Scientists Use the Tweaked Genes of a Virus to Halt Vision Loss


What if you could tweak the genes of a virus to turn its ability to invade cells into a delivery system for eyesight therapy? That’s what researchers at Johns Hopkins School of Medicine say they’ve done by modifying an adenovirus, a type of virus that can infect tissue linings. The cutting edge gene therapy was developed to help those who suffer vision loss from a particular eye disorder—wet age-related macular degeneration (AMD).

Approximately 1.6 million Americans have AMD, the number one cause of vision loss. The disease is characterized by the growth of abnormal blood vessels that leak retinal fluid into the eye and destroy the macula, an area near the retina important for high acuity vision. This gene therapy both reduces fluid buildup and improves vision loss in humans, according to study results published in The Lancet.

The best current treatment for the disease requires injections of antibodies into the retina to suppress vascular endothelial growth factor (VEGF), a protein that is responsible for the growth of blood vessels—which in turn cause leaking fluid. But the problem is that patients must obtain these injections at four- to six-week intervals, or else the disease symptoms return and worsen over time. Peter Campochiaro, a professor of ophthalmology and neuroscience at Johns Hopkins Medicine's Wilmer Eye Institute and one of the authors of the study, explains that during this treatment, if a patient takes too long to get their next injection, the abnormal blood vessel net grows larger and recruits other cells. “That scarring causes permanent decrease in vision,” he tells Mental Floss. So over time, it’s common even for patients in treatment to “end up with less vision.”

His team has been working to make a form of injections that last longer, so patients don’t have to come in as frequently. For phase one of this trial, Campochiaro’s team recruited 19 participants to participate in a 52-week study. He was looking for people “who don’t have great visual potential, but have evidence of the disease process that you can measure in effect,” he says.

Since viruses are naturally good at getting into cells and depositing their genetic material, the researchers decided to modify a virus to deposit a gene that codes for a protein called sFLT01. sFLT01 blocks the factor that causes the abnormal vessels and fluid production. When the modified virus is injected into the eye, “the viral vector enters cells and deposits the gene, and the gene begins to produce the [sFLT01] protein,” he says. The protein binds to VEGF, preventing it from causing vessel growth and subsequent fluid leakage.

The 19 participants were divided into five different groups and given increasing doses of the viral vector. After determining there was no toxicity at the dose-limit of the first three groups, they proceeded to increase the dosage to its highest level.

Of the 11 participants with symptoms judged to be reversible, six showed “a substantial reduction in the fluid,” and four of those six saw “a pretty dramatic effect.” Those patients had big pockets of fluid in their retinas decrease, Campochiaro says. Better yet, the treatment lasted throughout the yearlong study, though the protein numbers peaked at 26 weeks, and then declined slightly (although not enough to reactivate disease symptoms).

In assessing why five patients saw no reduction in fluid, the scientists discovered those patients had pre-existing antibodies to the virus. They theorize that in these patients, the immune system may have killed the viral vector before it could deposit the genes, though they will have to do more research to prove this. This could be a problem in using this particular virus—a carrier virus called AAV2—since some 60 percent of patients tend to have these antibodies.

A possible solution might be to give resistant patients a surgical injection instead. During this procedure, scientists could take out the vitreous—a gel-like substance that gives your eye its round shape—and inject the vector surgically under the retina instead. While patients might prefer not to have surgery, “our data suggests that it doesn’t matter if there’s pre-existing antibodies [with this method],” he says.

Alternately, other viral vectors have proven to be more effective than AAV2, including a variation on the virus, AAV8, which provides better infections of the virus into the cell. Even more promising, the researchers recently finished a four-year study on a lentiviral vector (a totally different group of viruses) “that take [the genes] into the nucleus of the cell and inserts the gene right into the chromosomes,” Campochiaro explains.

His next steps will be to retest the treatment with a longer study period to identify just how long-lasting the effects are, as well as to test higher doses of the viral vector.

But right now, he is just excited that the gene therapy works. “We injected this gene, the gene is producing a protein, and you can measure that protein in the eye over time,” he says.

Is There An International Standard Governing Scientific Naming Conventions?


Jelle Zijlstra:

There are lots of different systems of scientific names with different conventions or rules governing them: chemicals, genes, stars, archeological cultures, and so on. But the one I'm familiar with is the naming system for animals.

The modern naming system for animals derives from the works of the 18th-century Swedish naturalist Carl von Linné (Latinized to Carolus Linnaeus). Linnaeus introduced the system of binominal nomenclature, where animals have names composed of two parts, like Homo sapiens. Linnaeus wrote in Latin and most his names were of Latin origin, although a few were derived from Greek, like Rhinoceros for rhinos, or from other languages, like Sus babyrussa for the babirusa (from Malay).

Other people also started using Linnaeus's system, and a system of rules was developed and eventually codified into what is now called the International Code of Zoological Nomenclature (ICZN). In this case, therefore, there is indeed an international standard governing naming conventions. However, it does not put very strict requirements on the derivation of names: they are merely required to be in the Latin alphabet.

In practice a lot of well-known scientific names are derived from Greek. This is especially true for genus names: Tyrannosaurus, Macropus (kangaroos), Drosophila (fruit flies), Caenorhabditis (nematode worms), Peromyscus (deermice), and so on. Species names are more likely to be derived from Latin (e.g., T. rex, C. elegans, P. maniculatus, but Drosophila melanogaster is Greek again).

One interesting pattern I've noticed in mammals is that even when Linnaeus named the first genus in a group by a Latin name, usually most later names for related genera use Greek roots instead. For example, Linnaeus gave the name Mus to mice, and that is still the genus name for the house mouse, but most related genera use compounds of the Greek-derived root -mys (from μῦς), which also means "mouse." Similarly, bats for Linnaeus were Vespertilio, but there are many more compounds of the Greek root -nycteris (νυκτερίς); pigs are Sus, but compounds usually use Greek -choerus (χοῖρος) or -hys/-hyus (ὗς); weasels are Mustela but compounds usually use -gale or -galea (γαλέη); horses are Equus but compounds use -hippus (ἵππος).

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An Ice Age Wolf Head Was Found Perfectly Preserved in Siberian Permafrost


Don’t lose your head in Siberia, or it may be found preserved thousands of years later.

A group of mammoth tusk hunters in eastern Siberia recently found an Ice Age wolf’s head—minus its body—in the region’s permafrost. Almost perfectly preserved thanks to tens of thousands of years in ice, researchers dated the specimen to the Pleistocene Epoch—a period between 1.8 million and 11,700 years ago characterized by the Ice Age. The head measures just under 16 inches long, The Siberian Times reports, which is roughly the same size as a modern gray wolf’s.

Believed to be between 2 to 4 years old around the time of its death, the wolf was found with its fur, teeth, and soft tissue still intact. Scientists said the region’s permafrost, a layer of ground that remains permanently frozen, preserved the head like a steak in a freezer. Researchers have scanned the head with a CT scanner to reveal more of its anatomy for further study.

Tori Herridge, an evolutionary biologist at London’s Natural History Museum, witnessed the head’s discovery in August 2018. She performed carbon dating on the tissue and tweeted that it was about 32,000 years old.

The announcement of the discovery was made in early June to coincide with the opening of a new museum exhibit, "The Mammoth," at Tokyo’s Miraikan National Museum of Emerging Science and Innovation. The exhibit features more than 40 Pleistocene specimens—including a frozen horse and a mammoth's trunk—all in mint condition, thanks to the permafrost’s effects. (It's unclear if the wolf's head is included in the show.)

While it’s great to have a zoo’s worth of prehistoric beasts on display, scientists said the number of animals emerging from permafrost is increasing for all the wrong reasons. Albert Protopopov, director of the Academy of Sciences of the Republic of Sakha, told CNN that the warming climate is slowly but surely thawing the permafrost. The higher the temperature, the likelier that more prehistoric specimens will be found.

And with average temperatures rising around the world, we may find more long-extinct creatures rising from the ice.