Tiny, Injectable Robots Could Be the Future of Brain Treatments
In the 1966 movie "Fantastic Voyage," actress Raquel Welch and her submarine were shrunk to the size of a cell in order to eliminate a blood clot in a scientist's brain. Now, 55 years later, the scenario is becoming closer to reality.
California-based startup Bionaut Labs has developed a nanobot about the size of a grain of rice that's designed to transport medication to the exact location in the body where it's needed. If you think about it, the conventional way to deliver medicine makes little sense: A painkiller affects the entire body instead of just the arm that's hurting, and chemotherapy is flushed through all the veins instead of precisely targeting the tumor.
"Chemotherapy is delivered systemically," Bionaut-founder and CEO Michael Shpigelmacher says. "Often only a small percentage arrives at the location where it is actually needed."
But what if it was possible to send a tiny robot through the body to attack a tumor or deliver a drug at exactly the right location?
Several startups and academic institutes worldwide are working to develop such a solution but Bionaut Labs seems the furthest along in advancing its invention. "You can think of the Bionaut as a tiny screw that moves through the veins as if steered by an invisible screwdriver until it arrives at the tumor," Shpigelmacher explains. Via Zoom, he shares the screen of an X-ray machine in his Culver City lab to demonstrate how the half-transparent, yellowish device winds its way along the spine in the body. The nanobot contains a tiny but powerful magnet. The "invisible screwdriver" is an external magnetic field that rotates that magnet inside the device and gets it to move and change directions.
The current model has a diameter of less than a millimeter. Shpigelmacher's engineers could build the miniature vehicle even smaller but the current size has the advantage of being big enough to see with bare eyes. It can also deliver more medicine than a tinier version. In the Zoom demonstration, the micorobot is injected into the spine, not unlike an epidural, and pulled along the spine through an outside magnet until the Bionaut reaches the brainstem. Depending which organ it needs to reach, it could be inserted elsewhere, for instance through a catheter.
"The hope is that we can develop a vehicle to transport medication deep into the body," says Max Planck scientist Tian Qiu.
Imagine moving a screw through a steak with a magnet — that's essentially how the device works. But of course, the Bionaut is considerably different from an ordinary screw: "At the right location, we give a magnetic signal, and it unloads its medicine package," Shpigelmacher says.
To start, Bionaut Labs wants to use its device to treat Parkinson's disease and brain stem gliomas, a type of cancer that largely affects children and teenagers. About 300 to 400 young people a year are diagnosed with this type of tumor. Radiation and brain surgery risk damaging sensitive brain tissue, and chemotherapy often doesn't work. Most children with these tumors live less than 18 months. A nanobot delivering targeted chemotherapy could be a gamechanger. "These patients really don't have any other hope," Shpigelmacher says.
Of course, the main challenge of the developing such a device is guaranteeing that it's safe. Because tissue is so sensitive, any mistake could risk disastrous results. In recent years, Bionaut has tested its technology in dozens of healthy sheep and pigs with no major adverse effects. Sheep make a good stand-in for humans because their brains and spines are similar to ours.
The Bionaut device is about the size of a grain of rice.
Bionaut Labs
"As the Bionaut moves through brain tissue, it creates a transient track that heals within a few weeks," Shpigelmacher says. The company is hoping to be the first to test a nanobot in humans. In December 2022, it announced that a recent round of funding drew $43.2 million, for a total of 63.2 million, enabling more research and, if all goes smoothly, human clinical trials by early next year.
Once the technique has been perfected, further applications could include addressing other kinds of brain disorders that are considered incurable now, such as Alzheimer's or Huntington's disease. "Microrobots could serve as a bridgehead, opening the gateway to the brain and facilitating precise access of deep brain structure – either to deliver medication, take cell samples or stimulate specific brain regions," Shpigelmacher says.
Robot-assisted hybrid surgery with artificial intelligence is already used in state-of-the-art surgery centers, and many medical experts believe that nanorobotics will be the instrument of the future. In 2016, three scientists were awarded the Nobel Prize in Chemistry for their development of "the world's smallest machines," nano "elevators" and minuscule motors. Since then, the scientific experiments have progressed to the point where applicable devices are moving closer to actually being implemented.
Bionaut's technology was initially developed by a research team lead by Peer Fischer, head of the independent Micro Nano and Molecular Systems Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany. Fischer is considered a pioneer in the research of nano systems, which he began at Harvard University more than a decade ago. He and his team are advising Bionaut Labs and have licensed their technology to the company.
"The hope is that we can develop a vehicle to transport medication deep into the body," says Max Planck scientist Tian Qiu, who leads the cooperation with Bionaut Labs. He agrees with Shpigelmacher that the Bionaut's size is perfect for transporting medication loads and is researching potential applications for even smaller nanorobots, especially in the eye, where the tissue is extremely sensitive. "Nanorobots can sneak through very fine tissue without causing damage."
In "Fantastic Voyage," Raquel Welch's adventures inside the body of a dissident scientist let her swim through his veins into his brain, but her shrunken miniature submarine is attacked by antibodies; she has to flee through the nerves into the scientist's eye where she escapes into freedom on a tear drop. In reality, the exit in the lab is much more mundane. The Bionaut simply leaves the body through the same port where it entered. But apart from the dramatization, the "Fantastic Voyage" was almost prophetic, or, as Shpigelmacher says, "Science fiction becomes science reality."
This article was first published by Leaps.org on April 12, 2021.
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.”