the 30,000 or so patients who receive a BMT from a donor worldwide each year.  In children the complication can be particularly fierce. A blistery rash can become so extreme that the skin peels away, as can the intestinal lining, causing abdominal pain, diarrhea, and nausea and vomiting. Hepatitis may develop.

 

Only 20% of children who have steroid-resistant acute GVHD survive. But a treatment of mesenchymal stromal/stem cells (MSCs), called remestemcel-L (RYONCIL™), from Mesoblast Limited, is boosting survival to the 65-75% range among severely affected children, according to recent clinical trial findings.

 

On August 13, FDA's Oncologic Drugs Advisory Committee, an independent panel of experts who take a first peek at phase III clinical trial results, voted overwhelmingly to advise the agency to continue along the path to approval for RYONCIL. FDA's final meeting is slated for September 30.

 

To continue reading, please go to The Niche, where this post first appeared.  (Photo credit: Rose Spear on Flickr.)

 

In COVID-19, the sense of smell can diminish, vanish, or oddly skew, for weeks or months. The loss usually starts suddenly and is more than the temporarily dulled chemical senses of a stuffy nose from the common cold. As researchers followed up mounting reports of loss of olfaction, a surprising source of perhaps the longest-lasting cases emerged: stem cells in the olfactory epithelium.

 

A Common Symptom

 

Facebook groups may be ahead of the medical literature in providing vivid descriptions of the loss of olfaction as people swap advice and compare how long they've been unable to smell. The experiences can be bizarre, but at the same time, shared.

 

A favorite robust wine suddenly has no taste.

 

A parent must peek into or feel a child's diaper to see if action is needed.

 

Shower gel reeks, while clean dryer sheets, vinegar, detergent, and bleach have no odor.

 

Carbonated beverages release an odd, unnamable aroma.

 

Celebrations suffer as people can't smell birthday cake, pizza, even the stinky hallmark of Passover, gefilte fish.

 

Many people smell cigarette smoke, although none is around, or dirt, or the stench of rotten coffee grounds or moldy garlic.

 

Chefs can't smell their food. Runners can't smell their sweat. People fear they won't detect their house on fire.

Some people list the things they can smell, because these are far fewer than the odors that they can't detect.

 

Medicine has names for the disorders of olfaction. Anosmia is absence of the sense of smell, cacosmia the odor of rot, and phantosmia an "olfactory hallucination."

 

 

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

It isn't often that an investigation of a single patient who has a devastating, unrecognized disease leads to finding an existing drug that works, but also reveals something entirely new about gene function. A study from Dusan Bogunovic, PhD, Director of the Center for Inborn Errors of Immunity at the Icahn School of Medicine at Mount Sinai and colleagues just published in the journal Immunity, tells such a tale.

 

The young woman was only 18 when the investigation began. Her death from COVID-19 tragically juxtaposes the challenges of treating an ultrarare genetic disease with those of a pandemic infectious disease.

 

"We were so so sad when she passed. She was doing so well for the first time in her life for full 2 years. She was very happy, and her family was very happy to see her that way," said Dr. Bogunovic.

 

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