A company uses AI to fight muscle loss and unhealthy aging
There’s a growing need to slow down the aging process. The world’s population is getting older and, according to one estimate, 80 million Americans will be 65 or older by 2040. As we age, the risk of many chronic diseases goes up, from cancer to heart disease to Alzheimer’s.
BioAge Labs, a company based in California, is using genetic data to help people stay healthy for longer. CEO Kristen Fortney was inspired by the genetics of people who live long lives and resist many age-related diseases. In 2015, she started BioAge to study them and develop drug therapies based on the company’s learnings.
The team works with special biobanks that have been collecting blood samples and health data from individuals for up to 45 years. Using artificial intelligence, BioAge is able to find the distinctive molecular features that distinguish those who have healthy longevity from those who don’t.
In December 2022, BioAge published findings on a drug that worked to prevent muscular atrophy, or the loss of muscle strength and mass, in older people. Much of the research on aging has been in worms and mice, but BioAge is focused on human data, Fortney says. “This boosts our chances of developing drugs that will be safe and effective in human patients.”
How it works
With assistance from AI, BioAge measures more than 100,000 molecules in each blood sample, looking at proteins, RNA and metabolites, or small molecules that are produced through chemical processes. The company uses many techniques to identify these molecules, some of which convert the molecules into charged atoms and then separating them according to their weight and charge. The resulting data is very complex, with many thousands of data points from patients being followed over the decades.
BioAge validates its targets by examining whether a pathway going awry is actually linked to the development of diseases, based on the company’s analysis of biobank health records and blood samples. The team uses AI and machine learning to identify these pathways, and the key proteins in the unhealthy pathways become their main drug targets. “The approach taken by BioAge is an excellent example of how we can harness the power of big data and advances in AI technology to identify new drugs and therapeutic targets,” says Lorna Harries, a professor of molecular genetics at the University of Exeter Medical School.
Martin Borch Jensen is the founder of Gordian Biotechnology, a company focused on using gene therapy to treat aging. He says BioAge’s use of AI allows them to speed up the process of finding promising drug candidates. However, it remains a challenge to separate pathologies from aspects of the natural aging process that aren’t necessarily bad. “Some of the changes are likely protective responses to things going wrong,” Jensen says. “Their data doesn’t…distinguish that so they’ll need to validate and be clever.”
Developing a drug for muscle loss
BioAge decided to focus on muscular atrophy because it affects many elderly people, making it difficult to perform everyday activities and increasing the risk of falls. Using the biobank samples, the team modeled different pathways that looked like they could improve muscle health. They found that people who had faster walking speeds, better grip strength and lived longer had higher levels of a protein called apelin.
Apelin is a peptide, or a small protein, that circulates in the blood. It is involved in the process by which exercise increases and preserves muscle mass. BioAge wondered if they could prevent muscular atrophy by increasing the amount of signaling in the apelin pathway. Instead of the long process of designing a drug, they decided to repurpose an existing drug made by another biotech company. This company, called Amgen, had explored the drug as a way to treat heart failure. It didn’t end up working for that purpose, but BioAge took note that the drug did seem to activate the apelin pathway.
BioAge tested its new, repurposed drug, BGE-105, and, in a phase 1 clinical trial, it protected subjects from getting muscular atrophy compared to a placebo group that didn’t receive the drug. Healthy volunteers over age 65 received infusions of the drug during 10 days spent in bed, as if they were on bed rest while recovering from an illness or injury; the elderly are especially vulnerable to muscle loss in this situation. The 11 people taking BGE-105 showed a 100 percent improvement in thigh circumference compared to 10 people taking the placebo. Ultrasound observations also revealed that the group taking the durg had enhanced muscle quality and a 73 percent increase in muscle thickness. One volunteer taking BGE-105 did have muscle loss compared to the the placebo group.
Heather Whitson, the director of the Duke University Centre for the study of aging and human development, says that, overall, the results are encouraging. “The clinical findings so far support the premise that AI can help us sort through enormous amounts of data and identify the most promising points for beneficial interventions.”
More studies are needed to find out which patients benefit the most and whether there are side effects. “I think further studies will answer more questions,” Whitson says, noting that BGE-105 was designed to enhance only one aspect of physiology associated with exercise, muscle strength. But exercise itself has many other benefits on mood, sleep, bones and glucose metabolism. “We don’t know whether BGE-105 will impact these other outcomes,” she says.
The future
BioAge is planning phase 2 trials for muscular atrophy in patients with obesity and those who have been hospitalized in an intensive care unit. Using the data from biobanks, they’ve also developed another drug, BGE-100, to treat chronic inflammation in the brain, a condition that can worsen with age and contributes to neurodegenerative diseases. The team is currently testing the drug in animals to assess its effects and find the right dose.
BioAge envisions that its drugs will have broader implications for health than treating any one specific disease. “Ultimately, we hope to pioneer a paradigm shift in healthcare, from treatment to prevention, by targeting the root causes of aging itself,” Fortney says. “We foresee a future where healthy longevity is within reach for all.”
Small changes in how a person talks could reveal Alzheimer’s earlier
Dave Arnold retired in his 60s and began spending time volunteering in local schools. But then he started misplacing items, forgetting appointments and losing his sense of direction. Eventually he was diagnosed with early stage Alzheimer’s.
“Hearing the diagnosis made me very emotional and tearful,” he said. “I immediately thought of all my mom had experienced.” His mother suffered with the condition for years before passing away. Over the last year, Arnold has worked for the Alzheimer’s Association as one of its early stage advisors, sharing his insights to help others in the initial stages of the disease.
Arnold was diagnosed sooner than many others. It's important to find out early, when interventions can make the most difference. One promising avenue is looking at how people talk. Research has shown that Alzheimer’s affects a part of the brain that controls speech, resulting in small changes before people show other signs of the disease.
Now, Canary Speech, a company based in Utah, is using AI to examine elements like the pitch of a person’s voice and their pauses. In an initial study, Canary analyzed speech recordings with AI and identified early stage Alzheimer’s with 96 percent accuracy.
Developing the AI model
Canary Speech’s CEO, Henry O’Connell, met cofounder Jeff Adams about 40 years before they started the company. Back when they first crossed paths, they were both living in Bethesda, Maryland; O’Connell was a research fellow at the National Institutes of Health studying rare neurological diseases, while Adams was working to decode spy messages. Later on, Adams would specialize in building mathematical models to analyze speech and sound as a team leader in developing Amazon's Alexa.
It wasn't until 2015 that they decided to make use of the fit between their backgrounds. ““We established Canary Speech in 2017 to build a product that could be used in multiple languages in clinical environments,” O'Connell says.
The need is growing. About 55 million people worldwide currently live with Alzheimer’s, a number that is expected to double by 2050. Some scientists think the disease results from a buildup of plaque in the brain. It causes mild memory loss at first and, over time, this issue get worse while other symptoms, such as disorientation and hallucinations, can develop. Treatment to manage the disease is more effective in the earlier stages, but detection is difficult since mild symptoms are often attributed to the normal aging process.
O’Connell and Adams specialize in the complex ways that Alzheimer’s effects how people speak. Using AI, their mathematical model analyzes 15 million data points every minute, focusing on certain features of speech such as pitch, pauses and elongation of words. It also pays attention to how the vibrations of vocal cords change in different stages of the disease.
To create their model, the team used a type of machine learning called deep neural nets, which looks at multiple layers of data - in this case, the multiple features of a person’s speech patterns.
“Deep neural nets allow us to look at much, much larger data sets built out of millions of elements,” O’Connell explained. “Through machine learning and AI, we’ve identified features that are very sensitive to an Alzheimer’s patient versus [people without the disease] and also very sensitive to mild cognitive impairment, early stage and moderate Alzheimer's.” Based on their learnings, Canary is able to classify the disease stage very quickly, O’Connell said.
“When we’re listening to sublanguage elements, we’re really analyzing the direct result of changes in the brain in the physical body,” O’Connell said. “The brain controls your vocal cords: how fast they vibrate, the expansion of them, the contraction.” These factors, along with where people put their tongues when talking, function subconsciously and result in subtle changes in the sounds of speech.
Further testing is needed
In an initial trial, Canary analyzed speech recordings from phone calls to a large U.S. health insurer. They looked at the audio recordings of 651 policyholders who had early stage Alzheimer’s and 1018 who did not have the condition, aiming for a representative sample of age, gender and race. They used this data to create their first diagnostic model and found that it was 96 percent accurate in identifying Alzheimer’s.
Christian Herff, an assistant professor of neuroscience at Maastricht University in the Netherlands, praised this approach while adding that further testing is needed to assess its effectiveness.
“I think the general idea of identifying increased risk for cognitive impairment based on speech characteristics is very feasible, particularly when change in a user’s voice is monitored, for example, by recording speech every year,” Herff said. He noted that this can only be a first indication, not a full diagnosis. The accuracy still needs to be validated in studies that follows individuals over a period of time, he said.
Toby Walsh, a professor of artificial intelligence at the University of New South Wales, also thinks Canary’s tool has potential but highlights that Canary could diagnose some people who don’t really have the disease. “This is an interesting and promising application of AI,” he said, “but these tools need to be used carefully. Imagine the anxiety of being misdiagnosed with Alzheimer’s.”
As with many other AI tools, privacy and bias are additional issues to monitor closely, Walsh said.
Other languages
A related issue is that not everyone is fluent in English. Mahnaz Arvaneh, a senior lecturer in automatic control and systems engineering at the University of Sheffield, said this could be a blind spot.
“The system may not be very accurate for those who have English as their second language as their speaking patterns would be different, and any issue might be because of language deficiency rather than cognitive issues,” Arvaneh said.
The team is expanding to multiple languages starting with Japanese and Spanish. The elements of the model that make up the algorithm are very similar, but they need to be validated and retrained in a different language, which will require access to more data.
Recently, Canary analyzed the phone calls of 233 Japanese patients who had mild cognitive impairment and 704 healthy people. Using an English model they were able to identify the Japanese patients who had mild cognitive impairment with 78 percent accuracy. They also developed a model in Japanese that was 45 percent accurate, and they’re continuing to train it with more data.
The future
Canary is using their model to look at other diseases like Huntington’s and Parkinson’s. They’re also collaborating with pharmaceuticals to validate potential therapies for Alzheimer’s. By looking at speech patterns over time, Canary can get an indication of how well these drugs are working.
Dave Arnold and his wife dance at his nephew’s wedding in Rochester, New York, ten years ago, before his Alzheimer's diagnosis.
Dave Arnold
Ultimately, they want to integrate their tool into everyday life. “We want it to be used in a smartphone, or a teleconference call so that individuals could be examined in their home,” O’Connell said. “We could follow them over time and work with clinical teams and hospitals to improve the evaluation of patients and contribute towards an accurate diagnosis.”
Arnold, the patient with early stage Alzheimer’s, sees great promise. “The process of getting a diagnosis is already filled with so much anxiety,” he said. “Anything that can be done to make it easier and less stressful would be a good thing, as long as it’s proven accurate.”
Gene therapy helps restore teen’s vision for first time
Story by Freethink
For the first time, a topical gene therapy — designed to heal the wounds of people with “butterfly skin disease” — has been used to restore a person’s vision, suggesting a new way to treat genetic disorders of the eye.
The challenge: Up to 125,000 people worldwide are living with dystrophic epidermolysis bullosa (DEB), an incurable genetic disorder that prevents the body from making collagen 7, a protein that helps strengthen the skin and other connective tissues.Without collagen 7, the skin is incredibly fragile — the slightest friction can lead to the formation of blisters and scarring, most often in the hands and feet, but in severe cases, also the eyes, mouth, and throat.
This has earned DEB the nickname of “butterfly skin disease,” as people with it are said to have skin as delicate as a butterfly’s wings.
The gene therapy: In May 2023, the FDA approved Vyjuvek, the first gene therapy to treat DEB.
Vyjuvek uses an inactivated herpes simplex virus to deliver working copies of the gene for collagen 7 to the body’s cells. In small trials, 65 percent of DEB-caused wounds sprinkled with it healed completely, compared to just 26 percent of wounds treated with a placebo.
“It was like looking through thick fog.” -- Antonio Vento Carvajal.
The patient: Antonio Vento Carvajal, a 14 year old living in Florida, was one of the trial participants to benefit from Vyjuvek, which was developed by Pittsburgh-based pharmaceutical company Krystal Biotech.
While the topical gene therapy could help his skin, though, it couldn’t do anything to address the severe vision loss Antonio experienced due to his DEB. He’d undergone multiple surgeries to have scar tissue removed from his eyes, but due to his condition, the blisters keep coming back.
“It was like looking through thick fog,” said Antonio, noting how his impaired vision made it hard for him to play his favorite video games. “I had to stand up from my chair, walk over, and get closer to the screen to be able to see.”
The idea: Encouraged by how Antonio’s skin wounds were responding to the gene therapy, Alfonso Sabater, his doctor at the Bascom Palmer Eye Institute, reached out to Krystal Biotech to see if they thought an alternative formula could potentially help treat his patient’s eyes.
The company was eager to help, according to Sabater, and after about two years of safety and efficacy testing, he had permission, under the FDA’s compassionate use protocol, to treat Antonio’s eyes with a version of the topical gene therapy delivered as eye drops.
The results: In August 2022, Sabater once again removed scar tissue from Antonio’s right eye, but this time, he followed up the surgery by immediately applying eye drops containing the gene therapy.
“I would send this message to other families in similar situations, whether it’s DEB or another condition that can benefit from genetic therapy. Don’t be afraid.” -- Yunielkys “Yuni” Carvajal.
The vision in Antonio’s eye steadily improved. By about eight months after the treatment, it was just slightly below average (20/25) and stayed that way. In March 2023, Sabater performed the same procedure on his young patient’s other eye, and the vision in it has also steadily improved.
“I’ve seen the transformation in Antonio’s life,” said Sabater. “He’s always been a happy kid. Now he’s very happy. He can function pretty much normally. He can read, he can study, he can play video games.”
Looking ahead: The topical gene therapy isn’t a permanent fix — it doesn’t alter Antonio’s own genes, so he has to have the eye drops reapplied every month. Still, that’s far less invasive than having to undergo repeated surgeries.
Sabater is now working with Krystal Biotech to launch trials of the eye drops in other patients, and not just those with DEB. By changing the gene delivered by the therapy, he believes it could be used to treat other eye disorders that are far more common — Fuchs’ dystrophy, for example, affects the vision of an estimated 300 million people over the age of 30.
Antonio’s mother, Yunielkys “Yuni” Carvajal, meanwhile, has said that having her son be the first to receive the eye drops was “very scary,” but she’s hopeful others will take a chance on new gene therapies if given the opportunity.
“I would send this message to other families in similar situations, whether it’s DEB or another condition that can benefit from genetic therapy,” she said. “Don’t be afraid.”