Long-acting drug effectively prevents HIV-like infection in monkeys

The new drug cabotegravir (in vials above) has been shown to protect monkeys from infection by an HIV-like virus, and a clinical trial testing cabotegravir's safety and acceptability has begun. Unlike other preventive treatments, it would require only one injection every three months.
Credit: Zach Veilleux / The Rockefeller University

A regime of anti-HIV drugs -- components of regimens to treat established HIV infection -- has the potential to protect against infection in the first place. But real life can interfere; the effectiveness of this prophylactic approach declines if the medications aren't taken as prescribed.

HIV researchers hope a new compound, known as cabotegravir, could make dosing easier for some because the drug would be administered by injection once every three months. A clinical trial testing long-acting cabotegravir's safety and acceptability has already begun at multiple U.S. sites including The Rockefeller University Hospital. Meanwhile two new studies, including one conducted by researchers at the Aaron Diamond AIDS Research Center (ADARC) and Rockefeller University, published today (January 15) in Science Translational Medicine, show that long-acting cabotegravir injections are highly protective in a monkey model of vaginal transmission of a virus similar to HIV.

"Clinical trial results have demonstrated that the effectiveness of preventive oral medications can range with results as high as 75 percent effective to as low as ineffective, and a lot of that variability appears to hinge on the patient's ability to take the pills as prescribed," says study researcher Martin Markowitz, a professor at Rockefeller University and ADARC. "Long acting cabotegravir has the potential to create an option that could improve adherence by making it possible to receive the drug by injection once every three months."

Developed by ViiV Healthcare and GlaxoSmithKline, and previously known as GSK744 LA, cabotegravir is an antiretroviral drug. Antiretrovirals interfere with HIV's ability to replicate itself using a host cell and they are used to treat an HIV infection or to prevent those at high risk from acquiring it in the first place.

Cabotegravir belongs to a group of antiretrovirals that target integrase, an enzyme the virus uses to integrate itself into the cell's genome. This compound is a relative of an already FDA-approved integrase inhibitor, dolutegravir, but with chemical properties that allow it to be formulated into a long-acting suspension for injection.

A previous study by the ADARC and Rockefeller team in collaboration with ViiV Healthcare and GSK found long-acting cabotegravir could protect male rhesus macaque monkeys from exposure to a virus related to HIV. Following up on these results, a phase 2 clinical trial is now underway in a group of 120 men at low risk of infection. Before cabotegravir's effectiveness in high risk individuals can be tested, trials must show that study participants tolerate the drug well and find the quarterly injections, which are a novel approach to HIV prevention, acceptable.

Both new animal studies were conducted with women in mind; in 2013 women accounted for 47 percent of new HIV infections worldwide according to the Joint United Nations Programme on HIV and AIDS. Working separately, two teams tested the drug's ability to block vaginal transmission in two species of monkeys with different breeding cycles and susceptibility to infection.

First author Chasity Andrews, a postdoctoral fellow at ADARC and Rockefeller, and colleagues at ADARC, the Tulane Regional Primate Center and ViiV/GSK, studied female rhesus macaques treated with progesterone to increase their susceptibility to the virus. They found injections of long acting cabotegravir were 90 percent effective at protecting the monkeys from repeated high-dose exposures to the virus.

Meanwhile, the complementary study conducted by researchers at the CDC and ViiV/GSK found female pigtail macaques injected with cabotegravir were completely protected against multiple exposures to the virus.

"While we are still a long way off from showing that this drug works for HIV prevention in humans, our hope is that it may one day offer high risk women, as well as men, an additional option for HIV prevention," Markowitz says. "One of the lessons we have learned from contraception is the more options available, the better. We are hoping for the same in HIV prevention -- more options and better results."

Source: Rockefeller University

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CASIS research set for launch aboard SpaceX mission to space station

The Bone Densitometer developed by Techshot, Inc. will enable X-ray testing for research studies aboard the International Space Station. Credit: CASIS

This fall marks another commercial cargo flight to the International Space Station. In September, SpaceX's Dragon spacecraft is scheduled to blast off to the orbital laboratory carrying supplies and investigations as part of the company's fourth contracted mission to the complex.

Included in the cargo will be the third suite of research investigations sponsored by the Center for the Advancement of Science in Space (CASIS). With the role of managing the U.S. National Laboratory on the space station, CASIS is responsible for brokering and facilitating research investigations on the station with clear Earth applications and benefits.

The latest collection of CASIS-sponsored research, termed Advancing Research Knowledge (ARK)-2, centers heavily on life sciences. Studies include those focused on drug development, disease understanding and validation testing. Each investigation will use the unique conditions aboard the space station to advance researchers' understanding in those areas of study.

Additionally, CASIS and NASA have partnered with Techshot Inc., of Greenville, Indiana, to develop a new hardware device capable of assisting with research that may improve understandings of muscle wasting and diseases like osteoporosis.

The CASIS-sponsored hardware and life science investigations destined for the space station's national laboratory include the Bone Densitometer, which will be the first X-ray machine installed on the space station. A joint project between CASIS, NASA and Techshot, the facility will be instrumental in conducting rodent research on station. The Bone 

Densitometer will allow astronauts to examine bone density of model organisms in space through the use of Dual-Energy X-ray Absorptiometry (DEXA) technology. In short, researchers will be able to assess bone density loss by measuring energy levels absorbed by bones via the device.

The Rodent Research-1 investigation kicks off a series of NASA and CASIS-sponsored investigations focused on rodent research aboard the space station. The study will be the first to use the Bone Densitometer in an effort to help scientists examine the effects of long duration spaceflight. There are numerous applications to these investigations including studying bone loss, muscle atrophy and cardiovascular anomalies. However, the primary focus of this inaugural mission will be to assess the operational capabilities of the new hardware designed for these investigations.

The Drug Metabolism study will assist researchers in the area of drug development and human biology. This investigation is led by a scientist from the U.S. Department of Veteran Affairs, Dr. Timothy Hammond, who is looking to study yeast cells in microgravity. The goal of this investigation is to explore the changes in these cells in space to improve drug development for various diseases, including cancer therapeutics.

The Protein Crystal Optimization study is an investigation aiming to leverage the unique location of the space station to examine the internal structure of three medically important proteins. The space environment should allow researchers to grow the selected protein crystals to an optimal size and quality to allow for closer examination via neutron diffraction. This protein crystal growth in microgravity may reveal new characteristics that are masked by gravity on Earth. By studying these three proteins, medically relevant to salmonella infection, peptic ulcer disease, and biomarkers for heart attack and liver disease, researchers can apply insights towards improved treatments.

A New Era In Commercial Use of the Space Station

The space station's national laboratory affords researchers the ability to conduct experiments in a distinctive environment with factors and variables that are near impossible to replicate on the ground. With access to our nation's only orbiting laboratory, CASIS works with new and non-traditional users to take advantage of this resource. A great example of novel commercial research heading to station is the Cobra Puma Golf investigation.

The Cobra Puma Golf-electroplating investigation, also launching aboard SpaceX, is a materials science investigation sponsored by CASIS in collaboration with COBRA PUMA Golf (CPG). The CPG research and development team will examine the impacts of microgravity on electroplating -- the process of coating a metallic surface using an electric current. The study will test a variety of coating substances on materials used in golf equipment manufacturing. The insight gained from this investigation will aid CPG in identifying improved material development techniques.

CPG's project is another example of a commercial user leveraging the capabilities of the ISS National Lab to advance ground research. Through brokering research investigations with commercial companies, CASIS hopes to demonstrate the space station is not only a test-bed for groundbreaking research and development, but a unique laboratory that can help differentiate investigations initiatives from ground-based studies.

The mission is another milestone for the space community, showcasing how commercial endeavors can work hand-in-hand with research goals. The studies of ARK-2 exemplify the diverse possibilities for the space station and users of the research platform. From commercial launch providers that transport investigations to space, to commercial researchers looking to use the national laboratory, science in space is good for life on Earth.

Source: NASA

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Primates indispensable for regeneration of tropical forests

Moustached tamarins (Saguinus mystax) contribute crucially to the seed dispersal of the neotropical tree Parkia panurensis. Credit: Julia Diegmann

Primatologist and plant geneticists have studied the dispersal of tree seeds by New World primates.

Primates can influence seed dispersal and spatial genetic kinship structure of plants that serve as their food source. This is the result of a cooperation project of behavioral ecologist Eckhard W. Heymann from the German Primate Center (DPZ) with plant geneticists Birgit Ziegenhagen and Ronald Bialozyt from the Philipps-University Marburg. This study was funded by the German Research Foundation.

At the DPZ-field station Estación Biológica Quebrada Blanco in the Peruvian Amazonian lowlands, scientists studied how feeding, sleeping, and ranging habits of two species of New World monkeys affect the dispersal of the neotropical legume tree Parkia panurensis. For this, the researchers observed a group of Brown-mantled tamarins (Saguinus nigrifrons) and Moustached tamarins (Saguinus mystax), who jointly moved through home ranges in search of edible plants which included Parkia trees.

Fruits from these trees are pods that contain 16 to 23 seeds, each of which is surrounded by edible gum. The monkeys feed on the gum content of the pods and at the same time swallow the Parkia seeds which are later defecated intact in a different area.

During behavioral observations, researchers recorded the food intake of tamarins as well as the location of the Parkia trees that they visited. In addition, they collected faecal samples of the tamarins that contained seeds. "With the help of genetic analyses of the DNA found in the seed coat, which is of maternal origin, we could make an exact assignment of the corresponding "mother tree" for the seeds," says Eckhard W. Heymann from the DPZ. "This allowed us to determine how far Parkia seeds were dispersed by the monkeys."

In order to analyze the effect of seed dispersal by monkeys on a spatial genetic level, the scientists examined three different developmental stages of the trees. In addition to the seeds that contain the plant embryo, they collected leaves from young and mature Parkia trees in the home range of tamarins. "With the help of analysis from microsatellites, short repeated DNA sequences, we were able to identify genetic similarities of individual trees," says Heymann.

The analysis of the spatial genetic structure of the Parkia population revealed a significant genetic relationship of the plant embryos and young trees within a radius of 300 meters, which coincides with the distance within which most seeds are dispersed by the tamarins. For mature trees, the relationship was reduced to a radius of only up to 100 meters.

"In tropical rain forests, the seeds of 80 to 90 percent of trees and lianas are dispersed by animals. In addition to primates, birds and bats are the major animal groups that are responsible for seed dispersal," says behavioral ecologist Heymann. "For the plants, transport of their seeds is extremely important. As sedentary organisms, this is the only way that their offspring -- the embryos contained in the seeds -- can reach appropriate sites for germination and growth. Furthermore, this reduces the density-dependent mortality which occurs when the seeds fall under the mother plants," says Eckhard W. Heymann. Fruit-eating primates such as tamarins are therefore invaluable to the natural regeneration and diversity of ecosystems in which they live.

Source: German Primate Center

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