Welcome back to The Vitals Podcast; I’m your host, Chauncey, back yet again to digest and bring you the latest in medical news today. It is Monday, May 20, 2024, and I have even more innovations to dig through with you. As always, don’t forget to follow the podcast and share it with your friends to keep everyone you know updated on the latest medical breakthroughs.
Our first story comes from Elias Sayour and his team at the University of Florida, who are testing a vaccine that teaches the immune system to attack the deadliest and most aggressive form of brain cancer.
Glioblastoma is extremely aggressive and particularly deadly. How deadly? Here are some facts: of the recorded cancer cases that affect the central nervous system (that is your brain and spinal cord), 45.2% are glioblastomas. Only 5.6% of adults affected have survived for at least five years after diagnosis; the median survival time for adults is 15 months. Treatment for this type of cancer involves surgical removal, followed by radiotherapy and chemotherapy, but it often comes back. But Sayour and his team may have a solution.
Now, there is a lot to unpack on how this works, so please bear with me here, but it all revolves around something called mRNA. Most of us know what DNA is; the information in our cells that tell them what to do by building proteins. Well, the DNA itself doesn’t go around and interact with machinery in our cells, just as builders don’t carry around the original blueprints; they take a copy to the construction site. Similarly, your cells house and protect your DNA, copy it, and send that copy out to build proteins. This copy is called mRNA. Here’s a fun bit of trivia, the “m” in mRNA stands for “messenger”.
Well, just like human cells, viruses have genetic code in the form of RNA. When they infect a cell, the viral RNA mimics our cell’s mRNA, forcing the cell’s machinery to build more viral proteins and viral RNA, which are then assembled and released to infect more cells.
Let’s take a breath here; to recap, our cells copy DNA to build proteins, and this copy is called mRNA. Viruses, like measles for example, carry viral RNA, which code to build viral proteins instead. Now, simplifying things a bit, your immune system “discovers” these viral proteins on the viruses and rallies an immune response, but takes a bit of time and allows the infection to make you sick before dispelling the pathogen. Once you do get better, however, it’s really unlikely you’ll get sick with the same virus again because your immune system will, in a way, “remember” this virus.
Vaccines take advantage of this by introducing a small, specific bit of that viral RNA into your bloodstream; let’s say measles again. This viral RNA will code for the proteins normally on the outside of a measles virus, proteins that your immune system can “discover.” When it enters and hijacks a healthy cell, it does NOT kill the cell, and the cell only builds and releases these bits of “discoverable” viral proteins, which your immune system promptly “discovers.”
The difference here is that the viral proteins aren’t a full-fledged measles virus, which means they aren’t enough to infect you and make you sick, but are enough for your immune system to “remember” the measles virus. That’s what immunity is. That means when the real thing comes along, your immune system can react much, much quicker.
What does ANY of this have to do with cancer vaccines? Well, Sayour’s method of treatment is surgically removing some of the glioblastoma (remember, that’s a brain tumor) from their patient (let’s call him Bob), extracting mRNA from the tumor sample, packaging it like a virus, and injecting it into Bob’s bloodstream. Essentially, they use lipid nanoparticles (small fat particles) to wrap around the RNA, which then codes for “discoverable” proteins made by Bob’s cancer cells. Bob’s immune system discovers the proteins and rallies an immune response. The difference between THIS and a viral vaccine is that the threat — Bob’s cancer — is still in Bob’s body.
So in reacting to a fake virus injected into Bob’s bloodstream, Bob’s immune system will also attack Bob’s glioblastoma as well, and hopefully, kill it. This process is replicated with Jane, with Jane’s unique glioblastoma, leading to Jane’s unique vaccine, spurring on Jane’s unique immune response.
Sayour’s team already observed the efficacy of this through animal clinical trials using 10 pet dogs that had glioblastomas (of course, at their owner’s consent). Normally, without treatment, their median survival would be 30-60 days. With this form of mRNA vaccination, the median survival was 4.5 months.
Using a group of four adult patients with glioblastomas, they did the same thing, and while it is too early to tell the results of this vaccination in humans, Sayour notes that, “In less than 48 hours, we could see these tumors shifting from what we refer to as ‘cold’—very few immune cells, very silenced immune response—to ‘hot,’ very active immune response.” If this is successful, the next step is moving to human clinical trials with more adults and children to confirm a correct dosage, and then to continue trials with pediatric patients.
This new, promising vaccination, if it’s safely tested in trials, could save a multitude of lives. Better yet, the potential this concept has to be replicated with other cancers (like lung cancer, the deadliest cancer in the US) brings us hope for what’s in store for humanity in the future.
RNA aggregates harness the danger response for potent cancer immunotherapy – ScienceDirect (Original Study)
What are mRNA vaccines and how do they work?: MedlinePlus Genetics
mRNA vaccine tackles deadly brain cancer in human trial (newatlas.com)
New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumor – UF Health
Our second story comes from Dr. Bryan Roth, the director of the NIMH Psychoactive Drug Screening Program at the University of North Carolina School of Medicine, who is working with his team of colleagues at UCSF, Stanford, and Harvard to prove the effectiveness of an AI that can give you potential drugs to treat neuropsychiatric diseases.
AlphaFold2 is an AI system that can model protein structures, and in your brain, there are a LOT of proteins. For example, your neurons, the cells that send messages back and forth, have receptors to receive neurotransmitters; receptors are made of proteins. One type of receptor is called a ligand binding site; neurotransmitters bind to these sites, which (and I’m simplifying here) will have some type of effect. These sites are often the target for psychiatric drugs, which will also have some therapeutic effect.
Recent studies have doubted the accuracy of AlphaFold2 when modeling ligand binding sites. So, Dr. Roth and his team decided to put this to the test.
AlphaFold2 works by referencing a huge database of proteins and their structures, which it can then use in simulations as targets for molecular compounds (like new potential drugs). Scientists can observe the simulated effects, learn how the binding site works, and develop even more drug candidates.
The AI can do this in two ways: retrospectively, which means it tells you of a binding with a protein it already has plenty of information on, or prospectively, which means it receives a completely new protein to assess and test against drug compounds. This study examined AlphaFold2’s prospective abilities.
The researchers first fed the AI the structures of sigma-2 and 5-HT2A, two receptors important in cell communication. Complications involving these receptors have been implicated in neuropsychiatric conditions such as Alzheimer’s disease and schizophrenia.
Researchers determined that the proportion of compounds that actually altered protein activity for each of the models were around 50% for the sigma-2 receptor and 20% for the 5-HT2A receptor. For reference, a result greater than 5% is exceptional. What’s more, out of the hundreds of millions of potential combinations using the sigma-2 receptor, 54% of the drug-protein interactions modeled by the AI were successfully activated, similar to the 51% success rate of the control model.
AI is becoming a part of plenty of fields, and medicine seems to be one of them. With this promising data, AlphaFold2 and other AI programs like it could be honed and perfected to help develop better and better treatments for us non-robots around the world.
AlphaFold2 structures guide prospective ligand discovery | Science (Original Study)
Researchers wrestle with accuracy of AI technology used to create new drug candidates | ScienceDaily
Now, it is time for THE VITALS, where I go in-depth on what you need to know about topics of your choice. If you’d like your question to be answered, drop it down in the Q&A, and you may see it in a future episode.
This episode’s vital question comes from Pete, who asks, “How are we dealing with COVID in 2024?”
Great question, Pete. We all know about the COVID-19 pandemic that lasted from 2020 – 2023. This disease has taken the lives of approximately seven million people worldwide, 1.2 million of which were in the United States according to WHO. It shut down schools, childcare, and businesses, and cost the US economy an estimated $14 trillion in net economic output, according to USC.
Vaccines made by Pfizer, Moderna, and AstraZeneca all rolled out on Emergency Use Approval (EUA) in December of 2020, and Johnson & Johnson rolled out their vaccine in February of the next year, and in both clinical trials and the real world, proved to be effective against COVID-19. According to WHO, as of the last day in 2023, 70% of the United States population is fully vaccinated, and 82% of Americans have at least one dose of a COVID-19 vaccine. So why do we still have COVID-19 going around?
I’m sure you’ve heard what variants are. There’s the Alpha variant, and the Delta Variant, and the Omicron variant, and so on, but what is a variant, and how do they occur?
Remember when we were talking about viruses having genetic code? Well, when it makes more copies of itself, it sometimes makes mistakes. Actually, it makes a lot of mistakes. When they happen in the virus’s genetic code, that’s called a mutation. When a virus mutates enough (when the “discoverable” proteins are different enough), the weapons in your immune system do not recognize it anymore. Essentially, the immune system treats it like a whole new virus, starting the immunity process again. This is what variants are; viruses mutated from the original virus.
Many viruses mutate, but some are more prone to mutate than others. For example, Rhinoviruses (the viruses that cause the common cold) and Influenza viruses mutate often, which is why there are so many variants that can get you sick. Viruses that cause smallpox, chickenpox, and measles all mutate a lot less, which is why when you catch these infections, it’s unlikely you catch them again.
COVID-19, in comparison, mutates a lot, hence the variants and subvariants of seemingly the same virus, and the many vaccinations and boosters to combat them.
Fun fact before we close, though; no matter the variant, thoroughly washing your hands with soap and water, and coughing or sneezing into your elbow will always prevent the spread of infection!
COVID-19 deaths | WHO COVID-19 dashboard
COVID-19 vaccines | WHO COVID-19 dashboard
That’s all for this week’s episode, so thank you for tuning in! Follow the podcast and share this episode with your friends! If you’d like your questions answered, remember to drop a response in the Q&A section of this video. Until next time, keep your vitals strong and your spirits high. This is your host Chauncey signing off. Take care and stay healthy, I’ll see you next week!
I will refresh the weary and satisfy the faint.
Jeremiah 31:25 NIV