Health breakthroughs of 2022 that should have made bigger news
As the world has attempted to move on from COVID-19 in 2022, attention has returned to other areas of health and biotech with major regulatory approvals such as the Alzheimer's drug lecanemab – which can slow the destruction of brain cells in the early stages of the disease – being hailed by some as momentous breakthroughs.
This has been a year where psychedelic medicines have gained the attention of mainstream researchers with a groundbreaking clinical trial showing that psilocybin treatment can help relieve some of the symptoms of major depressive disorder. And with messenger RNA (mRNA) technology still very much capturing the imagination, the readouts of cancer vaccine trials have made headlines around the world.
But at the same time there have been vital advances which will likely go on to change medicine, and yet have slipped beneath the radar. I asked nine forward-thinking experts on health and biotech about the most important, but underappreciated, breakthrough of 2022.
Their descriptions, below, were lightly edited by Leaps.org for style and format.
New drug targets for Alzheimer’s disease
Professor Julie Williams, Director, Dementia Research Institute, Cardiff University
Genetics has changed our view of Alzheimer’s disease in the last five to six years. The beta amyloid hypothesis has dominated Alzheimer’s research for a long time, but there are multiple components to this complex disease, of which getting rid of amyloid plaques is one, but it is not the whole story. In April 2022, Nature published a paper which is the culmination of a decade’s worth of work - groups all over the world working together to identify 75 genes associated with risk of developing Alzheimer’s. This provides us with a roadmap for understanding the disease mechanisms.
For example, it is showing that there is something different about the immune systems of people who develop Alzheimer’s disease. There is something different about the way they process lipids in the brain, and very specific processes of how things travel through cells called endocytosis. When it comes to immunity, it indicates that the complement system is affecting whether synapses, which are the connections between neurons, get eliminated or not. In Alzheimer’s this process is more severe, so patients are losing more synapses, and this is correlated with cognition.
The genetics also implicates very specific tissues like microglia, which are the housekeepers in the brain. One of their functions is to clear away beta amyloid, but they also prune and nibble away at parts of the brain that are indicated to be diseased. If you have these risk genes, it seems that you are likely to prune more tissue, which may be part of the cell death and neurodegeneration that we observe in Alzheimer’s patients.
Genetics is telling us that we need to be looking at multiple causes of this complex disease, and we are doing that now. It is showing us that there are a number of different processes which combine to push patients into a disease state which results in the death of connections between nerve cells. These findings around the complement system and other immune-related mechanisms are very interesting as there are already drugs which are available for other diseases which could be repurposed in clinical trials. So it is really a turning point for us in the Alzheimer’s disease field.
Preventing Pandemics with Organ-Tissue Equivalents
Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine
COVID-19 has shown us that we need to be better prepared ahead of future pandemics and have systems in place where we can quickly catalogue a new virus and have an idea of which treatment agents would work best against it.
At Wake Forest Institute, our scientists have developed what we call organ-tissue equivalents. These are miniature tissues and organs, created using the same regenerative medicine technologies which we have been using to create tissues for patients. For example, if we are making a miniature liver, we will recreate this structure using the six different cell types you find in the liver, in the right proportions, and then the right extracellular matrix which holds the structure together. You're trying to replicate all the characteristics of the liver, but just in a miniature format.
We can now put these organ-tissue equivalents in a chip-like device, where we can expose them to different types of viral infections, and start to get a realistic idea of how the human body reacts to these viruses. We can use artificial intelligence and machine learning to map the pathways of the body’s response. This will allow us to catalogue known viruses far more effectively, and begin storing information on them.
Powering Deep Brain Stimulators with Breath
Islam Mosa, Co-Founder and CTO of VoltXon
Deep brain stimulation (DBS) devices are becoming increasingly common with 150,000 new devices being implanted every year for people with Parkinson’s disease, but also psychiatric conditions such as treatment-resistant depression and obsessive-compulsive disorders. But one of the biggest limitations is the power source – I call DBS devices energy monsters. While cardiac pacemakers use similar technology, their batteries last seven to ten years, but DBS batteries need changing every two to three years. This is because they are generating between 60-180 pulses per second.
Replacing the batteries requires surgery which costs a lot of money, and with every repeat operation comes a risk of infection, plus there is a lot of anxiety on behalf of the patient that the battery is running out.
My colleagues at the University of Connecticut and I, have developed a new way of charging these devices using the person’s own breathing movements, which would mean that the batteries never need to be changed. As the patient breathes in and out, their chest wall presses on a thin electric generator, which converts that movement into static electricity, charging a supercapacitor. This discharges the electricity required to power the DBS device and send the necessary pulses to the brain.
So far it has only been tested in a simulated pig, using a pig lung connected to a pump, but there are plans now to test it in a real animal, and then progress to clinical trials.
Smartwatches for Disease Detection
Jessilyn Dunn, Assistant Professor in Duke Biomedical Engineering
A group of researchers recently showed that digital biomarkers of infection can reveal when someone is sick, often before they feel sick. The team, which included Duke biomedical engineers, used information from smartwatches to detect Covid-19 cases five to 10 days earlier than diagnostic tests. Smartwatch data included aspects of heart rate, sleep quality and physical activity. Based on this data, we developed an algorithm to decide which people have the most need to take the diagnostic tests. With this approach, the percent of tests that come back positive are about four- to six-times higher, depending on which factors we monitor through the watches.
Our study was one of several showing the value of digital biomarkers, rather than a single blockbuster paper. With so many new ideas and technologies coming out around Covid, it’s hard to be that signal through the noise. More studies are needed, but this line of research is important because, rather than treat everyone as equally likely to have an infectious disease, we can use prior knowledge from smartwatches. With monkeypox, for example, you've got many more people who need to be tested than you have tests available. Information from the smartwatches enables you to improve how you allocate those tests.
Smartwatch data could also be applied to chronic diseases. For viruses, we’re looking for information about anomalies – a big change point in people’s health. For chronic diseases, it’s more like a slow, steady change. Our research lays the groundwork for the signals coming from smartwatches to be useful in a health setting, and now it’s up to us to detect more of these chronic cases. We want to go from the idea that we have this single change point, like a heart attack or stroke, and focus on the part before that, to see if we can detect it.
A Vaccine For RSV
Norbert Pardi, Vaccines Group Lead, Penn Institute for RNA Innovation, University of Pennsylvania
Scientists have long been trying to develop a vaccine for respiratory syncytial virus (RSV), and it looks like Pfizer are closing in on this goal, based on the latest clinical trial data in newborns which they released in November. Pfizer have developed a protein-based vaccine against the F protein of RSV, which they are giving to pregnant women. It turns out that it induces a robust immune response after the administration of a single shot and it seems to be highly protective in newborns. The efficacy was over 80% after 90 days, so it protected very well against severe disease, and even though this dropped a little after six month, it was still pretty high.
I think this has been a very important breakthrough, and very timely at the moment with both COVID-19, influenza and RSV circulating, which just shows the importance of having a vaccine which works well in both the very young and the very old.
The road to an RSV vaccine has also illustrated the importance of teamwork in 21st century vaccine development. You need people with different backgrounds to solve these challenges – microbiologists, immunologists and structural biologists working together to understand how viruses work, and how our immune system induces protective responses against certain viruses. It has been this kind of teamwork which has yielded the findings that targeting the prefusion stabilized form of the F protein in RSV induces much stronger and highly protective immune responses.
Gene therapy shows its potential
Nicole Paulk, Assistant Professor of Gene Therapy at the University of California, San Francisco
The recent US Food and Drug Administration (FDA) approval of Hemgenix, a gene therapy for hemophilia B, is big for a lot of reasons. While hemophilia is absolutely a rare disease, it is astronomically more common than the first two approvals – Luxturna for RPE65-meidated inherited retinal dystrophy and Zolgensma for spinal muscular atrophy - so many more patients will be treated with this. In terms of numbers of patients, we are now starting to creep up into things that are much more common, which is a huge step in terms of our ability to scale the production of an adeno-associated virus (AAV) vector for gene therapy.
Hemophilia is also a really special patient population because this has been the darling indication for AAV gene therapy for the last 20 to 30 years. AAV trafficks to the liver so well, it’s really easy for us to target the tissues that we want. If you look at the numbers, there have been more gene therapy scientists working on hemophilia than any other condition. There have just been thousands and thousands of us working on gene therapy indications for the last 20 or 30 years, so to see the first of these approvals make it, feels really special.
I am sure it is even more special for the patients because now they have a choice – do I want to stay on my recombinant factor drug that I need to take every day for the rest of my life, or right now I could get a one-time infusion of this virus and possibly experience curative levels of expression for the rest of my life. And this is just the first one for hemophilia, there’s going to end up being a dozen gene therapies within the next five years, targeted towards different hemophilias.
Every single approval is momentous for the entire field because it gets investors excited, it gets companies and physicians excited, and that helps speed things up. Right now, it's still a challenge to produce enough for double digit patients. But with more interest comes the experiments and trials that allow us to pick up the knowledge to scale things up, so that we can go after bigger diseases like diabetes, congestive heart failure, cancer, all of these much bigger afflictions.
Treating Thickened Hearts
John Spertus, Professor in Metabolic and Vascular Disease Research, UMKC School of Medicine
Hypertrophic cardiomyopathy (HCM) is a disease that causes your heart muscle to enlarge, and the walls of your heart chambers thicken and reduce in size. Because of this, they cannot hold as much blood and may stiffen, causing some sufferers to experience progressive shortness of breath, fatigue and ultimately heart failure.
So far we have only had very crude ways of treating it, using beta blockers, calcium channel blockers or other medications which cause the heart to beat less strongly. This works for some patients but a lot of time it does not, which means you have to consider removing part of the wall of the heart with surgery.
Earlier this year, a trial of a drug called mavacamten, became the first study to show positive results in treating HCM. What is remarkable about mavacamten is that it is directed at trying to block the overly vigorous contractile proteins in the heart, so it is a highly targeted, focused way of addressing the key problem in these patients. The study demonstrated a really large improvement in patient quality of life where they were on the drug, and when they went off the drug, the quality of life went away.
Some specialists are now hypothesizing that it may work for other cardiovascular diseases where the heart either beats too strongly or it does not relax well enough, but just having a treatment for HCM is a really big deal. For years we have not been very aggressive in identifying and treating these patients because there have not been great treatments available, so this could lead to a new era.
Regenerating Organs
David Andrijevic, Associate Research Scientist in neuroscience at Yale School of Medicine
As soon as the heartbeat stops, a whole chain of biochemical processes resulting from ischemia – the lack of blood flow, oxygen and nutrients – begins to destroy the body’s cells and organs. My colleagues and I at Yale School of Medicine have been investigating whether we can recover organs after prolonged ischemia, with the main goal of expanding the organ donor pool.
Earlier this year we published a paper in which we showed that we could use technology to restore blood circulation, other cellular functions and even heart activity in pigs, one hour after their deaths. This was done using a perfusion technology to substitute heart, lung and kidney function, and deliver an experimental cell protective fluid to these organs which aimed to stop cell death and aid in the recovery.
One of the aims of this technology is that it can be used in future to lengthen the time window for recovering organs for donation after a person has been declared dead, a logistical hurdle which would allow us to substantially increase the donor pool. We might also be able to use this cell protective fluid in studies to see if it can help people who have suffered from strokes and myocardial infarction. In future, if we managed to achieve an adequate brain recovery – and the brain, out of all the organs, is the most susceptible to ischemia – this might also change some paradigms in resuscitation medicine.
Antibody-Drug Conjugates for Cancer
Yosi Shamay, Cancer Nanomedicine and Nanoinformatics researcher at the Technion Israel Institute of Technology
For the past four or five years, antibody-drug conjugates (ADCs) - a cancer drug where you have an antibody conjugated to a toxin - have been used only in patients with specific cancers that display high expression of a target protein, for example HER2-positive breast cancer. But in 2022, there have been clinical trials where ADCs have shown remarkable results in patients with low expression of HER2, which is something we never expected to see.
In July 2022, AstraZeneca published the results of a clinical trial, which showed that an ADC called trastuzumab deruxtecan can offer a very big survival benefit to breast cancer patients with very little expression of HER2, levels so low that they would be borderline undetectable for a pathologist. They got a strong survival signal for patients with very aggressive, metastatic disease.
I think this is very interesting and important because it means that it might pave the way to include more patients in clinical trials looking at ADCs for other cancers, for example lymphoma, colon cancer, lung cancers, even if they have low expression of the protein target. It also holds implications for CAR-T cells - where you genetically engineer a T cell to attack the cancer - because the concept is very similar. If we now know that an ADC can have a survival benefit, even in patients with very low target expression, the same might be true for T cells.
Look back further: Breakthroughs of 2021
https://leaps.org/6-biotech-breakthroughs-of-2021-that-missed-the-attention-they-deserved/
For this podcast episode, my guest is Raina Plowright, one of the world’s leading researchers when it comes to how and why viruses sometimes jump from bats to humans. The intuition may be that bats are the bad guys in this situation, but the real culprits are more likely humans and ways that we intrude on nature.
Plowright is a Cornell Atkinson Scholar and professor at Cornell in the Department of Public and Ecosystem Health in the College of Veterinary Medicine. Read her full bio here. For a shorter (and lightly edited) version of this conversation, you can check out my Q&A interview with Plowright in the single-issue magazine, One Health / One Planet, published earlier this month by Leaps.org in collaboration with the Aspen Institute and the Science Philanthropy Alliance.
In the episode, Plowright tells me about her global research team that is busy studying the complex chain of events in between viruses originating in bats and humans getting infected with those viruses. She’s collecting samples from bats in Asia, Africa and Australia, which sounds challenging enough, but now consider the diligence required to parse out 1400 different bat species.
We also discuss a high-profile paper that she co-authored last month arguing for greater investment in preventing pandemics in the first place instead of the current approach, which basically puts all of our eggs in the basket of trying to respond to these outbreaks after the fact. Investing in pandemic prevention is a small price to pay compared with millions of people killed and trillions of dollars spent during the response to COVID-19.
Listen to the Episode
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Raina Plowright, a disease ecologist at Cornell University, is taking blood and urine samples from hundreds of animals and using GPS tags to follow their movement.
Kelly Gorham
Starting this summer, the public buses in the Oberhaching suburb of Munich, Germany, won’t have to be plugged in to charge overnight anymore. Stefan Schelle, the mayor of Oberhaching, is taking advantage of the fact that an innovative startup has its offices in his community: Magment, short for “magnetizing cement,” will install its underground charging pad in the coming months. As soon as that happens, the buses will charge while they wait at the city’s main station or while stored at their overnight quarters.
In his light-filled office, Magment’s co-founder and CEO, Mauricio Esguerra, demonstrates how the new technology works: The lights on his black model car only flash when he puts the miniature Porsche directly atop the induction plate. “This works just like when you charge your iPhone on its charging pad or heat a pot on an induction range. People don’t have to be afraid of magnetic fields or anything like that,” says the 60-year-old Colombia-born entrepreneur. “The induction only gets activated when the storage battery is placed directly on top.
Patented by Esguerra, the “magnetizing concrete” is able to target the charge quite precisely. The batteries will be mounted in a box underneath the vehicles such as the retrofitted public buses. “Look, here’s one passing by,” says Esguerra, pointing out the window as a blue city bus rides past his office.
An invention finds its purpose
Esguerra grew up in Bogotá, studied physics at the Technical University Munich where he fell in love with a German woman, and started a family in her home country. For 15 years, he developed magnetic products, including the magnetizing cement, for Siemens, Europe’s largest industrial manufacturing company. The patent belonged to Siemens, of course. “But there were hardly any electric vehicles yet,” Esguerra says, “and Siemens didn’t quite know what to do with this invention.”
Esguerra changed companies a few times but, in 2015, he got an offer from Siemens. The patent for the magnetizing cement was expiring and Siemens wasn’t interested in keeping it. Would he, as the inventor, want it back? “I did not hesitate a second,” Esguerra remembers with a smile. “I’m a magnetician at heart.” That same year, he founded Magment to finally make use of the technology he created 20 years ago.
To demonstrate how his cement is made, he opens the lid of a plastic bucket filled with cement powder. Mixed in are fingernail-sized black pieces, so-called ferrites, mainly consisting of three ceramic oxides: iron, nickel and zinc. Conventionally, they are used in electronics such as cell phones, computers and cables. Molded in concrete, ferrites create a magnetic field that can transport charge to a vehicle, potentially eliminating range anxiety for EV drivers.
Molded in concrete, ferrites create a magnetic field that can transport charge to a vehicle, potentially eliminating range anxiety for EV drivers.
Magment
“Ferrites have extremely high rejection rates,” Esguerra adds. “It’s comparable to other ceramics: As soon as there is a small tear or crack, the material is rejected. We are talking about a rejection pile of 500,000 tons per year worldwide. There are mountains of unused materials.”
Exactly this fact was the starting point of his research at Siemens: “What can we do with this energy-intensive material? Back then, it was crushed up and mixed into the cement for building streets, without adding any function.” Today, too, the Magment material can simply be mixed with the conventional material and equipment of the cement industry. “We take advantage of the fact that we don’t have to build factories and don’t have high transportation costs."
In addition to saving resources, recycled ferrite also makes concrete more durable.
No plugs, no charging breaks
A young intern in the office next door winds cables around a new coil. These coils will later be lowered underground in a box, connected to the grid and encased in magnetizing concrete. The recipient box looks similar; it’s another coil but smaller, and it will be mounted underneath the carriage of the vehicle. For a car, the battery box would be 25 by 25 centimeters (about 10 inches), for a scooter five by five centimeters (about two inches).
Esguerra pushes an electric scooter into a cemented scooter rack next to his office. The charging pad is invisible. A faint beep is the only sign that it has started charging. “Childs play!” Esguerra says. “Even when someone puts in the scooter a little crooked, the charge still works. Our efficiency rate is up to 96 percent.” From this summer on, hotel chains in Munich will try out this system with their rental scooters, at a price of about 500 Euros per charging station.
Compared to plug-in charging, Magment’s benefits include smaller batteries that charge slower and, therefore, gentler, so they may last longer. Nobody needs to plug in the vehicles manually anymore. “Personally, I’ve had an EV for six years,” Esguerra says, “and how often does it happen that I forgot to plug it in overnight and then start out with a low charge in the morning? Once people get used to the invisible charging system, it will become the norm.“
There are also downsides: Most car companies aren’t ready for the new technology. Hyundai is the first carmaker that announced plans to equip some new models with inductive charging capability. “How many cars are electrified worldwide?” Esguerra asks and gives the answer himself: “One percent. And how many forklifts are electrified? More than 70 percent!” Therefore, Magment focuses on charging forklifts, e-scooters and buses.
Magment has focused most of its efforts on charging forklifts and other vehicle types that are entirely or predominantly electric, unlike cars.
Magment
On the morning of my visit to Esguerra’s office, a developer of the world’s third-biggest forklift manufacturer is there to inspect how the technology works on the ground. In the basement, a Magment engineer drives an electric forklift over a testbed with invisible charging coils, turning on the green charging light. Esguerra opens the interior of the forklift and points out the two batteries. “With our system, the forklift will only need one battery.” The savings, about 7,000 Euro per forklift, will pay for the installation of Magment’s charging system in warehouses, Esguerra calculates. “Less personnel and no unnecessary wait times for charging will lead to further savings,” he says.
To implement the new technology as efficiently as possible, Magment engineers began recording the transport routes of forklifts in warehouses. “It looks like spaghetti diagrams,” Esguerra explains. “Soon you get the areas where the forklifts pass or wait most frequently. This is where you install the chargers underground.” The forklifts will charge while in use, without having to pause for charging breaks. The method could also work for robots, for instance, in warehouses and distribution centers.
Roads of the future could be electric
Potential disadvantages might become apparent once the technology is more broadly in use. Therefore investors were initially reluctant, Esguerra admits. “Some are eager to be the first but most prefer to wait until the technology has been extensively used in real life.”
A clear hurdle today is that electrifying entire freeways with induction coils would cost at least 1 to 1.5 million Euros per kilometer. The German Department for Transportation even calculates overall costs of 14 to 47 million Euros per kilometer. So, the technology may only make sense for areas where vehicles pass or dwell the longest, like the Oberhaching train station or a busy interstate toll booth.
And yet, Magment is ramping up to compete with other companies that build larger inductive charging pads. The company just finished the first 20 meters of a testbed in Indiana, in partnership with the Purdue University and the Indiana Department of Transportation. Magment is poised to build “the world’s first contactless wireless-charging concrete pavement highway segment,” Purdue University announced.
The project, part of Purdue’s ASPIRE (Advancing Sustainability through Powered Infrastructure for Roadway Electrification) program, is financed by the National Science Foundation. “Indiana is known as the Crossroads of America, and we’re committed to fortifying our position as a transportation leader by innovating to support the emerging vehicle technology,” Governor Eric J. Holcomb said. If testing is successful, including the concrete’s capacity to charge heavy trucks operating at higher power (200 kilowatts and above), Indiana plans to identify a highway segment to install Magment’s charging pads. The earliest would be 2023 at best.
In the meantime, buses in the Californian Antelope Valley, trams at Hollywood's Universal Studios and transit buses in Tampa, Florida, are already charging with inductive technology developed by Wave, a company spun out of Utah State University. In Michigan, Governor Gretchen Whitmer announced plans to build a test route for vehicles to charge while driving, in collaboration with the Israel-based company Electreon, and this year contracted to build the first road-based charging system in the U.S. The state is providing support through an innovative grant program.
Costs remain one of the biggest obstacles, but Esguerra’s vision includes the potential that toll roads could charge a premium for inductive charging capabilities. “And in reverse, a driver who has too much energy could feed his surplus into the grid while driving,” Esguerra dreams.
Meanwhile, Wave’s upcoming big projects are moving trucks along a route in Southern California and running a UPS route between Seattle and Portland. Wave CTO Michael Masquelier describes the inductive power transfer his company champions as “similar to a tuning fork. By vibrating that fork, you sent energy through the air and it is received by another tuning fork across the room. So it’s similar to that, but it’s magnetic energy versus sound energy.”
He hopes to partner with Magment, saying that “the magnetizing cement makes installation easier and improves the energy efficiency.” More research is needed to evaluate which company’s technology will prove to be the most efficient, practical, and cost-effective.
Esguerra’s vision includes the potential that toll roads could charge a premium for inductive charging capabilities. “And in reverse, a driver who has too much energy could feed his surplus into the grid while driving,” Esguerra dreams.
The future will soon arrive in the idyllic town of Bad Staffelstein, a quaint tourist destination in the Upper Franconia region of Germany. Visitors will be taken to and from the main station and the popular thermal bath by driverless shuttles. Together with the University of Wuppertal, the regional government of Upper Franconia wants to turn its district into “the center of autonomous driving.” Magment is about to install inductive charging pads at the shuttle stations and the thermal bath, eliminating the need for the shuttles to stop for charging times. No more drivers, no cable, no range anxiety. Masquelier believes that “wireless and autonomous driving go hand in hand.” Science fiction? It will become science reality in spring 2023.
CORRECTION: An earlier version of the story erroneously mentioned that Electreon required overhead cables.