Here’s Something Cool To Do With Your Leftover Candy Corn – All You Have To Do Is Head To Space.

Dive deep into Episode 05 of #ShelfLife to discover the various technologies that have helped humans map the sky around us for eons. 

From sundials to mega-powered modern telescopes, tools for stargazing allow us to understand the universe—and our place within it. Season 2 begins on November 1. 

Manufacturing Dopamine in the Brain with Gene Therapy

Parkinson’s patients who take the drug levodopa, or L-Dopa, are inevitably disappointed. At first, during a “honeymoon” period, their symptoms (which include tremors and balance problems) are brought under control. But over time the drug becomes less effective. They may also need ultrahigh doses, and some start spending hours a day in a state of near-frozen paralysis.

A biotech company called Voyager Therapeutics now thinks it can extend the effects of L-Dopa by using a surprising approach: gene therapy. The company, based in Cambridge, Massachusetts, is testing the idea in Parkinson’s patients who’ve agreed to undergo brain surgery and an injection of new DNA.

Parkinson’s occurs when dopamine-making neurons in the brain start dying, causing movement symptoms that afflicted boxing champ Muhammad Ali and actor Michael J. Fox, whose charitable foundation has helped pay for the development of Voyager’s experimental treatment.

The cause of Parkinson’s isn’t well understood, but the reason the drug wears off is. It’s because the brain also starts losing an enzyme known as aromatic L-amino acid decarboxylase, or AADC, that is needed to convert L-Dopa into dopamine.

Voyager’s strategy, which it has begun trying on patients in a small study, is to inject viruses carrying the gene for AADC into the brain, an approach it thinks can “turn back the clock” so that L-Dopa starts working again in advanced Parkinson’s patients as it did in their honeymoon periods.

Videos of patients before and after taking L-Dopa make it obvious why they’d want the drug to work at a lower dose. In the ‘off’ state, people move in slow motion. Touching one’s nose takes an effort. In an ‘on’ state, when the drug is working, they’re shaky, but not nearly so severely disabled.

“They do well at first but then respond very erratically to L-Dopa,” says Krystof Bankiewicz, the University of California scientist who came up with the gene-therapy plan and is a cofounder of Voyager. “This trial is to restore the enzyme and allow them to be awakened, or ‘on,’ for a longer period of time.”

Voyager was formed in 2013 and later went public, raising about $86 million. The company is part of a wave of biotechs that have been able to raise money for gene therapy, a technology that is starting to pay off: after three decades of research, a few products are reaching the market.

Unlike conventional drug studies, those involving gene therapy often come with very high expectations that the treatment will work. That’s because it corrects DNA errors for which the exact biological consequences are known. Genzyme, a unit of the European drug manufacturer Sanofi, paid Voyager $65 million and promised hundreds of millions more in order to sell any treatments it develops in Europe and Asia.

“We’re working with 60 years of dopamine pharmacology,” says Steven Paul, Voyager’s CEO, and formerly an executive at the drug giant Eli Lilly. “If we can get the gene to the right tissue at the right time, it would be surprising if it didn’t work.”

But those are big ifs. In fact, the concept for the Parkinson’s gene therapy dates to 1986, when Bankiewicz first determined that too little AADC was the reason L-Dopa stops working. He thought gene therapy might be a way to fix that, but it wasn’t until 20 years later that he was able to test the idea in 10 patients, in a study run by UCSF.

In that trial, Bankiewicz says, the gene delivery wasn’t as successful as anticipated. Not enough brain cells were updated with the new genetic information, which is shuttled into them by viruses injected into the brain. Patients seemed to improve, but not by much.

Even though the treatment didn’t work as planned, that early study highlighted one edge Voyager’s approach has over others. It is possible to tag AADC with a marker chemical, so doctors can actually see it working inside patients’ brains. In fact, ongoing production of the dopamine-making enzyme is still visible in the brains of the UCSF patients several years later.

It is possible to tag AADC with a marker chemical, so doctors can actually see it working inside patients’ brains. Image Source: MIT Technology Review.

In some past studies of gene therapy, by contrast, doctors had to wait until patients died to find out whether the treatment had been delivered correctly. “This is a one-and-done treatment,” says Paul. “And anatomically, it tells us if we got it in the right place.”

A new trial under way, this one being carried out by Voyager, is designed to get much higher levels of DNA into patients’ brains in hopes of achieving better results. To do that, Bankiewicz developed a system to inject the gene-laden viral particles through pressurized tubes while a patient lies inside an MRI scanner. That way, the surgeon can see the putamen, the brain region where the DNA is meant to end up, and make sure it’s covered by the treatment.

There are other gene therapies for Parkinson’s disease planned or in testing. A trial developed at the National Institutes of Health seeks to add a growth factor and regenerate cells. A European company, Oxford BioMedica, is trying to replace dopamine.

Altogether, as of this year, there were 48 clinical trials under way of gene or cell replacement in the brain and nervous system, according to the Alliance for Regenerative Medicine, a trade group. The nervous system is the fourth most common target for this style of experimental treatment, after cancer, heart disease, and infections.

Voyager’s staff is enthusiastic about a study participant they call “patient number 6,” whom they’ve been tracking for several months—ever since he got the treatment. Before the gene therapy, he was on a high dose of L-Dopa but still spent six hours a day in an “off” state. Now he’s off only two hours a day and takes less of the drug.

That patient got the highest dose of DNA yet, covering the largest brain area. That is part of what makes Voyager think higher doses should prove effective. “I believe that previous failure of gene-therapy trials in Parkinson’s was due to suboptimal delivery,” says Bankiewicz.

Image Credit: L.A. JOHNSON

Source: MIT Technology Review (by Antonio Regalado)

The race to map the human body — one cell at a time

The first time molecular biologist Greg Hannon flew through a tumour, he was astonished — and inspired. Using a virtual-reality model, Hannon and his colleagues at the University of Cambridge, UK, flew in and out of blood vessels, took stock of infiltrating immune cells and hatched an idea for an unprecedented tumour atlas.

“Holy crap!” he recalls thinking. “This is going to be just amazing.”

On 10 February, the London-based charity Cancer Research UK announced that Hannon’s team of molecular biologists, astronomers and game designers would receive up to £20 million (US$25 million) over the next five years to develop its interactive virtual-reality map of breast cancers. The tumour that Hannon flew through was a mock-up, but the real models will include data on the expression of thousands of genes and dozens of proteins in each cell of a tumour. The hope is that this spatial and functional detail could reveal more about the factors that influence a tumour’s response to treatment.

The project is just one of a string that aims to build a new generation of cell atlases: maps of organs or tumours that describe location and make-up of each cell in painstaking detail.

The Hubble Space Telescope captured this picture of the wispy remains of a supernova explosion. The dust cloud in the upper center of the picture is the actual supernova remnant. The dense concentration of stars in the lower left is the outskirts of star cluster NGC 1850. Full resolution picture here. More info here. Credit: NASA, ESA, Y.-H. Chu (Academia Sinica, Taipei)

Meet the all-female team of coders that brought us Apollo 11.

In 1969, the world watched as Neil Armstrong marked his historic achievement with the words, “That’s one small step for man, one giant leap for mankind.” His now-famous transmission was heard around the globe thanks to NASA’s Deep Space Network, which made communication from outer space possible.

That network was built by a woman named Susan Finley. She was part of an all-female team of coders whose work was integral to the success of the Apollo 11 mission. Science writer Nathalia Holt brings us their stories in her book, Rise of the Rocket Girls: The Women Who Propelled Us from Missiles to the Moon to Mars.

Listen to their story here.

[Images via NASA]

Today is World Blood Donor Day – here’s a look at some blood chemistry! More info/high-res image: http://wp.me/s4aPLT-blood

For those poorly informed (educated) who insist that vaccines are just the same as catching the illness…. This is just one example of why that is not true.

Breakthrough for vaccine research: Mucosa forms special immunological memory

If a vaccine is to protect the intestines and other mucous membranes in the body, it also needs to be given through the mucosa, for example as a nasal spray or a liquid that is drunk. The mucosa forms a unique immunological antibody memory that does not occur if the vaccine is given by injection. This has been shown by a new study from Sahlgrenska Academy published in Nature Communications.                                

Immunological memory is the secret to human protection against various diseases and the success of vaccines. It allows our immune system to quickly recognize and neutralize threats. “The largest part of the immune system is in our mucosa. Even so, we understand less about how immunological memory protects us there than we do about protection in the rest of the body. Some have even suggested that a typical immune memory function does not exist in the mucosa,” says Mats Bemark, associate professor of immunology at Sahlgrenska Academy, University of Gothenburg.

After extensive work, the research team at Sahlgrenska Academy can now show that this assumption is completely wrong.

Mats Bemark et al. Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization, Nature Communications (2016). DOI: 10.1038/ncomms12698

It’s time for #TrilobiteTuesday! During their lengthy trek through time, trilobites existed in an almost dizzying array of sizes and shapes. Perhaps no other creature in the entire history of the earth has ever displayed the diversity of design shown by these singularly distinctive arthropods. But at their heart (and yes, trilobites apparently did possess primitive but effective cardio-respiratory systems), they were all remarkably similar. Named not, as is generally surmised, for their three main body segments – cephalon (head), thorax (body) and pygidium (tail) – but rather for the three lobes that longitudinally divided their dorsal exoskeleton. Whether they were Cambrian Olenellids – such as this Olenellus romensis from Alabama – or Devonian Phacopids, most trilobites presented a fundamentally analogous body design. Such characteristics as occipital lobes, anterior margins and facial sutures (which allowed early trilobites to shed their molting shell), were shared by the majority of trilobite species, as were such exotic-sounding features as axial rings, articulating facets and pleural spines. 

Molecule of the Day: Limonene

d-Limonene (C10H16) is a naturally occurring, chiral cyclic hydrocarbon with an orangey scent, and is found in citrus peels and citrus essential oils. It is a colourless liquid that is immiscible with water at room temperature and pressure. 

Limonene undergoes reactions typical of an alkene, such as electrophilic addition and oxidative cleavage. It is biosynthesised from geranyl pyrophosphate in plants, and is classified as a terpene.

While limonene can be synthesised in the lab, as shown below, it is produced industrially from the steam distillation of citrus peels due to its natural abundance. Furthermore, citrus peels are a by-product of orange juice manufacturing, which makes it environmentally-friendly.

Limonene is commonly used in perfumes, soaps, and foods due to its fresh, citrus-like scent, and can also act as a pesticide. It is gaining prominence as an environmentally-friendly solvent and paint stripper. However, it is also a skin sensitiser, as it can dissolve the oils and fat underneath the skin!

Links:

Extraction of limonene from orange peels - YouTube

Dissolving styrofoam using limonene - YouTube