My newest story for the Medical Post/Canadian Healthcare Network -- on Cancer research in #space. Free to #doctors and #pharmacists in #Canada. Here is the first section.

AUGUST 2024 -- Cancer treatments could be from out of this world. Literally.

The low gravity environment of space offers various qualities that can speed up research on how cancer cells grow and behave, as well for developing new molecules for treating cancer.

Indeed, one advance already used in clinical practice is an improved version of the drug Keytruda (pembrolizumab) which is used for several cancers.

Prior to work on the International Space Station (ISS), Keytruda was administered via a line or port, said Bill Nelson, an administrator at the U.S. National Aeronautics and Space Administration (NASA)

But “aboard the station, our astronauts were able to develop methods for protein crystal growth that made it possible to administer Keytruda in a new way, by an IV injection,” which can be administered in as little as 20 minutes, he said. Dr. Nelson was a panelist on a recent virtual event hosted by NASA on cancer research in space.

Last year, NASA got a boost in funding for space-based cancer research as part of the U.S> President Joe Biden's Moonshot #Cancer program. The ISS orbits Earth every 90 minutes, and since November 2000, nearly 4,000 different experiments from various disciplines representing more than 5,000 researchers from over 100 countries have been conducted. This includes commercial, academic and government users.

And, it offers a unique environment for conducting #research, with a major area of interest being medicine. Originally, a part of that was to study how space affects astronauts. #Microgravity leads to bones loss, changes in vision and eyeball shape, has cardiovascular effects and more. Plus there are the effects of radiation.

As an example, in 2009 Canadian astronaut Bob Thirsk performed experiments and gathered data for the Canadian #Cardiovascular and Cerebrovascular Control (CCISS) project. CCISS was launched largely because of the dizziness and faintness phenomenon experienced by astronauts.

While these are topics explored in the interest of space travel, there are a huge number of applications to people on Earth.

“We explore space to explore the heavens and to improve life here on Earth—that includes attacking this dread disease (cancer),” said Dr. Nelson stated— and that’s why #NASA is involved in president’s Moonshot program.

In brief there are three categories of research that work well in space :

- protein crystal growth
- nanoparticle and tissue engineering
- stem cells.

In many ways, it’s a better place to work with and grow 3D tissue models.

In Earth’s gravity, “it’s harder to grow 3D models of certain tissues, stem cells, and many organ tissues also known as organoids. But in microgravity, we’re able to grow these kinds of tissues and use them as testing grounds for stem cell related cancer screening and cancer detection. We can also test different drugs on cancer infested organoids,” said Dr. Nelson.

According to Michael Roberts, the ISS currently has multiple experiments from various companies and academic investigators that are focused on improvements in nanoparticle drug delivery. Roberts is chief scientific officer of the ISS and the vice-president at the Center for the Advancement of Science in Space.

Nanoparticles can be used to improve the targeting efficiency of cancer drugs, chemotherapies or cell based therapies. And they can be used “as frameworks or structures on which you can build, for example, cartilage on which to repair tissue damage.”...

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https://canadianhealthcarenetwork.ca/cancer-research-blasts-materials-behave-differently-lower-gravity-allowing-accelerated-research

Part of my article about new research looking at Laughing Gas and other Anesthetics for Depression.In the #Medical Post (sorry, only MD and #pharmacists in Canada can get accounts).

"JULY 2024 -- While the nickname ‘laughing gas’ sounds like something that might cheer people up, it’s only recently that it’s been taken seriously as a possible tool for treatment-resistant depression.

Indeed, nitrous oxide is one of several anesthetics generating excitement as new ways to treat depression. Nitrous oxide, ketamine, propofol, sevoflurane and isoflurane are all being investigated for possible roles in clinical depression. Ketamine is already used in many places for this purpose.

When it comes to anesthetics for #depression “right now ketamine is the rock star, but nitrous oxide is very promising,” said Dr. Beverley Orser, an anesthesiologist and professor of #medicine at the University of Toronto and coauthor of a paper in Anesthesiology discussing general anesthetic drugs for depression.

There are multiple reasons why anesthetic drugs show promise—leading to a lag in considering them for this indication. Intriguingly, they target different receptors in the brain than current antidepressants.

Generally, #antidepressants (including selective serotonin reuptake inhibitors) target the monoamine system. They “typically require weeks or months to take effect, and are associated with adverse effects that reduce drug adherence,” the paper said.

#Anesthetics including ketamine and nitrous oxide primarily work by blocking N-methyl D-aspartate (NMDA) to lead to loss of consciousness and #analgesia—though they also target additional receptors. But dysregulation of the NMDA system can contribute to mood disorders and anxiety, suggesting where possible connections between anesthesiology and psychiatry may exist.

“Currently, it remains unclear whether the antidepressant properties of general anesthetic agents result from a single common pathway or multiple different mechanisms. All anesthetic drugs generally modify the balance between excitation and inhibition in the central nervous system, and regional changes in excitation and inhibition balance have been described in the context of major depressive disorder,” the paper said.

It all started with ketamine which was discovered in 1956. Long used for sedation and pain management, it wasn’t until the year 2000 that it leapt to the fore as a possible treatment for depression. That’s when a small placebo controlled trial of seven patients with major depressive disorder (MDD) were given a single dose of either placebo or a low dose of ketamine.

The results surprised everyone. The patients given ketamine not only improved quickly, but the effect lasted for several days. Since then, multiple trials have been conducted, the use of #ketamine for MDD has become relatively widespread, and in 2019 the FDA approved esketamine for depression.

Esketamine is an intranasal version of ketamine that is combined with a conventional oral antidepressant. Because of adverse side-effects, its approval requires that it be given in a restrictive clinical setting where patients are under the supervision of physicians. However, the National Health Service in Great Britain rejected its approval in that country because of concerns about possible side effects.

“What’s clear is these drugs are having rapid but sustained antidepressant properties, which persist long after the drug and the drug metabolites have been eliminated. But what’s equally interesting is that they don’t seem to have the same effect on the normal healthy brain,” Dr. Orser said. They may not be as effective in people with milder depression.

It also leads to the idea that “there is something that is dysregulated in depression and the drugs are righting a wrong. That’s very interesting because the drugs are also providing insights into the biology of the dysregulation that’s causing depression,” Dr. Orser told the Medical Post.

That there are lingering drug effects has upset some traditional ideas in anesthesiology, such as the belief that once an anesthetic drug has dissipated, it is eliminated from the brain and the brain goes back to baseline state. Recent studies are showing there are longer effects, as well possible increased risk of neurocognitive changes and possibly dementia in older patients who get general anesthesia.

Whether it’s laughing gas or ketamine, the drugs need to be treated with respect because of various risks associated with their administration. Even if the doses are substantially smaller than what’s used for anesthesia..."

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https://canadianhealthcarenetwork.ca/no-laughing-matter-laughing-gas-treating-depression