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/
Sarah Watts's son Henry was born with spina bifida and can't stand or walk without assistance.
When our son Henry, now six, was diagnosed with spina bifida at his 20-week ultrasound, my husband and I were in shock. It took us more than a few minutes to understand what the doctor was telling us.
When Henry was diagnosed in 2012, postnatal surgery was still the standard of care – but that was about to change.
Neither of us had any family history of birth defects. Our fifteen-month-old daughter, June, was in perfect health.
But more than that, spina bifida – a malformation of the neural tube that eventually becomes the baby's spine – is woefully complex. The defect, the doctor explained, was essentially a hole in Henry's lower spine from which his spinal nerves were protruding – and because they were exposed to my amniotic fluid, those nerves were already permanently damaged. After birth, doctors could push the nerves back into his body and sew up the hole, but he would likely experience some level of paralysis, bladder and bowel dysfunction, and a buildup of cerebrospinal fluid that would require a surgical implant called a shunt to correct. The damage was devastating – and irreversible.
We returned home with June and spent the next few days cycling between disbelief and total despair. But within a week, the maternal-fetal medicine specialist who diagnosed Henry called us up and gave us the first real optimism we had felt in days: There was a new, experimental surgery for spina bifida that was available in just a handful of hospitals around the country. Rather than waiting until birth to repair the baby's defect, some doctors were now trying out a prenatal repair, operating on the baby via c-section, closing the defect, and then keeping the mother on strict bedrest until it was time for the baby to be delivered, just before term.
This new surgery carried risks, he told us – but if it went well, there was a chance Henry wouldn't need a shunt. And because repairing the defect during my pregnancy meant the spinal nerves were exposed for a shorter amount of time, that meant we'd be preventing nerve damage – and less nerve damage meant that there was a chance he'd be able to walk.
Did we want in? the doctor asked.
Had I known more about spina bifida and the history of its treatment, this surgery would have seemed even more miraculous. Not too long ago, the standard of care for babies born with spina bifida was to simply let them die without medical treatment. In fact, it wasn't until the early 1950s that doctors even attempted to surgically repair the baby's defect at all, instead of opting to let the more severe cases die of meningitis from their open wound. (Babies who had closed spina bifida – a spinal defect covered by skin – sometimes survived past infancy, but rarely into adulthood).
But in the 1960s and 1970s, as more doctors started repairing defects and the shunting technology improved, patients with spina bifida began to survive past infancy. When catheterization was introduced, spina bifida patients who had urinary dysfunction, as is common, were able to preserve their renal function into adulthood, and they began living even longer. Within a few decades, spina bifida was no longer considered a death sentence; people were living fuller, happier lives.
When Henry was diagnosed in 2012, postnatal surgery was still the standard of care – but that was about to change. The first major clinical trial for prenatal surgery and spina bifida, called Management of Myelomeningocele (MOMS) had just concluded, and its objective was to see whether repairing the baby's defect in utero would be beneficial. In the trial, doctors assigned eligible women to undergo prenatal surgery in the second trimester of their pregnancies and then followed up with their children throughout the first 30 months of the child's life.
The results were groundbreaking: Not only did the children in the surgery group perform better on motor skills and cognitive tests than did patients in the control group, only 40 percent of patients ended up needing shunts compared to 80 percent of patients who had postnatal surgery. The results were so overwhelmingly positive that the trial was discontinued early (and is now, happily, the medical standard of care). Our doctor relayed this information to us over the phone, breathless, and left my husband and me to make our decision.
After a few days of consideration, and despite the benefits, my husband and I actually ended up opting for the postnatal surgery instead. Prenatal surgery, although miraculous, would have required extensive travel for us, as well as giving birth in a city thousands of miles from home with no one to watch our toddler while my husband worked and I recovered. But other parents I met online throughout our pregnancy did end up choosing prenatal surgery for their children – and the majority of them now walk with little assistance and only a few require shunting.
Even more amazing to me is that now – seven years after Henry's diagnosis, and not quite a decade since the landmark MOMS trial – the standard of care could be about to change yet again.
Regardless of whether they have postnatal or prenatal surgery, most kids with spina bifida still experience some level of paralysis and rely on wheelchairs and walkers to move around. Now, researchers at UC Davis want to augment the fetal surgery with a stem cell treatment, using human placenta-derived mesenchymal stromal cells (PMSCs) and affixing them to a cellular scaffold on the baby's defect, which not only protects the spinal cord from further damage but actually encourages cellular regeneration as well.
The hope is that this treatment will restore gross motor function after the baby is born – and so far, in animal trials, that's exactly what's happening. Fetal sheep, who were induced with spinal cord injuries in utero, were born with complete motor function after receiving prenatal surgery and PMSCs. In 2017, a pair of bulldogs born with spina bifida received the stem cell treatment a few weeks after birth – and two months after surgery, both dogs could run and play freely, whereas before they had dragged their hind legs on the ground behind them. UC Davis researchers hope to bring this treatment into human clinical trials within the next year.
A century ago, a diagnosis of spina bifida meant almost certain death. Today, most children with spina bifida live into adulthood, albeit with significant disabilities. But thanks to research and innovation, it's entirely possible that within my lifetime – and certainly within Henry's – for the first time in human history, the disabilities associated with spina bifida could be a thing of the past.