I’ve been taking statins for more than 14 years. Finding the right pill was torturous because of the side effects I experienced. The first statin I was prescribed made me feel like someone was punching me in the kidneys. It took several weeks after I stopped taking the statin for the pain to go away. When I was given a second option, the pain in my lower back was more manageable but it wasn’t until a pharmacist suggested I take a CoQ10 supplement along with the statin, that I finally found relief. My cholesterol levels have been under control now for a long time.

My wife recently was prescribed a statin for high cholesterol. Her side effects have been more alarming and she has had the prescription changed and twice has gone off the daily pill taking.

My brother-in-law uses an alternative injectable medication to control his cholesterol levels. He couldn’t tolerate statins either.

So much for putting the stuff in drinking water.

Combatting high cholesterol, however, is vital because as a chronic condition, it can double your risk of having a heart attack or stroke.

A Promising Vaccine Could Replace Statins

Recently, I read about an American company working on a vaccine to treat high cholesterol. The company is Vaxxinity, Inc., and so far, in non-human primate studies, their product, VXX-401, is demonstrating good results in treating hypercholesterolemia (high cholesterol) and preventing atherosclerotic cardiovascular disease. The study results have recently been published in The Journal of Lipid Research. The company is now in Phase 1 clinical trials.

VXX-401 vaccine, when administered to cynomolgus monkeys, showed that it stimulated their immune systems to produce antibodies to target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), a natural protein associated with the production of cholesterol in the body. By blocking PCSK9, the vaccine lowered cholesterol levels in the blood.

Facts About Cholesterol

It is a waxy substance found in all cells in the body. It plays a significant role in the production of hormones, vitamin D, and bile acids. It comes in two forms: Low-Density Lipoprotein (LDL-C) and High-Density Lipoprotein (HDL).

The former, LDL-C, has been given the moniker “bad cholesterol” because when there is too much of it, it can build up on arterial walls where it can block blood flow and compromise the heart. Both cholesterols are produced in the liver and small intestine.

HDL, the “good cholesterol” controls LDL-C levels in the blood helping the body to get rid of too much.

High LDL-C levels can have a genetic component, but most often lifestyle, diet, and weight are the cause.

Vaccine Results So Far

VXX-401, so far, has demonstrated it reduces LDL-C levels on average by 44% in animal studies. It also appears to be well tolerated. Across three separate preclinical studies in cynomolgus monkeys, VXX-401 induced a strong and durable antibody response against PCSK9 and robust, sustained reduction of LDL-C over time. Prolonged exposure with VXX-401 resulted in an average of 44% LDL reduction. VXX-401 was well tolerated and did not induce any toxicity or pathology beyond mild injection site reactions. These results suggest that VXX-401 could be a safe and effective anti-PCSK9 immunotherapy.

VXX-401 was designed using Vaxxinity’s proprietary synthetic peptide vaccine platform Mei Mei Hu, Vaxxinity’s CEO, in a press release announcing the publication of the latest non-human primate results stated, “Despite multiple approved medications for LDL-C reduction, heart disease remains the number one killer in the world. A cholesterol vaccine like VXX-401 may provide a cost-effective and widely deployable solution that could potentially benefit hundreds of millions of people at risk. A well-tolerated intervention that people can start early in life, and remain on for many years, lowering the cholesterol ‘area under the curve,’ has the potential to help us win the fight against heart disease.”

Phase 1 of the clinical trial of VXX-401 is focused on determining the safety of its administration and how well it is tolerated in humans. We should see preliminary results by late summer.

Vaxxinity isn’t just looking at treating hypercholesterolemia. The company’s mission is to democratize healthcare through the pioneering of a new class of medicines aimed at disrupting existing treatments for several chronic diseases while reducing the cost to patients. The company is using its novel synthetic peptide immunotherapy vaccine candidates to treat Alzheimer’s, Parkinson’s, migraine, and COVID-19.

Periodically, cures for tinnitus appear in the media. They can be classified into four categories: sound therapy, behaviour therapy, medication, and surgery. The first two involve retraining the brain. By focusing on the sounds, some therapists believe you can learn to ignore them. Others believe that using cognitive-behaviour therapy can desensitize you to the sounds. Neither of these two have worked for me. I haven’t gone the medical or surgical route and don’t intend to.

Medical professionals who deal with tinnitus include audiologists and otolaryngologists. When you talk to them about the condition, most will admit that no treatment for tinnitus eliminates it in its entirety. Trying to measure the condition is nearly impossible with the advanced medical technologies we have today. Instead, hearing specialists only have a patient’s descriptions of the condition to use for treatment guidance.

In December of last year, I posted to this blog site an article on new research into the cause of tinnitus. I wrote about a technological cure called Lenire which had received US FDA approval. It featured 30-minute sessions which involved a tongue pulse stimulation device designed to retrain the brain to ignore the condition.

Lenire is an example of a medical device that uses bimodal neuromodulation which refers to a simultaneous or sequential application of two different neuromodulation techniques to target specific neural circuits in the brain and modulate or switch off the transmission of signals like the sounds experienced by those with tinnitus.

Bimodal neuromodulation today is being used with a combination of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) to treat Parkinson’s disease, a neuromuscular disorder. Another example being used to treat neurological disorders involves combining optogenetics and chemogenetics. Optogenetics uses a technique to genetically modify neurons to express light-sensitive proteins to precisely control neural activity related to light. Chemogenetics activates genetically engineered receptors to control neural activity. The combination is showing promising results in treating epilepsy, addiction, and depression.

An article in The Washington Post that appeared on January 19th of this year caught my attention and led me to revisit the subject. It described the latest bimodal neuromodulation treatments for tinnitus. One of them was Lenire which uses a combination of headphones playing a range of high and low sounds along with background noises while wearing a mouthpiece that sends electrical pulses to the tongue. In theory, the combination causes our brains to focus more on the high and low sounds rather than on the background tinnitus.

According to the Washington Post article, Lenire is one of three bimodal neuromodulation devices and treatments being hailed as game changers in tinnitus treatment. Neosensory’s Duo uses a haptic wristband to produce vibrations that get transmitted through the skin which when combined with synchronized sounds creates a similar treatment outcome. A third technology being developed at the University of Michigan delivers electrical pulses to the neck or jaw while the wearer listens to sounds through a headset.

These bimodal neuromodulation treatments are very different from anything offered to tinnitus sufferers. Studies reported in peer-reviewed journals, however, have used tiny sample sizes for tests. In the case of both Lenire and Duo, these studies have not used a placebo-control group as a means of comparison. Does that matter? As one tinnitus researcher described the Lenire and Duo results, the patients enrolled in these studies may have been experiencing a placebo effect, just being grateful for having been offered any kind of treatment. As one sufferer described tinnitus, “You get to the point where you’d give up your right arm to get rid of the noise.” I couldn’t concur more.

A 2022 study published in the Lancet used health statistics from 2019 to show that 7.7 million deaths globally that year were linked to 33 types of bacterial infections. The number was only second to ischemic heart disease as the cause of death in humans. The five leading bacteria include Staphylococcus aureus (SA), Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa accounting for almost 55% of the total.

The MIT researchers used AI to select and predict the best molecules for producing drug compounds that could work on killing SA. James Collins, Professor of Medical Engineering at the MIT Institute for Medical Engineering and Science, describes deep learning as “time-efficient, resource-efficient, and insightful.”

The results appear in the December 20, 2023 issue of Nature, and show that the deep-learning identified drug compounds kill methicillin-resistant SA. The researchers also report that they can see what the deep-learning AI is doing as it searches through millions of molecular combinations to find candidates that show good potency and very low toxicity when in contact with human cells to make them good antibiotic candidates.

SA causes skin infections, sepsis, a fatal bloodstream infection, and pneumonia in more than 80,000 people in the United States every year leading to 10,000 deaths. It is not the only targeted bacteria the MIT researchers are looking at through the lens of AI deep learning. Recently they identified a compound to treat the drug-resistant bacteria, Acinetobacter baumannii (AB) commonly found in hospitals.

Before the discovery of a potential drug compound to deal with SA, AI searches suffered from the “black box” effect. Black boxes don’t reveal how they draw their conclusions. But with SA research the deep-learning AI was wide open to see the connections and calculations the neural network was doing. The use of expanded datasets was key to training the AI and used 39,000 compounds and their chemical and molecular structures. Shuffling the atoms and bonds around also allowed the AI to discern in percentages the probabilities of antibacterial success.

A Monte Carlo algorithm was used. It relies on repeated random sampling to obtain numerical results and gets its name from the Monaco casino where it was first used to simulate roulette games. Monte Carlo works by generating large numbers of random samples to determine the probability of a desired output. The AI-deep learning used the algorithm to generate estimates of a molecule’s antimicrobial activity and predictions about which substructures of the molecule likely accounted for the activity. To predict human toxicity to identified compound candidates, the researchers trained three additional deep-learning models. The combination of these AIs provided a short list of desirable compounds that not only killed SA but also did no harm to humans.

Twelve million commercially available compounds were reviewed by the AI. It identified five class types exhibiting the right chemistry. A total of 280 were available for purchase off the shelf. These were tested with two showing considerable promise. Each showed in the laboratory that they could disrupt SA bacteria in infected mice by disrupting the electrochemical gradient across cellular membranes, critical to cell function. In exposure to human cells, there was no disruption.

The MIT results have been shared with Phare Bio, a nonprofit company that has participated in the project. The company and MIT will work on turning these promising compounds into a drug for clinical use. They will continue to work using AI deep learning to discover other candidates to fight drug-resistant bacteria. This should lead to new antibiotics to fight bacterial infections that no longer respond to the drugs we have in our current medical arsenal.

Before we tackle this subject it would be good to have a definition. What is Long COVID? It describes COVID-19 symptoms that persist beyond 12 weeks. The average gestation for COVID-19 with resolution of symptoms lasts up to 4 weeks. But when symptoms persist without any alternative explanation, the individual who has had COVID is deemed to be suffering from Long COVID.

From a study on population groups, the U.S. National Institute of Health (NIH) has come up with a list of 37 discrete COVID-19 symptoms that include post-exertional malaise (the worsening of symptoms after physical or mental activity), fatigue, brain fog, dizziness, gut symptoms, heart palpitations, sexual problems, change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements such as muscle twitching or jerking. Of these 12 have appeared to be persistent in individuals suffering from what we call Long COVID.

Why a nasal spray?

Because COVID-19 spreads through the air with its most common entry path through our airways. That’s the reason all of our testing to date has involved nasal swabs whether PCR or rapid detection. The epithelial cells in the lining of our noses is the place where the virus first lodges and incubate before finding its into the rest of our bodies. Our epithelial cells are most in peril from the initial viral onslaught and in terms of complications as it spreads. And epithelial cells line all of our organs including the lungs, and heart, and blood vessels. So an anti-COVID neutralizer used at the point of viral entry would be an efficient preventive. And a nose spray delivery system would make the application very simple.

So far, TriSb92 is working in animal model studies. It identifies an area on the spike protein common to all variants of the virus. Spraying into the nose prevents infections even a few hours after exposure. Developed at the University of Helsinki, the TriSb92 nasal spray can be stored at room temperature and remains potent for at least 18 months.

A press release from the University quotes Anna Mäkelä, a postdoctoral researcher in the Department of Virology. She is the lead author of the article published last week. She notes that targeting the “inhibitory effect of the TriSb92 molecule to a site of the coronavirus spike protein common to all variants of the virus makes it possible to effectively inhibit the ability of all known variants, Omicron included, to infect people.” She comments further noting that TriSb92 can prevent SARS, the coronavirus from the global epidemic of 2004. And she expresses confidence in the nasal spray treatment to protect humans from “entirely new coronaviruses that may threaten to cause pandemics.”

Kalle Saksela is a professor in the Department of Virology at the University. Mäkelä’s research has been supervised by Saksela who is working on a nasally administered coronavirus vacemphasizeh is expected to go into clinical trials this spring. Both Saksela and Mäkelä empahsize that the nasal spray is not a substitute for being vaccinimmune-compromised-19, but rather a preventive.

When TriSb92 psses human clinical trbeforewill offer immune compromised individuals vulnerable to the virus, with a preventive spray they can use before going to a social event. It also should prove helpful to people who have not found the vaccines as effective in preventing them from getting COVID-19. And should there of recurrences of COVID-19 or outbreaks of a new coronavirus, it could benefit the general population from egame-changerk.

So let’s hope that the human clinical trials are successful because TriSb92 sounds like a gamechanger for not just dealing with COVID-19 but also acting as a preventive against other coronaviruses.

In 2019, CRISPR started moving out of university research laboratories and into the world of medical clinical trials. In one case it was used to edit the DNA of T-cells by removing a gene and replacing it with one to attack sarcomas and multiple myelomas. A similar editing experiment replaced a gene in people suffering from beta-thalassemia, a genetic blood disorder. And in another trial, CRISPR-modified bone marrow stem cells were used to eliminate sickle cell anemia.

Among the Massachusetts Institute of Technology’s 10 technology breakthroughs in 2023, CRISPR made the list. Why? Because MIT sees CRISPR’s days in clinical trials around rare diseases coming to an end. The CRISPR of today, eleven years after it first came on the scene, is no longer just a slice-and-dice tool.

CRISPR Going Mainstream

CRISPR is being used by a company, Verve Therapeutics, today, to alter genetic code associated with high cholesterol that is treated using drugs called statins.

I take statins once a day because my cholesterol levels are slightly higher than normal. I remember when it was first prescribed, the doctor said the city should be putting statins in the drinking water just like fluoride because high cholesterol was a huge problem here in North America.

Cholesterol comes in two forms, one good, the other bad. Our bodies need good cholesterol because it is essential to cells. But too much of the bad kind can clog arteries and lead to strokes and heart attacks.

According to the U.S. Centers for Disease Control (CDC), more than half of American adults are on prescribed statins to reduce cholesterol levels. That number isn’t too far different in Canada. But there are problems with being on statins forever. Blood levels have to be checked periodically to ensure the doses are right and cholesterol levels are within the normal range. Statins also have side effects. For instance, when I first started on a statin I had horrific backaches. A pharmacist recommended I take a supplement, CoQ10, with the statin and the problem has never reoccurred.

Genetic Vaccines in Our Future

What Verve is offering instead of a statin, is the first genetic vaccine on the market, a one-time fix to permanently lower bad cholesterol levels. To understand how a genetic vaccine works here is a quick refresher on DNA. It is a complex molecule containing four nucleotides, also called nucleobases. They go by the names adenine, guanine, cytosine and thymine. These are the biological building blocks for life on Earth.

What Verve has done is use CRISPR to edit a single nucleobase within our DNA for PCSK9, a gene expressed in the liver. PCSK9 encodes a protein that regulates the amount of cholesterol in blood plasma. Delivered as a vaccine Verve has shown the treatment lowers blood cholesterol levels by as much as 70% and keeps it down permanently. Limited human testing has shown excellent results. Larger clinical trials are coming up.

From Verve’s curing high cholesterol to the use of CRISPR for genetic vaccines to cure other diseases is not too far in the future. A CRISPR-derived genetic vaccine could lead to a cure for diabetes, high blood pressure, and even Alzheimer’s.

CRISPR for the masses can be revolutionary. It has enormous ramifications for humanity with genetic vaccinations replacing many prescription drugs. And a genetic vaccination will only need to be administered once providing a permanent fix.

Those who see this as us playing God will likely react negatively to this medical breakthrough. I suspect the anti-vaxxers will be out with pitchforks in hand ready to march. And on the Internet conspiracy theorists will spread fear and misinformation about CRISPR and the evil intent of a medical cabal out to take over the world and turn us into zombies. For those who fit into these categories, the option of the prescription pills we have today will still remain.

In Part 1 we looked at innovations in Space and Energy in 2022. In Part 2 we tackle Health and the amazing number of breakthroughs.

And yes there will be Part 3 coming after the turn of the New Year.

Health

The #5 breakthrough on the list is the synthesizing of life without sperm or eggs. This year scientists from the Weizmann Institute of Science in Israel grew mouse embryos in a lab without the use of sperm, egg, or a womb. The scientists were able to do so by growing the mouse embryos inside a bioreactor made up of stem cells cultivated in a Petri dish. Using a mechanical uterus combined with a novel cocktail of stem cells—some of which were chemically programmed to overexpress genes that switched on the development of the placenta and yolk sac—the team produced embryos with gene expression patterns 95% similar to natural mouse embryos of the same age. The embryos developed normally, elongating on Day 3, folding their neural tubes and budding tails by Day 6, and developing beating hearts by Day 8. This marked the first time that scientists successfully managed to grow fully synthetic mouse embryos outside the womb.

What this means is scientists now have a better understanding of how some pregnancies fail and how to prevent this from happening. It marks a major leap forward in the ability to grow organs for transplant. It may even pave the way for new treatment strategies for diseases like cancer. Imagine, for instance, a patient with untreatable leukemia that needs a bone marrow transplant to survive. In the future, we may be able to biopsy skin cells from that patient, rewind those skin cells into stem cells and then put those into a bioreactor to produce a stockpile of bone marrow stem cells that can be given back to the patient. It means no more waiting for a donor match.

The #6 breakthrough is research leading to 100% remission for early-stage rectal cancer. A New England Journal of Medicine study this year revealed that using Dostarlimab, a monoclonal antibody and checkpoint inhibitor has produced complete remission in early-stage rectal cancer patients. Approved by the FDA in August 2021, Dostarlimab blocks tumours that inhibit the body’s immune system T cells. With approximately 45,000 patients annually diagnosed in the United States, and on the increase in younger adults with estimates by 2030, of a 124% rise in patients between ages 20 and 34, and 46% in patients between ages 35 and 49, using Dostarlimab could eliminate the need for surgery, radiation, and chemotherapy with immune memory preventing future cancer spread. It also represents an advance in the use of checkpoint inhibitors for other cancer treatments.

The #7 breakthrough is the development of vaccines for Malaria and all Influenza strains. In September, a novel Malaria vaccine developed at Oxford University has proven to be up to 80% effective in preventing the disease. And in December, a research team at George Washington University announced the development of two highly-effective mRNA vaccines that also reduced Malaria infection and transmission as well.

Then in November, an mRNA-based experimental Influenza vaccine-induced protection against all known influenza subtypes in an animal study. The University of Pennsylvania vaccine produced antibody responses for all 20 known strains of Influenza A and B in tests on mice and ferrets. The protection lasted for 4 months.

With nearly 90 countries and territories in areas at risk for Malaria, and the fact that the disease kills 627,000 people annually, the majority of them children younger than five years old, a vaccine that inhibits transmission represents a significant breakthrough.

Influenza, which provides an annual challenge for medicine, constantly evolves to evade immune responses. That’s why a vaccine that addresses all variants is exciting. Blunting the harm of Influenza will be a big win for public health.

The #8 breakthrough is the use of AI to predict all known protein structures. How proteins fold determines the way they work in our cells. Protein folding has been one of the grand challenges for computer modellers since the 1960s. This year an AI program, AlphaFold2, built by DeepMind, a Google company, has solved the 3D structures of roughly 200 million known proteins. This breakthrough has been followed by researchers from Meta announcing the use of an AI tool that has allowed them to predict the structures of roughly 617 million proteins in bacteria, viruses, and other microorganisms yet to be fully characterized. The Meta AI took just two weeks to produce these results. And Meta (formerly Facebook) is making a free API (application program interface) available to all to use it.

Right now DeepMind’s AlphaFold2 is being used for research on COVID-19, cancer, and antibiotic resistance. DeepMind has set up a public database for protein structures predicted by AlphaFold2 which currently has approximately 1 million entries with 100 million more to be added in the next year. And Meta’s database, the ESM Metagenomic Atlas, should produce the protein structures of millions more.

Almost everything in our bodies is determined by protein interactions. Understanding their structure and function, therefore, is critical in dealing with diseases and developing treatments. With these two tools, our 3D protein structure prediction capacity will grow astronomically helping scientists to pinpoint the root causes of diseases and develop effective drugs for their treatment.

The #9 breakthrough involves the revival of organs in dead pigs. Researchers at Yale University earlier this year successfully revived cells in the hearts, livers, kidneys, and brains of pigs that had been declared dead for one hour in a laboratory. Revival was accomplished using a device similar to a heart-lung machine. A  unique solution, OrganEx, was circulated in the bodies of the deceased pigs. This caused the pigs’ hearts to start beating and pumping it throughout their bodies. While the pigs were dead, their organs became functional again. What this means for organ transplantation is significant because every year in the U.S., 100,000 people are on waiting lists for organ transplants. Each day, 17 people die while waiting and a new name is added to the list every 9 minutes.

In the short term, scientists hope that OrganEx could help doctors preserve the organs of the recently deceased for transplants. This would provide doctors with viable organs from bodies long after death has occurred. The technology can also be used to limit damage from heart attacks and strokes with longer-term implications for reversing sudden death.

The #10 breakthrough is happening in human genome sequencing. Illumina, a genomics company, this year unveiled the NovaSeqX genome sequencers These machines represent a breakthrough in sequencing cost, at $200 compared to $3 billion the first time it was done, $100 million for the second, $10,000 a decade ago and $600 today. In addition, the machines produce results twice as fast as current sequencers. At about $1 million per machine, each can generate 20,000 whole genome sequences per year.

What genome sequencing allows doctors to do is detect cancers early using simple blood tests. It makes it possible to develop genetically-targeted drugs. And it is proving to be useful in diagnosing rare diseases and developing new COVID-19 vaccines.

The cost has always been a problem with this technology. But with Illumina’s new machine genomic medicine can enter the mainstream and create a future where every child born is automatically sequenced to anticipate and plan for the treatment of revealed childhood diseases, and patients when admitted to hospital, get sequenced to help facilitate treatment.

The #11 breakthrough advance in cancer treatment combines the use of mRNA vaccines and immunotherapy. Moderna’s mRNA-4157/V940 and Merck’s Keytruda immunotherapy treatment, in combination, have been shown to successfully cure melanoma, the deadliest skin cancer. In a Phase 2 clinical trial, the combination of the two reduced the risk of recurrence and of death by 44% compared to treatment using Keytruda immunotherapy alone.

If you didn’t know it, cancer is a group of more than 200 diseases affecting tens of millions annually. In 2022 in the U.S., nearly 2 million new cancer cases will have been diagnosed. Globally, almost 10 million cancer-related deaths occur each year.

The Moderna and Merck study demonstrates for the first time the efficacy of mRNA-based cancer treatments in a clinical trial. The encouraging results are paving the way for a Phase 3 trial, and the potential approval in the near future of the first mRNA cancer vaccine. The upside of mRNA vaccine technology is it can be used to develop treatments for many other cancers.

We’ll continue this list of amazing scientific and technological breakthroughs in Part 3 when we look at advances and breakthroughs in the fields of Food and Robotics. So stay tuned.

In his mid-80s, my father-in-law (seen in the above picture at an earlier time in his life) suddenly found walks from his midtown home to his jewellery store in the heart of downtown Toronto, were suddenly getting much harder. He described what he was experiencing as walking wearing concrete shoes. He would become breathless at times. This was a man who cycled 20 kilometres almost every weekend. Referred to a cardiologist, he learned he had a genetic disorder, hypertrophic cardiomyopathy, and that its appearance in his 80s was indeed rare.

Hypertrophic cardiomyopathy is one of those heart ailments with a genetic link. It causes the heart muscle to thicken losing its flexibility as a pumping chamber. As the heart wall, particularly the septum which separates the left and right ventricles, thickens it begins to impede blood flow through the aortic valve to the rest of the body.

Although hypertrophic cardiomyopathy can happen at any age, it is rare to begin expressing symptoms in someone as late as it did with my father-in-law. Most of those who get it have a family history of the disease. The odds of inheriting the genes are 50/50. That’s why my wife is followed by a cardiologist regularly.

At the time my father-in-law was given his diagnosis he was offered two options. One involved an operation to ablate, that is burn away a part of the thickening walls, to restore flexibility. The second was a pacemaker. He chose the latter.

Cardiomyopathies occur in about 1 in every 250 people. In the U.S. approximately 1.5 million are affected. Many are unaware. It appears in all life stages. In addition to hypertrophic there are other cardiomyopathies. These include:

• restrictive cardiomyopathy with the heart muscle becoming more rigid and usually associated with another heart disease present
• arrhythmogenic right ventricular dysplasia, a version of cardiomyopathy that damages the right side of the heart.

People with cardiomyopathy more often find their lives shortened although not in the case of my wife’s family. My father-in-law died at age 97. His father had it but lived to age 92. And his sister also was diagnosed with it and died at age 102. It looks like they had other genes that were working in their favour.

Cardiomyopathies are life-threatening. They cause arrhythmias and can lead to a stroke, heart failure or even a heart attack. When young people get diagnosed with hypertrophic cardiomyopathy the option today is a heart transplant or a very shortened lifespan. With arrhythmogenic right ventricular dysplasia in young people, defibrillators can be implanted to stop the arrhythmia and a heart transplant is the only other option.

A Cure on the Way for Genetic Heart Conditions

CureHeart was formed by a group of researchers from a global community that includes the University of Oxford, Harvard, the Broad Institute, Duke, Share, Wave Life Sciences, Myokardia, and Cardiomyopathy UK, a heart muscle charity. Their work on gene therapy for cardiomyopathy recently won them the British Heart Foundation’s Big Beat Challenge, a contest that involved 75 entries from around the world competing for a £30 million grand prize.

The CureHeart team uses a technique called base and prime editing to suppress and eliminate faulty genes linked to inherited heart muscle diseases. They have identified specific genes that work alone or in combination with others responsible for genetically inherited heart conditions like cardiomyopathies. Mice studies are showing that in some cases a faulty gene can be repaired or switched off. But cardiomyopathies can involve a cascade of gene interactions following a specific sequence which means treating them in isolation isn’t sufficient. So CureHeart is developing a way to switch off faulty genes, edit and correct them, and do it in correct sequence.

The plan is to deliver a cure through a vaccine which can be administered like any other, a shot in the arm, or can be introduced through the chest wall directly into the heart muscle itself. The end product would be offered to family members with a history of genetically-associated cardiovascular disease.

As a parent of a child born with congenital heart disease, the CureHeart project represents an exciting development for coming generations. The team notes that what can work for cardiomyopathy could prove to be useful for curing other inheritable cardiovascular diseases. And it doesn’t have to stop at the heart considering the numerous other gene-associated diseases that humanity faces. If successful, vaccine-delivered cures like these could become standard treatment in reversing bad genes. This medical advance will be a remarkable achievement.

The latest mutation of COVID-19 has been given the Greek letter Omicron (we skipped Nu and Xi to minimize Mu confusion and the obvious association of the latter name with China’s current leader). Omicron was genetically mapped first in South Africa. It differs from the current dominating variant, Delta, because it has a large number of new mutation characteristics.

The scientific name for Omicron is COVID-Sars2-B.1.1.529. Its spike protein has 30 new variations differentiating it from Delta and other previous versions of the virus. Some of these differences can be found in Alpha and Delta and what has raised concerns is that the differences are linked to increased infectivity and antibody avoidance characteristics for the virus. It goes beyond antibody avoidance because initial study suggests this evolved variant can dodge our T attack cells that are a critical component of the body’s immune response.

COVID-19 has four different proteins of which the spike is one. The spike in the diagram below is designated S. The rest are N, HE, and M.

The latest research shows our natural immune system reacts to all four proteins, but less to the S than the N, the latter which is found inside the virus capsule wrapping around its RNA core. The problem is that the S is the vehicle of entry and the N is only seen after the horses have left the stable and seeded other healthy cells with more viruses.

Knowing that the N is more visible to our immune system than the other proteins should give vaccine developers a brand new tool with which to work. By adding N-protein antibodies to new vaccines we can enhance them and the body’s immune response. The added benefit to such a strategy would be that, with N common to many other coronaviruses, unlike the spike protein, it would make a new generation of vaccines truly multivalent.

Multivalent vaccines deliver multiple antibodies and can provide lifetime protection for a range of viral infections. These vaccines combine treatments for several diseases through a single course of jabs. Think measles, mumps, and rubella, the multivalent vaccine most commonly used today and you get the idea.

In this case, a new multivalent vaccine would recognize all COVID-19 variants, and all the other coronaviruses responsible for illness in humans. Just in case you didn’t know it, we have been dealing with coronaviruses for a long time. The U.S. Centres for Disease Control and Prevention lists four responsible for upper-respiratory-tract infections similar to the common cold. We have learned to live with 229E, NL63, OC43, and HKU1, all airborne, close-contact, or surface transmitted viruses that are prevalent every fall and winter. Today we treat these infections with home remedies. A multivalent mRNA vaccine that tackles COVID-19 would also eliminate these other seasonal coronavirus infections. Better still, a multivalent or multi-disease mRNA vaccine could target more than just coronaviruses. A new lexicon of terminology describes these future treatments which include:

• Multivalent/polyvalent vector vaccines – combining different strains of one pathogen, for example, COVID-19 into a single vaccine to eliminate that disease in all its variants exclusively.
• Multidisease/multi pathogen vector vaccines – combining the treatment of two or more pathogens through the administration of a single vaccine to eliminate several diseases.

How they work is well illustrated below.

So in the next decade could we be seeing new candidate vaccines not only to tackle COVID-19, but HIV, malaria, and other viral infections? Biopharmaceutical companies and researchers in universities and hospitals around the world are working to make this a reality.

According to the science of late, age as a limit seems to be off the table. Researchers are discovering that the ageing process has a lot to do with how our immune system operates. If in overdrive it causes a hyper-inflammatory response which in time leads to diseases and conditions associated with old age: strokes, heart disease, cancer, and neurodegenerative conditions such as Alzheimer’s. So the thinking goes, if keep our immune systems calm, human life can be extended well beyond today’s upper limits which appear currently to be around 120?

Parabiosis Research Leads to the Evolution of TPE Therapy

Back in 2017, I remember reading a paper on a phenomenon known as parabiosis, in which the authors used the words “fountain of youth” in describing the outcome of their research. It was the first time I had seen this term which is a laboratory technique that links the physiology of two living organisms for experimental purposes.

A laboratory at UC Berkeley, headed up by Irina Conboy in the Department of Biological Sciences, has been using parabiosis in its research. In 2005 it published the results of an experiment involving two mice. Conboy studies rejuvenation of tissue maintenance and repair, the role that stem cells play, directed organogenesis (the development of our body tissues and organs from the embryonic stage to birth and beyond) and making CRISPR (the gene slicing and dicing tool) a therapeutic reality.

In her mouse experiment, the circulatory systems of two were enjoined producing some very interesting observations. One was a young mouse. The other, old. Within five weeks, the older one began exhibiting more youthful characteristics.

What were these? In examining stem cell activity, they were seen to be actively dividing and helping to regenerate muscle mass and liver function. In other words, the exposure to the young mouse’s blood was causing the older mouse to appear to be getting younger.

The acronym TPE stands for Therapeutic Plasma Exchange, a procedure involving the passing of a person’s blood through an apheresis machine, a device which receives blood removed from a patient or donor’s body and separates it into its various components: plasma, platelets, white blood cells and red blood cells. With TPE treatment the red blood cells are retained and fresh plasma is infused into the recipient’s blood.  In addition to the plasma, albumin and immunoglobulin can be administered. The results of TPE therapy have been excellent for patients suffering from a number of medical neurological conditions such as Guillain-Barre Syndrome, and Myasthenia Gravis. But it also has application to many other diseases.

TPE research continues to evolve new plasma exchange “cocktails.” Combinations include saline, albumin, immunoglobulin and other solutions that when infused into patients produce regenerative results.

One study looked at treating Alzheimer’s Disease. It goes by the acronym AMBAR which stands for Alzheimer’s Management by Albumin Replacement. It involved 490 patients and was described in a 2020 paper published in Frontiers in Neurology. The TPE used was a cocktail of plasma, albumin, and immunoglobulin infused into some patients with others receiving a placebo. The study was looking at if the TPE cocktail could inhibit cognitive decline.

Applying the ADCS-ADL (Alzheimer’s Disease Cooperative Study – Activities of Daily Living) a test composed of 23 daily functions (i.e., dressing, washing dishes, reading, cooking, etc.) the researchers compared patients’ functional and cognitive abilities before and after applying the cocktail to measure the level of disease progression.

The graph below shows the comparative results between TPE-treated patients and the placebo group with neurodegeneration rates lessened by 66% in the former compared to the latter. This is encouraging and a sign that TPE as a regenerative therapy has considerable promise.

So what does this all mean when it comes to ageing? Clearly, TPE therapy could be a game-changer when addressing natural ageing processes and diseases of the aged. In its reversing of the inflammatory effect of our body’s immune systems, it can allow for regenerative processes to continue to function normally well beyond 80, 90 or 100 years, buying us extra time.

What we choose to do with the gift of our increased longevity will be up to each of us. In an Onion article, I read today, God is complaining that he never has had the time to learn Spanish. With all the time he supposedly has, wow, what an excuse.

My regret during this pandemic is that I didn’t do what I promised myself at the outset after the lockdowns and before getting COVID. I wanted to learn how to play the guitar. Instead, as the days passed, and after coming out of the brain fog of COVID, two operations and three cancer scares, I did jigsaw puzzles instead. It is only in the past few months that I have seen the fog lift and have started writing this blog regularly again.

But now, if I get a TPE infusion, maybe mastering the guitar is in my extended future. I can even throw in Spanish as well. So there, God.