The first-in-human clinical trial targeting Alzheimer's tau protein

So far, many of the antibody drugs proposed to treat Alzheimer's disease target only the amyloid plaques. Despite the latest clinical trial that is hailed as our best chance in the quest for treating AD, all later phase trials have failed with many causing severe side effects in the patients, such as abnormal accumulation of fluid and inflammation in the brain. One of the reasons for side effects, many speculate, is due to the antibody directing a reaction towards normal amyloid present in blood vessels or simply releasing beta-amyloid caught in the vessel wall.

The authors of the study have developed a vaccine that stimulates the production of an antibody that specifically targets pathological tau, discovering its "Achilles' heel." It is able to do this because healthy tau undergoes a series of changes to its structure forming a new region that the antibody attacks. This new region (the "Achilles' heel"), while not present in healthy tau, is present in diseased tau early on. Therefore, the antibody tackles all the different varieties of pathological tau. In addition to this important specificity, the antibody is coupled to a carrier molecule that generates a considerable immune response with the added benefit that it is not present in humans, thus avoiding the development of an immune reaction towards the body itself.

Side effects have included a local reaction at the site of injection. This skin reaction is thought to occur due to the aluminum hydroxide, an adjuvant used in vaccines to enhance the body's own antibody production. No other serious secondary effects were directly related to the vaccine. Overall, the safety of the drug and its ability to elicit an immune response were remarkable.

While many trials against Alzheimer's disease stubbornly continue to target amyloid, our study dares to attack the disease from another standpoint. This is the first active vaccination to harness the body's ability to produce antibodies against pathological tau. Even though this study is only a phase 1 trial, its success so far gives the authors confidence that it may be the answer they are looking for to halt the progress of this devastating disease.


Ant species ready to take over world, suggests new study

An ant species living in Ethiopian forests is displaying signs of taking over the whole world. It is already moving out of the forests into agricultural land and construction sites. And, supercolonies spanning as much as 38 kilometres have been found.

Scientists believe that this ant species, formally called Lepisiota canescens, has the potential of spreading all over the world and posing threats to other ants.

According to D Magdalena Sorger, a post-doctoral researcher with the North Carolina Museum of Natural Sciences and a key member of the team researching this ant species, the discovery is significant for two reasons. First, supercolony formation in ants is rare, with documented cases of only around 20 species worldwide. Second, other species in the Lepisiota genus have recently made headlines as worrisome invasive species, one in South Africa's Kruger National Park and another that shut down Australia's Darwin Port for several days. The team's findings, were published in Insectes Sociaux in November.

In Ethiopia, forests frequently surround Orthodox churches, some of which are more than 1,500 years old. These forests range in size from only a few hectares to more than 400 (~1,000 acres) and can be considered relict oases within largely barren land and agricultural fields. While L. canescens is native to the general region, it is now moving in large numbers into disturbed habitat like some of the more degraded church forests, but also beyond forest boundaries, into neighboring agricultural fields, and along recently constructed roads and other urban structures.

And that might be just the beginning, says lead author Sorger, who worked on this study while at North Carolina State University. "The species we found in Ethiopia may have a high potential of becoming a globally invasive species. Invasive species often travel with humans, so as tourism and global commerce to this region of Ethiopia continues to increase, so will the likelihood that the ants could hitch a ride, possibly in plant material or even in the luggage of tourists. All it takes is one pregnant queen. That's how fire ants started!"

Supercolonies are colonies that extend beyond just a single nest and can sometimes cover many thousands of miles. The strongest basis for describing a large colony as a supercolony is its capacity to expand its range without constraints. In this study, the scientists found several supercolonies of L canescens, the largest one spanning 38 km (24 miles). Molecular analysis of these ants showed lots of genetic diversity within and between supercolonies, indicating supercolony members were not more closely related and this species was native to the region. These are the largest documented supercolonies of a native ant species. Yet their exploding numbers, along with their observed ecological dominance as well as general nesting and diet, are all characteristics reminiscent of an invasive species.

 

'Vaccine Against HIV Closer To Reality', Say Researchers

Melbourne: In a significant progress towards the development of a vaccine against HIV, scientists have developed a new approach to help the immune system actively fight the virus in the body.

For the first time, researchers showed that a combined approach - using a common cold virus to introduce a vaccine into the body, as well as an injection of a DNA-based vaccine - may help protect against HIV in the gut and bodily cavities.

"With sexual activity being one of the primary methods of HIV transmission, it is necessary to try to protect those parts of the body that are most likely to encounter the virus first," said Branka Grubor-Bauk, from the University of Adelaide in Australia.

"A possible reason why previous HIV vaccine trials have not been successful is because of this lack of a front-line protection," Mr Grubor-Bauk said.

The laboratory studies, conducted so far in mice represent an important step forward in attempts to introduce a first line of defence against HIV at the site of infection.

"In mice, we delivered a rhinovirus (or common cold virus) inside the nose, and this virus had been altered to include HIV proteins," Mr Grubor-Bauk said.

"At the same time, the mice also received an injection into the skin containing a DNA-based vaccine. This approach resulted in very specific responses in the immune system," she said.

"This vaccine approach encompasses two different arms of the immune system: white blood cells that attack the HIV virus, and specific antibodies that recognise and shut down HIV-positive cells," she added.

"There is an element of HIV known as Tat that helps the virus to replicate quite rapidly," said Eric Gowans, professor at University of Adelaide.

The antibodies inhibit the Tat effect, preventing HIV from replicating itself, Mr Gowans added.

"Overall, we found that infection was considerably reduced in the mice we studied," he said.

The study appears in the journal Scientific Reports.

'Back to the Future' inspires solar nanotech-powered clothing

Marty McFly's self-lacing Nikes in Back to the Future Part II inspired a UCF scientist who has developed filaments that harvest and store the sun's energy -- and can be woven into textiles.

The breakthrough would essentially turn jackets and other clothing into wearable, solar-powered batteries that never need to be plugged in. It could one day revolutionize wearable technology, helping everyone from soldiers who now carry heavy loads of batteries to a texting-addicted teen who could charge his smartphone by simply slipping it in a pocket.

"That movie was the motivation," Associate Professor Jayan Thomas, a nanotechnology scientist at the University of Central Florida's NanoScience Technology Center, said of the film released in 1989. "If you can develop self-charging clothes or textiles, you can realize those cinematic fantasies -- that's the cool thing."

The research was published Nov. 11 in the academic journal Nature Communications.

Thomas already has been lauded for earlier ground-breaking research. Last year, he received an R&D 100 Award -- given to the top inventions of the year worldwide -- for his development of a cable that can not only transmit energy like a normal cable but also store energy like a battery. He's also working on semi-transparent solar cells that can be applied to windows, allowing some light to pass through while also harvesting solar power.

His new work builds on that research.

"The idea came to me: We make energy-storage devices and we make solar cells in the labs. Why not combine these two devices together?" Thomas said.

Thomas, who holds joint appointments in the College of Optics & Photonics and the Department of Materials Science & Engineering, set out to do just that.

Taking it further, he envisioned technology that could enable wearable tech. His research team developed filaments in the form of copper ribbons that are thin, flexible and lightweight. The ribbons have a solar cell on one side and energy-storing layers on the other.

Though more comfortable with advanced nanotechnology, Thomas and his team then bought a small, tabletop loom. After another UCF scientists taught them to use it, they wove the ribbons into a square of yarn.

The proof-of-concept shows that the filaments could be laced throughout jackets or other outwear to harvest and store energy to power phones, personal health sensors and other tech gadgets. It's an advancement that overcomes the main shortcoming of solar cells: The energy they produce must flow into the power grid or be stored in a battery that limits their portability.

"A major application could be with our military," Thomas said. "When you think about our soldiers in Iraq or Afghanistan, they're walking in the sun. Some of them are carrying more than 30 pounds of batteries on their bodies. It is hard for the military to deliver batteries to these soldiers in this hostile environment. A garment like this can harvest and store energy at the same time if sunlight is available."

There are a host of other potential uses, including electric cars that could generate and store energy whenever they're in the sun.

"That's the future. What we've done is demonstrate that it can be made," Thomas said. "It's going to be very useful for the general public and the military and many other applications."

Genetically engineering disease-fighting cells

The human body produces T cells to recognize and fight disease. Each T cell has a unique T cell receptor (or TCR) on its surface that surveils small fragments of proteins presented by other cells. Upon detecting evidence of cancer or infection, a subset of T cells binds the diseased cells and orchestrates their elimination. When tumors and infections cannot be eradicated naturally, researchers employ immunotherapies to boost the immune system's effectiveness.

By inserting genes encoding a tumor-specific TCR into a patient's T cells, researchers can engineer a large population of T cells to target tumor cells. This approach, called TCR gene therapy, has yielded clinical successes where conventional cancer treatments have failed. However, TCR gene therapy is not without risk. The introduced receptor can become tangled with the resident receptor in each engineered T cell, causing some of these cells to attack healthy cells. A new technique developed by Caltech researchers prevents this from happening, increasing the safety of TCR gene therapy.

The technique, called domain swapping, was developed in the laboratory of David Baltimore, president emeritus and the Robert Andrews Millikan Professor of Biology. A paper describing the findings appears in the November 8 issue of the journal eLife.

The specificity of the TCR in each T cell results from the pairing of two protein chains -- called an alpha chain and a beta chain -- each of which has constant domains (shared between all TCRs) and variable domains (unique to each T cell). Normally, each T cell encodes only one alpha chain and one beta chain, which pair to form a single TCR. In TCR gene therapy, the introduction of genes encoding a tumor-reactive TCR results in T cells that express two alpha chains and two beta chains, with four possible pairings. This non-physiological situation poses a risk of autoimmunity.

"As T cells are produced, the immune system 'auditions' them, eliminating those that react to healthy cells and selecting those with potential to recognize diseased cells," says Michael Bethune, senior postdoctoral scholar in biology and biological engineering, and lead author on the study. "However, in T cells engineered to express a second TCR, the introduced chains can mispair with the resident chains, resulting in TCRs with unintended and unpredictable specificity. These mispaired TCRs are not auditioned by the immune system, and some will target healthy cells causing autoimmunity." Indeed, up to 90 percent of mice administered TCR-engineered T cells develop autoimmune disease, and cultured human T cells that are engineered to express two TCRs also react with healthy cells.

The group's solution was to generate hybrid genes encoding TCR chains with their alpha and beta constant domains swapped in a compensatory fashion. When correctly paired, these domain-swapped TCRs retain all of the domains necessary to function. Indeed, the group found that domain-swapped TCRs and unmodified TCRs both function in human T cells, and they prevented tumor growth in mice to a similar extent. However, whereas unmodified TCRs mispaired with resident TCR chains in both mouse and human T cells, and caused autoimmunity in mice, domain-swapped TCRs did not.

"Mispairing between domain-swapped chains and resident chains results in TCRs that lack domains needed for functional assembly of the TCR complex," Bethune says. "This ensures that only correctly paired domain-swapped TCRs function at the surface of the cell."

In addition to preventing mispairing, domain-swapped TCRs highlight a surprising robustness to the function of the TCR complex. The Caltech group teamed with Mike Kuhns at the University of Arizona to determine that domain-swapped TCRs assemble in a similar manner to unmodified TCRs despite significant structural rearrangement of the constituent protein chains. Domain-swapped TCRs may be useful tools for further study of the structure and function of the TCR complex.

Finally, in collaboration with Wolfgang Uckert at the Max Delbrück Center for Molecular Medicine in Berlin, the researchers showed that domain-swapped TCRs were expressed at higher levels on the T cell surface when the resident TCR genes were silenced.

"Our paper focuses on the increased safety afforded by domain-swapping, but combining these two solutions may result in a therapy with improved safety and efficacy compared to current practice," Bethune says.

November’s supermoon will be bigger than it has been since 1948

November’s full moon is special. Not only is it a supermoon — which appears larger than a “regular” full moon — it will be the closest such moon to Earth since January 1948. We won’t see the full moon this close again until Nov. 25, 2034, according to NASA.

In the middle of November, we savor the splendor of a full moon. With any luck, this awe-inspiring moon will lure people outside to breathe the crisp air of the autumnal night sky, spark people to hold hands and spur interest in relishing the heavens.

The moon officially becomes full on Monday at 8:52 a.m. — it won’t be visible on the East Coast at the exact moment of fullness, but it will on the West Coast.

Since the moon’s orbit around Earth is an elliptical shape, there are times when our lunar companion is closest to Earth. This is called perigee. This month, the perigee occurs Nov. 14 at about 6 a.m. — within two hours of the moon becoming officially full — making this fun event an extra-super, perigee full moon.

Astrologer Richard Nolle defined a supermoon in 1979, but the term has really taken off in the past few years. Sometimes it seems as if every moon is a supermoon. Nolle said that a supermoon is a new or full moon that occurs when the moon is within 90 percent of its closest approach to Earth in a given orbit.

The distance between Earth and the moon can range from 221,208 miles at its closest possible point to 252,898 miles at its farthest. That’s a difference of nearly 32,000 miles. This month, it gets close at 221,524 miles between Earth and the moon — just 316 miles from its nearest possible location.

The supermoon isn’t just a fun sight for photographers and skywatchers — it has an actual impact on the coastline. Every year from November through February, the highest tides — called “king tides” — sweep onto the shores during full moons. This is due to the combination of gravity from the moon and sun being the closest to Earth as they will be all year. The tides get even higher during “supermoons” simply because the moon is closer to Earth.

On Sunday afternoon, the nearly-full moon rises at 4:43 p.m. in Washington, while the sun sets at 4:55 p.m. The following morning, the moon sets at 6:36 a.m. — so if you scoot out of bed around 5 a.m., you’ll see the moon low in the western sky plump and full. The full moon rises Monday evening at 5:30 p.m., so look for it close to the eastern horizon.

For any location in the United States or abroad, the Naval Observatory provides rise and set times for the moon and sun.

In October, NASA said that “the perigee full moon can be as much as 14 percent larger and 30 percent brighter than an apogee full moon.” The NASA team goes on to explain, “Hanging high overhead with no reference points to provide a sense of scale, one full moon looks much like any other.”

In other words, for the human eye, it is difficult to perceive the difference between a supermoon and any other.

The next perigee full moon occurs Dec. 14 — the third such moon in an October-November-December lunar trifecta. After that, there will be a perigee full moon on Jan. 1-2, 2018 — when the moon and the Earth will be 221,559 miles apart.

Scientists show how mutation causes incurable premature aging disease

Scientists have demonstrated how a mutation in a specific protein in stem cells causes an incurable premature aging disease called dyskeratosis congenita, and were able to introduce the mutation into cultured human cells using gene editing technology.

The study findings provide a drug target for the disease, said lead study author Jayakrishnan Nandakumar, assistant professor of molecular, cellular and developmental biology at the University of Michigan.

The mutation compromises the function of an enzyme known as telomerase, which fuels stem cell division, he said. Stem cells must divide to repair old tissue.

This mutation, which occurs in the telomere protein TPP1, causes stem cells to slow or stop dividing in people with this rare, incurable disease. This can cause tissue breakdown, premature aging, bone marrow failure, cancer and even death.

Nandakumar and his U-M colleagues are believed to be the first to use genome editing technology called CRISPR/CAS9 to introduce a dyskeratosis congenita mutation into human cells.

This gene editing technology is often described as a pair of molecular scissors, because it cuts DNA in precise locations to allow for additions, deletions and replacements of DNA near the cut. The acronyms stand for Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (CAS9).

The patient relevant to the study had one mutant gene, but also one normal TPP1 gene, yet still suffered from the disease. Nandakumar's group wanted to know if introducing one copy of the mutant TPP1 gene into cultured human cells using the CRISPR/CAS9 gene editing technology would compromise telomerase function in those cells, too.

It did, which meant that the mutation caused the disease.

"We envision that correcting the mutation in the stem cells of the patient will reverse the cellular symptoms of the disease, if and when such technology becomes available," Nandakumar said.

Understanding how the TPP1 mutation works also has implications for treating cancer patients, he said. This is because while the TPP1 mutation inhibits stem cell division in people with dyskeratosis congenita, normal TPP1 fuels cell division in people with cancer.

Earth-like planets in solar system ‘habitable zones’ to be photographed for 1st time

Scientists are planning to launch a new telescope capable of photographing Earth-like planets in a nearby solar system which could be home to alien life.

The privately-financed initiative, called Project Blue, hopes to take the first photo of a planet in the so-called ‘habitable zone’ – the area around a star in which life is able to exist.

Led by the US-based BoldlyGo Institute, a non-profit scientific organization, the project will focus on nearby solar system Alpha Centauri and aims to have built the telescope by 2020 at an estimated cost of $25 million to $50 million.

BoldlyGo Institute CEO John Morse, who was formerly director of astrophysics at NASA, described the proposed telescope as the “holy grail of exoplanet” research.

Morse said the project will focus on Alpha Centauri partly because it is close to the Earth, but also because there’s a greater chance of photographing a habitable planet.

The fact that you do have two stars [at Alpha Centauri], it’s like two coin flips,” Morse told Popular Science.

There’s four possible outcomes and only one of them is nothing, so we’re hoping that at least one of the stars will have terrestrial planets around it, and possibly both, which would be an amazing discovery.”

Although the solar system is near to Earth, such distance is relative to the vastness of the universe.

Alpha Centauri is a mind-boggling 4.22 light years away, which means it would take humans about 100 years to get there if traveling at a speed of 13,411 kilometers per second.

Project Blue hopes to photograph this enormous distance with a telescope about the size of a small washing machine and with a mirror only 50cm across.

The telescope will use a coronagraph to block out light from more distant stars, allowing the lens to capture clear photographs of planets that would otherwise be drowned out in the brightness of nearby stars.

Although still in its early stages, the project hopes to get cash support from project partners such as the SETI Institute and will also use crowdfunding to pay for initial design work.

Morse hopes the project will inspire future missions to study Earth-like planets.

If we discover a pale blue dot around one of the Alpha Centauri stars, the urgency to build larger facilities, to do more characterization of that and eventually hope to see weather patterns or mountain ranges or continents, we’ll see a lot more interest in doing that kind of thing,” Morse told Popular Science.

That’s the impact that we want this to have.”

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