The Sequence 1/16-1/22
Routine Genetic Testing of Viral Infection Samples, Building Blocks of DNA and RNA Identified in Meteorites, Treatment Approved for Alzheimer’s Disease, Polygenic Risk Scores and Gestational Diabetes
Routine genetic testing of viral infection samples
The Respiratory Virus and Microbiome Initiative has proposed routine genetic testing of virus samples from people with severe respiratory infections, such as flu and RSV, starting this year.
Cool. Why would they do that?
A few reasons. Firstly, to track the viruses. During the COVID-19 pandemic, we have been able to predict oncoming waves of new COVID variants by sequencing the viral genomes of COVID samples as people get tested. Think: in the U.S., we knew the Omicron variant was coming our way last summer before it actually did. How? Because COVID viral samples were being sequenced, and scientists saw the new strain clearly ticking up in numbers. On a smaller scale, tracking viruses could mean understanding in which hospitals or communities people are being infected, allowing for earlier stop of the spread before it begins.
Secondly, to provide the right treatments to the affected individuals. Using COVID as an example again, some antibody treatments for COVID-19 may be less effective against newer variants. If healthcare providers know what variant of a virus someone has, they can give the right treatment.
Thirdly, to lead to more efficient vaccines. If we undertstand the molecular properties of the newest viral variants out there, we can more appropriately design the next vaccine or booster against them.
Finally, to tell us about new viruses that may be emerging. Remember when COVID-19 was brand new and never-before-seen in humans? In the future, we may be able to tackle viruses at this stage, before they cause a pandemic.
Awesome. What’s the takeaway?
This type of global initiative could could lead to better treatments and vaccines, as well as earlier warning of dangerous new outbreaks. Keep in mind that this is in its initial stages, and kinks will need to be worked out- sequencing any of a dozen or so different types of viruses that might be present in a sample is technically more difficult than just sequencing one, and is especially difficult to do inexpensively. Overall, though, this is an important initiative that could make a world of an impact for our future health.
Pieces of the Murchison meteorite are on display in Melbourne Museum's Dynamic Earth exhibition. Image Credit: Museums Victoria
Building blocks of DNA and RNA identified in meteorites
In a careful extraction of particles from two Murchison meteorite specimens, Oba et al. identified nucleobases that have not been identified in other meteorites.
Nucleo-what?
DNA is made up of letters called ‘nucleobases’, or i’ve referred to them as just ‘bases’ in this newsletter. Those letters are A, T, C and G, and they string together like beads on a string to make DNA. Importantly, the bases can be divided into two categories based on structural similarities: A and G, aka adenine and guanine, are called purine bases, and C and T, aka cytosine and thymine, are called the pyrimidine bases.
Ok got it. What did they find?
Historically, scientists have detected plenty of purine nucleobases (G and A) in meteorites. This study, however, identified various pyrimidine nucleobases as well- yes C and T, but also some of their structural counterparts such as isocytosine, imidazole-4-carboxylic acid, and 6-methyluracil. Most of these pyrimidine bases had not been detected in meteorites before.
What’s the takeaway?
This study begins to give us a better understanding of not only the distributions of organic material in meteorites, but also their formation pathways.
For example, the fact that pyrimidine bases haven’t been detected before, combined with the fact that the levels detected in these meteorites were very low, tells us that the nucleobases that make up our human DNA don’t necessarily fare well in extraterrestrial environments. It also may suggest that the formation of pyrimidines as we understand them (this would be the addition of side chains such as methyl and amino groups) may not be the dominant pathway we thought it was.
The really big picture here? This is yet another small piece of evidence we have gathered to answer the question: ‘How did life begin’? Understanding the commonalities between how our bodies are structured and how our Earth was formed by various meteorites and dust may help us understand the beginning of life as we know it.
Did the meteorites bring DNA and other genetic properties to Earth? TBD.
New treatment approved for Alzheimer’s disease
Pharmaceutical companies Eisai and Biogen led the development and testing of the new Alzheimer’s drug, Leqembi.
Amazing! Tell me more.
It is! Leqembi’s accelerated FDA approval was based on Phase 2 trial data, which showed that patients receiving the drug declined more slowly than those that received a placebo over 18 months. The patients receiving Leqembi declined by 1.21 points on an 18-point cognitive scale that assesses functions like memory and problem-solving, while patients receiving a placebo declined by 1.66 points. That amounts to a less than half a point, 0.45, or, a 27 percent slower decline. The Leqembi patients also declined more slowly on measures of cognition and daily function.
Of note, the drug should be used only for patients in early and mild stages of Alzheimer’s disease, like the patients in the clinical trials of the drug. This covers roughly 1.5 million people with Alzheimer’s in the U.S.
How does it work?
The drug works by attacking a buildup of the protein amyloid- this protein build-up is a hallmark sign of Alzheimer’s disease. Because of that, it should only be used to treat patients that have been shown to have a buildup of the protein amyloid on brain imaging.
That’s great, is there anything negative here?
There are potential side effects. Side effects include brain swelling and brain bleeding. For some not-quite-understood reason, patients with a genetic mutation (learn more about that in this post) that increases the risk of developing Alzheimer’s are at greater risk of brain swelling. In order to avoid these side effects, Leqembi’s label includes cautionary language about taking blood thinners while on the treatment.
What’s the takeaway?
Although there is skepticism out there about how much of a noticeable benefit this has, the prospect of a treatment for Alzheimer’s is exciting.
Since so far Leqembi has gotten ‘accelerated’ approval, the drug will need to go through another clinical trial before full approval. However, so far, all evidence points to a speedy full approval after Phase 3 trial data is out. If things go well, Leqembi could be on the market soon.
The utility of polygenic risk scores in predicting gestational diabetes
Researchers from McMaster University in Canada and Bradford Royal Infirmary in the UK analyzed more than 5,200 individuals from the pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies to evaluate the efficacy of combining polygenic risk scores with family history in predicting the onset of gestational diabetes.
What is a polygenic risk score?
A polygenic risk score (PRS) is a number, or a ‘score’ that estimates an individual’s risk for a certain condition. They are used in conditions that are caused by changes in many genes, often coupled with environmental factors.
How are they determined?
Let’s use gestational diabetes as an example, because that is the health outcome studied in this article. Scientists created PRSs for gestational diabetes by comparing the DNA of patients with and without gestational diabetes to determine a ‘collection of genes’ that have more rare variation in the individuals with gestational diabetes that are not there in the individuals without gestational diabetes. Then, they can say if you have these ‘X’ number of genes, your PRS for gestational diabetes is increased.
What did they find?
The researchers did, in fact, find that as PRS increased, the rate of gestational diabetes increased. This association was independent of maternal age, body-mass index, parental history of diabetes, and maternal birth country.
What's the takeaway?
Although the researchers saw a strong association between PRS value and gestational diabetes, they ultimately decided that the added benefit of adding PRS was not great enough to justify implementing PRS routinely in pregnancy. In other words, the association is there, but the accuracy is not. If implemented in clinic, there would still be a high chance of false positive risk based on PRS.
I’ve written about the utility of PRS to predict multiple medical conditions at this point; the different PRS having various degrees of utility in different conditions. It would be pretty amazing to be able to use a PRS (which is calculated from only a blood sample, by the way) to identify risks for common conditions, and especially for actionable conditions like gestational diabetes, where one can take preventive measures and increase screening. It is endlessly interesting to see how these predictions improve over time, changing the future of preventive health.