Cheers!

This is High on Health, your weekly bulletin on the pulse of health innovation, seamlessly intertwining the latest breakthroughs with timeless health wisdom.

As I checked the calendar this week, I realized only five weeks are left until Christmas, which means the holiday season is almost upon us! 😳🎄

It feels like it came by quickly, and I must admit I was unprepared for it. The remaining weeks before the break are just not enough to do all the things I agreed to do (looking at my wife), all the things that need to get done (sorry, everyone), and all the things that I want to do (easy there, big dog). 🤪 😱

I eagerly look forward to the holiday break; it is the only time everyone truly relaxes and takes a break. The level of inactivity during the break is even more than that of the summer break. 😴 😶‍🌫️

The lowlight of the week: our washing machine broke—a reputable German brand. She just turned three years old. This is a huge setback for us as a family of five, and the laundry is piling up everywhere. Moreover, adding my post-running clothes to the mix gives it an overpowering headnote of old sweat. 😮‍💨 🙃

A service technician was called to look into the issue. After examining it, the technician stated that the problem appeared to be serious (technician code for “expensive”) and that he needed to order replacement parts (more code meaning “expensive”). Additionally, the technician mentioned that he couldn't do the repair alone and would need to bring another technician (ultimate code for “really expensive”). It's important to note that the warranty for the machine is only valid for two years… 😩 👨‍🔧

This too shall pass. Just another growth opportunity 🥹

I hope y’all had a great week and are well-prepared for the final spurt of the year!

Take care!

Andre 🤔💡👨‍⚕️

The Scientist Who Saved the World

Next Steps for mRNA Vaccines and Therapeutics

The end of peanut allergies?

Messenger RNA technology

Do you remember when we all became mRNA experts in a matter of days in 2020? During the COVID-19 pandemic, the technology gained widespread attention as people tried to understand how it works.

Two pioneers of mRNA vaccine development, Katalin Karikó and Drew Weissman, were jointly awarded the 2023 Nobel Prize in Physiology or Medicine for discovering nucleoside base modifications. These modifications enabled the development of effective mRNA vaccines against COVID-19. This recognition has put the spotlight back on mRNA technology once again.

My wife shared an article with me about allergies (see above). According to the article, UCLA scientists have developed a revolutionary nanoparticle that can carry mRNA directly to liver cells. This approach trains the immune system to tolerate peanut protein, which could potentially help alleviate allergies. In their mice studies, this innovative method has yielded positive outcomes, significantly reducing severe allergy symptoms.

A brief history

This was reason enough for me to look into the topic again and start with a brief recap of events leading up to the famous pandemic response.

• The history of mRNA research dates back to the 1980s when scientists at Harvard University, including Douglas A. Melton, Tom Maniatis, and Michael Green, synthesized RNA enzymes to create biologically active mRNA in the lab. This process is still used today and involves using synthetic mRNA to study gene function.

• In 1987, Robert W. Malone¹ discovered that mixing mRNA with fat droplets allows human cells and frog embryos to absorb mRNA, producing proteins. This discovery was a foundational step for mRNA-based vaccine development.

• In the 1990s, mRNA was tested as a treatment in rats and as influenza and cancer vaccines in mice. During the 2000s, research in mRNA treatments and vaccines expanded, but challenges such as mRNA's fragility and high production costs limited funding and progress.

• In 2005, Katalin Kariko and Drew Weissman modified synthetic mRNA to prevent immune system attacks, advancing mRNA vaccine research. This led to increased study of mRNA treatments and vaccines in the 2010s.

• The emergence of the SARS-CoV-2 virus in China in 2019 led to the COVID-19 pandemic, and the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) issued prevention and treatment guidelines.

• In 2020, COVID-19 vaccine clinical trials commenced, utilizing previous research on similar viruses. The US Food and Drug Administration (FDA) authorized mRNA COVID-19 vaccines from Pfizer-BioNTech and Moderna.

Katalin Kariko’s story has been shared in many inspiring profiles. It's a tale of persistence in the face of adversity and pushing the limits in a world that sometimes can be unfair. The following quote from the Glamour profile above perfectly captures her spirit:

… the woman who had bounced from department to department, with no tenure prospects and never earning over $60,000 a year, said with total confidence: “In the future, this lab will be a museum. Don’t touch it.”

Bold will hold.

Quo vadis mRNA

So, what does the future hold for this technology beyond vaccines against viruses? Let’s look at the potential of the technique with immense potential in fighting cancer, flu, HIV, and autoimmune conditions.

Cancer Treatment

• mRNA technology is being used to develop personalized cancer vaccines. Scientists analyze the DNA of a tumor to identify specific proteins on the cancer's surface and then develop mRNA instructions to produce these proteins. This triggers the immune system to target the cancer cells. Self-destruction mode. 🧪 🔫

• Early trials conducted by Moderna and Merck for melanoma have shown promising results. The combined mRNA vaccine and immunotherapy treatment significantly decreased death and relapse risk. 📈 👍

• Studies are ongoing for different types of cancers, including lung and hepatocellular carcinoma, to complement existing treatments like surgery for non-metastasized cancers.🤝 🔪 

Flu Vaccination:

• Researchers are developing a universal flu vaccine using mRNA technology. Studies in mice have shown protection against all known influenza virus subtypes, suggesting the potential for a comprehensive flu vaccine. No flu, no cry. 🇯🇲 

• Like COVID-19 vaccines, the goal is to protect the most severe stages of the flu, even if it doesn't outright prevent infection. 🤧 🫷

Other Viruses:

• Moderna is developing an mRNA vaccine for Respiratory Syncytial Virus (RSV), a major cause of bronchiolitis in young children. 🫁 🧒

• Trials are ongoing for vaccines against HIV and the Epstein-Barr virus, which has been linked to multiple sclerosis. The challenge lies in identifying the right antigens for effective vaccine formulation. 🦠 😥

Autoimmune Conditions:

• mRNA technology shows promise in treating autoimmune conditions like lupus or rheumatoid arthritis. 👩‍🦽👐

• Other research includes modifying immune cells using RNA to treat conditions like cardiac fibrosis. Initial studies in mice have been successful, with plans to extend this research to human trials.🫀✌️

• Scientists are exploring the possibility of curing genetic disorders like sickle cell anemia with a single RNA injection, demonstrating the broad potential of this technology in various medical fields. 🩸 💉

So, there is some hope for our son, who has severe allergies to dairy, eggs, several nuts, and sesame (→ that’s why my wife shared the above-mentioned article). Due to his allergies, we have had to get creative with cooking and monitoring the ingredients of everything. Sadly, there is a long list of treats that other kids enjoy, but he can't have. It would be a game changer if an actual treatment option were available for him instead of just avoidance. Not having to carry an emergency kit with an EpiPen at all times would also be a huge relief.

Challenges to overcome

Collaborative efforts in mRNA technology are crucial to realize its potential fully. However, understanding the intricacies of this field may be difficult if you're not well-versed in biotech or lack a related educational background. I have attempted to make the main challenges accessible.

High Manufacturing Cost and Complex Processes:

Personalized vaccine development for solid tumors involves complex and costly manufacturing processes. mRNA technology could simplify the current production process, but the current methods (e.g., in CAR-T cell manufacturing) are time-consuming, difficult to scale, and expensive. 💸

Targeting and Delivery:

Achieving balance in mRNA construct design is crucial for ensuring both stability and efficiency. Developing active and passive targeting methods is essential for directing therapies to specific organs or tissues, particularly for diseases that affect vital organs. Improving the nonviral delivery of gene editing components via mRNA technology can help reduce off-target effects and toxicity. ☠️

Cold Chain Elimination:

To enable more stable storage and transportation of mRNA vaccines at higher temperatures, lyophilization techniques are being developed. During and after the lyophilization process, the efficacy and stability of mRNA (and other components) must be maintained. 🥶

Intellectual Property Challenges:

The landscape of mRNA technology is controlled by very complex intellectual property (IP), particularly related to essential components like capping technologies and modified nucleosides. This may restrict access and require expensive licensing, which could challenge new companies and innovations in the field. Ultimately, IP considerations may hinder the development of new RNA-based therapies. ⚖️

mRNA technology - not the easiest of topics. I still wanted to try it as there are promising therapy options in the future, lots of innovation is happening, and it’s somewhat part of popular culture given the pandemic.

I hope you found value and some new information!

As always, I would love to get your thoughts and comments!

¹ He became somewhat of a tragic figure. Dr. Robert Malone claims (somewhat rightfully so) to have helped invent mRNA vaccines but is now spreading unfounded claims about the vaccines and the virus. The discredited claims have bolstered a movement of misinformation.

A review of 15 studies has revealed that both low and high-intensity aerobic exercises can significantly alleviate anxiety symptoms. Notably, high-intensity exercise showed a more profound effect in reducing anxiety compared to low-intensity workouts.

This benefit was observed across a spectrum of anxiety conditions, ranging from general anxiety to specific anxiety disorders. The study involved participants exercising about three times a week for durations ranging from 10 weeks to six months, with the positive effects persisting even after stopping the exercise.

The anti-anxiety impact of exercise might be linked to the production of lactate during high-intensity workouts, which contributes to the generation of neurotransmitters like norepinephrine and serotonin, known to influence anxiety levels.

Machete, Orin Swift Cellars 2019

Anamnesis

Dave Phinney, a highly sought-after Californian winemaker, adopts a playful approach, whether crafting wines or designing his famously notorious labels. He draws inspiration for his label creations from diverse influences, including works of renowned artists, graffiti, and hip-hop lyrics. His Machete wine, a fantastic Rhône blend, features twelve different labels, sparking a collector's interest. To collect all twelve labels, one simply needs to purchase a 12-bottle carton.

Examination

The wine presents a deep, opaque, purplish-red hue with a dense center and delicate ruby-red edges. Its intoxicating bouquet is filled with aromas of marinated plums, fresh sour cherry juice, and dark chocolate truffles. A second sniff reveals notes of licorice, Dominican tobacco, and blackcurrant jam. The palate impresses with a creamy texture and perfectly ripe tannins that provide excellent structure. The wine boasts a robust body complemented by a cocoa-like sweetness in its extract. The finish is aromatic and long-lasting, featuring flavors of blueberries, a noble hint of Arabica coffee, and a refined, subtly peppery minerality.

Diagnosis

One of the most sought-after wines in California is worth getting if you can find it. It's not cheap, but I remember first opening a bottle of this fancy wine. I bought it in New York and read a display label that said, "It's a strange thing hearing that you've caught people off guard. They aren't quite sure what they have in front of them; they turn away confused, turn back, and inspect it again— what is this?" I was sold on it and still love it to this day.

DISCLAIMER: None of this (such as text, graphics, images, and other materials) is medical or health advice. This newsletter is strictly for informational, educational, and entertaining purposes only. While I’m a medical doctor and a dentist by training, I’m not your doctor. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on High on Health! Please be careful and do your own research.