Nine experts break down the biggest biotech and health breakthroughs that didn't get the attention they deserved in 2022.
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/
Theo, an 18-month-old in rural Nebraska, walks with his father in their backyard. For many toddlers, the barriers to accessing COVID-19 vaccines are many, such as few locations giving vaccines to very young children.
Children are at risk
Data presented at the most recent FDA advisory panel on COVID-19 vaccines showed that in the last year infants under six months had the third highest rate of hospitalization. “From the beginning, the message has been that kids don’t get COVID, and then the message was, well kids get COVID, but it’s not serious,” says Elias Kass, a pediatrician in Seattle. “Then they waited so long on the initial vaccines that by the time kids could get vaccinated, the majority of them had been infected.”
A closer look at the data from the CDC also reveals that from January 2022 to January 2023 children aged 6 to 23 months were more likely to be hospitalized than all other vaccine eligible pediatric age groups.
“We sort of forced an entire generation of kids to be infected with a novel virus and just don't give a shit, like nobody cares about kids,” Kass says. In some cases, COVID has wreaked havoc with the immune systems of very young children at his practice, making them vulnerable to other illnesses, he said. “And now we have kids that have had COVID two or three times, and we don’t know what is going to happen to them.”
Jumping through hurdles
Children under five were the last group to have an emergency use authorization (EUA) granted for the COVID-19 vaccine, a year and a half after adult vaccine approval. In June 2022, 30,000 sites were initially available for children across the country. Six months later, when boosters became available, there were only 5,000.
Currently, only 3.8% of children under two have completed a primary series, according to the CDC. An even more abysmal 0.2% under two have gotten a booster.
Ariadne Labs, a health center affiliated with Harvard, is trying to understand why these gaps exist. In conjunction with Boston Children’s Hospital, they have created a vaccine equity planner that maps the locations of vaccine deserts based on factors such as social vulnerability indexes and transportation access.
“People are having to travel farther because the sites are just few and far between,” says Benjy Renton, a research assistant at Ariadne.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. When the boosters first came out she expected her toddler could get it close to home, but her husband had to drive Charlee four hours roundtrip.
This experience hasn’t been uncommon, especially in rural parts of the U.S. If parents wanted vaccines for their young children shortly after approval, they faced the prospect of loading babies and toddlers, famous for their calm demeanor, into cars for lengthy rides. The situation continues today. Mrs. Smith*, a grant writer and non-profit advisor who lives in Idaho, is still unable to get her child the bivalent booster because a two-hour one-way drive in winter weather isn’t possible.
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited.
Protect Their Future (PTF), a grassroots organization focusing on advocacy for the health care of children, hears from parents several times a week who are having trouble finding vaccines. The vaccine rollout “has been a total mess,” says Tamara Lea Spira, co-founder of PTF “It’s been very hard for people to access vaccines for children, particularly those under three.”
Seventeen states have passed laws that give pharmacists authority to vaccinate as young as six months. Under federal law, the minimum age in other states is three. Even in the states that allow vaccination of toddlers, each pharmacy chain varies. Some require prescriptions.
It takes time to make phone calls to confirm availability and book appointments online. “So it means that the parents who are getting their children vaccinated are those who are even more motivated and with the time and the resources to understand whether and how their kids can get vaccinated,” says Tiffany Green, an associate professor in population health sciences at the University of Wisconsin at Madison.
Green adds, “And then we have the contraction of vaccine availability in terms of sites…who is most likely to be affected? It's the usual suspects, children of color, disabled children, low-income children.”
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited. In Bibb County, Ala., vaccinations take place only on Wednesdays from 1:45 to 3:00 pm.
“People who are focused on putting food on the table or stressed about having enough money to pay rent aren't going to prioritize getting vaccinated that day,” says Julia Raifman, assistant professor of health law, policy and management at Boston University. She created the COVID-19 U.S. State Policy Database, which tracks state health and economic policies related to the pandemic.
Most states in the U.S. lack paid sick leave policies, and the average paid sick days with private employers is about one week. Green says, “I think COVID should have been a wake-up call that this is necessary.”
Maskless waiting rooms
For her son, Holmes spent hours making phone calls but could uncover no clear answers. No one could estimate an arrival date for the booster. “It disappoints me greatly that the process for locating COVID-19 vaccinations for young children requires so much legwork in terms of time and resources,” she says.
In January, she found a pharmacy 30 minutes away that could vaccinate Theo. With her son being too young to mask, she waited in the car with him as long as possible to avoid a busy, maskless waiting room.
Kids under two, such as Theo, are advised not to wear masks, which make it too hard for them to breathe. With masking policies a rarity these days, waiting rooms for vaccines present another barrier to access. Even in healthcare settings, current CDC guidance only requires masking during high transmission or when treating COVID positive patients directly.
“This is a group that is really left behind,” says Raifman. “They cannot wear masks themselves. They really depend on others around them wearing masks. There's not even one train car they can go on if their parents need to take public transportation… and not risk COVID transmission.”
Yet another challenge is presented for those who don’t speak English or Spanish. According to Translators without Borders, 65 million people in America speak a language other than English. Most state departments of health have a COVID-19 web page that redirects to the federal vaccines.gov in English, with an option to translate to Spanish only.
The main avenue for accessing information on vaccines relies on an internet connection, but 22 percent of rural Americans lack broadband access. “People who lack digital access, or don’t speak English…or know how to navigate or work with computers are unable to use that service and then don’t have access to the vaccines because they just don’t know how to get to them,” Jirmanus, an affiliate of the FXB Center for Health and Human Rights at Harvard and a member of The People’s CDC explains. She sees this issue frequently when working with immigrant communities in Massachusetts. “You really have to meet people where they’re at, and that means physically where they’re at.”
Equitable solutions
Grassroots and advocacy organizations like PTF have been filling a lot of the holes left by spotty federal policy. “In many ways this collective care has been as important as our gains to access the vaccine itself,” says Spira, the PTF co-founder.
PTF facilitates peer-to-peer networks of parents that offer support to each other. At least one parent in the group has crowdsourced information on locations that are providing vaccines for the very young and created a spreadsheet displaying vaccine locations. “It is incredible to me still that this vacuum of information and support exists, and it took a totally grassroots and volunteer effort of parents and physicians to try and respond to this need.” says Spira.
Kass, who is also affiliated with PTF, has been vaccinating any child who comes to his independent practice, regardless of whether they’re one of his patients or have insurance. “I think putting everything on retail pharmacies is not appropriate. By the time the kids' vaccines were released, all of our mass vaccination sites had been taken down.” A big way to help parents and pediatricians would be to allow mixing and matching. Any child who has had the full Pfizer series has had to forgo a bivalent booster.
“I think getting those first two or three doses into kids should still be a priority, and I don’t want to lose sight of all that,” states Renton, the researcher at Ariadne Labs. Through the vaccine equity planner, he has been trying to see if there are places where mobile clinics can go to improve access. Renton continues to work with local and state planners to aid in vaccine planning. “I think any way we can make that process a lot easier…will go a long way into building vaccine confidence and getting people vaccinated,” Renton says.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. Her husband had to drive four hours roundtrip to get the boosters for Charlee.
Michelle Baltes-Breitwisch
Other changes need to come from the CDC. Even though the CDC “has this historic reputation and a mission of valuing equity and promoting health,” Jirmanus says, “they’re really failing. The emphasis on personal responsibility is leaving a lot of people behind.” She believes another avenue for more equitable access is creating legislation for upgraded ventilation in indoor public spaces.
Given the gaps in state policies, federal leadership matters, Raifman says. With the FDA leaning toward a yearly COVID vaccine, an equity lens from the CDC will be even more critical. “We can have data driven approaches to using evidence based policies like mask policies, when and where they're most important,” she says. Raifman wants to see a sustainable system of vaccine delivery across the country complemented with a surge preparedness plan.
With the public health emergency ending and vaccines going to the private market sometime in 2023, it seems unlikely that vaccine access is going to improve. Now more than ever, ”We need to be able to extend to people the choice of not being infected with COVID,” Jirmanus says.
*Some names were changed for privacy reasons.
Last month, a paper published in Cell by Harvard biologist David Sinclair explored root cause of aging, as well as examining whether this process can be controlled. We talked with Dr. Sinclair about this new research.
Show links:
Dr. Sinclair's paper, published last month in Cell.
Recent pre-print paper - not yet peer reviewed - showing that mice treated with Yamanaka factors lived longer than the control group.
Dr. Sinclair's podcast.
Previous research on aging and DNA mutations.
Dr. Sinclair's book, Lifespan.
Harvard Medical School