Sweet Caroline: BCIs That Restore Sensation of Touch Show Long-Term Safety

“Touching hands, reaching out, touching me, touching you.”

The lead up to the chorus of Neil Diamond’s “Sweet Caroline” has become a ritual in stadiums and bars across America, celebrating one of the most universal human experiences: reaching out to touch another person.

For people living with paralysis after a spinal cord injury, that experience often disappears. Damage to the spinal cord not only interrupts movement but also severs the flow of sensory information from much of the body, leaving many unable to feel touch below the site of their injury.

While brain-computer interfaces (BCIs) already restore a measure of independence by translating thoughts into movement, allowing people to control robotic limbs, computers, and other assistive devices, they have long lacked something fundamental: touch. Now researchers report the strongest evidence yet that restoring artificial touch can be done safely over the long term.

In a study published in Science Translational Medicine, scientists followed five people with cervical spinal cord injuries who received tiny electrical pulses directly to the brain’s somatosensory cortex for periods ranging from nearly three years to a decade. Across more than 173 million stimulation pulses delivered over a combined 27 years of implanted use, the researchers found no serious stimulation-related adverse events while consistently restoring sensations of touch to participants’ hands.

One participant in the study described the difference after researchers restored an artificial sense of touch by stimulating his brain.

Charles Greenspon - BCI
Charles Greenspon, PhD, Assistant Professor of Neurological Surgery, The University of Chicago [The University of Chicago]

Instead of merely watching a hand grasp another person’s hand, he said, it felt as though he were shaking it himself. “It’s the difference between ‘I told a robotic arm to shake your hand’ and ‘I am shaking your hand,’” Charles Greenspon, PhD, assistant professor of neurological surgery at the University of Chicago and the study’s lead author, told Inside Precision Medicine. “That degree of embodiment is completely impossible without sensory feedback because you just don’t believe it’s yours.”

Creating touch

That sense of ownership—of a prosthetic becoming part of the body—is one of the biggest remaining challenges in neurotechnology. Companies including Neuralink, Precision Neuroscience, and Paradromics have largely focused on reading signals from the brain. Today’s most advanced BCIs excel at reading neural activity, decoding a person’s intentions to move a robotic arm or computer cursor. But they are largely one-way systems, sending nothing back to the brain.

Without sensory feedback, users must rely almost entirely on vision, making movements slower, less natural, and more mentally demanding. Restoring sensation by writing information back into the nervous system has remained a much greater challenge—not because the concept is new, but because evidence that repeated brain stimulation is safe over many years has been limited.

Although involving only five participants, the study is the largest and longest safety evaluation of intracortical microstimulation in humans. The findings address a major obstacle to the next generation of BCIs: proving that the brain can safely receive artificial sensory information over many years. If confirmed in larger clinical trials, the work could accelerate the development of truly bidirectional BCIs that both decode a person’s intentions and restore the sensory feedback that makes movement feel natural.

The researchers’ approach bypasses the damaged spinal cord entirely. Participants received two tiny microelectrode arrays implanted in the region of the somatosensory cortex responsible for hand sensation. Brief electrical pulses delivered through individual electrodes produced sensations that participants perceived as coming from specific locations on their hands.

“Once that device is in, we deliver tiny electrical pulses to the brain directly, and that creates the sensations,” Greenspon said. “The brain cannot functionally tell the difference between something that occurs at your hand and travels up your arm to the brain or directly stimulates the brain.”

Built to last

The researchers also wanted to know whether the implants would continue working after years of repeated use. Like any implanted medical device, microelectrode arrays gradually degrade.

The results suggest repeated stimulation does not accelerate that process. Detection thresholds increased only gradually, and even after a decade, about 60% of the electrodes in one participant could still reliably evoke touch sensations, while about two-thirds remained functional throughout the study. Researchers also found no relationship between how heavily individual electrodes were used and how quickly they deteriorated. “No company is claiming that these implants last forever,” Greenspon said. “It’s the same as a knee replacement.”

The study’s primary goal was straightforward: determine whether years of repeated stimulation would trigger seizures, damage brain tissue, or accelerate deterioration of the implanted electrodes. Across 623 hours of stimulation, participants experienced no seizures and no serious adverse events related to the stimulation itself.

Researchers also found no evidence that the electrical pulses damaged participants’ remaining natural sensation. The only stimulation-related side effects consisted of 53 brief episodes of lingering tingling or buzzing after stimulation ended, most resolving within seconds. “It’s one of the few times where you want a null result,” Greenspon said. “We just wanted to say, ‘Look, we didn’t find anything bad.’”

That absence of problems may ultimately be the study’s most important finding, providing the evidence regulators and device developers need before sensory feedback can become a standard feature of future BCIs.

Closing the brain’s feedback loop

For people who may eventually rely on BCIs outside the laboratory, restoring touch could prove just as important as restoring movement. Without sensory feedback, every movement requires constant visual attention. Greenspon compares the experience to leaving the dentist after a local anesthetic: “You can speak perfectly… It’s because you don’t know where your tongue is.”

Artificial touch changes something more subtle as well. Rather than operating a machine, users begin to experience a prosthetic as part of themselves. Researchers believe that sense of embodiment could make future prosthetic limbs not only more dexterous but also less mentally exhausting to use.

The next major challenge is restoring proprioception—the internal sense that tells us where our limbs are without looking. Current sensory BCIs cannot reproduce that ability. Researchers also hope future systems will deliver richer sensory information, allowing users to distinguish whether an object is soft or hard, rough or smooth, or beginning to slip from their grasp.

The findings arrive as brain-computer interfaces transition from academic laboratories to commercial development. Before sensory neuroprostheses become routine treatments, researchers will still need to conduct larger clinical studies.

For decades, BCI research has focused on teaching machines to understand the brain. The next generation may depend just as much on teaching the brain to understand the machine. If that happens, the most important advance may not be giving people the ability to control a prosthetic hand. It may be giving them the feeling that the hand is their own.

That is what made the participant’s handshake remarkable. The breakthrough wasn’t that a hand closed around another person’s. It was that, for the first time, it felt like their own handshake.

The post Sweet Caroline: BCIs That Restore Sensation of Touch Show Long-Term Safety appeared first on Inside Precision Medicine.

STAT+: GOP blocks effort to end Medicare test of AI prior authorization

WASHINGTON — A Senate vote to halt a Medicare pilot that uses artificial intelligence to approve or deny care failed along party lines on Thursday.

Republicans voted to block consideration of a Democratic-led measure, which would have stopped the Trump administration from employing prior authorization in original Medicare, where the practice is rarely allowed. The vote was 46 to 50.

The White House had pushed back against the Democratic bill. Medicare officials gave a handout to lawmakers’ offices on Tuesday outlining what they say are the benefits of the test, known as WISeR. 

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AI-Designed Synthetic CRISPR-Like Nucleases Show Activity in Cells

A new paper published in Science describes using artificial intelligence (AI) to design functional synthetic RNA-guided nucleases whose activity matches or exceeds that of natural enzymes. In the paper, titled “Structure and evolution-guided design of minimal RNA-guided nucleases,” the scientists wrote that the results “establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.”

The team includes scientists from Innovative Genomics Institute and the California Institute for Quantitative Bioscience, both at the University of California, Berkeley, and collaborators at other institutions.The findings highlight AI’s ability to expand the CRISPR toolbox to include RNA-guided nucleases with novel properties beyond those found in nature. It is a task that has been challenging for protein design methods because of the complexity of multi-domain proteins, “whose activity depends on coordinated RNA and DNA recognition, activation, and cleavage by distinct conformational states,” the scientists wrote. As such, seemingly small changes can disrupt enzyme activity. 

Sequence-based biological language models have been used to successfully design new nucleases by inferring sequence-function relationships, but they often produce versions of these proteins that closely resemble the reference sequences used to train them. Meanwhile, structure-guided rational design approaches, which “offer a robust strategy to sample highly divergent protein sequences” as well as “structures not found in nature” have been used to generate things like dynamic switches and DNA binders. However, designing complex proteins like RNA-guided nucleases with multiple functional domains and conformations has remained challenging for these methods.

In the Science paper, the scientists present an alternate strategy for generating novel functional proteins that combines the ESM Inverse Folding (ESM-IF1) model with evolution-informed residue constraints. As a test case, they used it to generate new variants for TnpB, a family of CRISPR-cas12-like nucleases that mediate RNA-guided DNA cleavage and regulate transcription among other tasks. Members of this enzyme family are “an attractive target for protein design because they couple programmable DNA targeting and a variety of natural functions to a minimal architecture,” the scientists explained in the paper.

The results showed that compared to sequence-based biological language models which generated proteins with binding domains with over 99% identity to natural homology, their approach created “DNA- and RNA-interacting lobes with AI-generated contacts that had 83% and 72% identity to their closest counterparts in nature.”

As part of the study, the scientists screened the activity of the designed proteins, dubbed SynTnpBs, first in the bacterial cells and then selected the most active ones for further testing in plant and human cells. They also used cryo-electron microscopy to determine the structures of the most divergent variants. Their analysis showed that many AI-designed nucleases either retained or surpassed the activity of natural TnpB in multiple cell types. Microscopy studies further revealed that the engineered proteins formed new electrostatic and hydrogen-bonding networks that stabilize interactions at the RNA-DNA interface across different conformations. 

The post AI-Designed Synthetic CRISPR-Like Nucleases Show Activity in Cells appeared first on GEN – Genetic Engineering and Biotechnology News.

STAT+: Despite earnings celebration, UnitedHealth signals more financial pain for employers

UnitedHealth Group smashed through investors’ earnings expectations in the second quarter, with executives confidently saying this new level of profit is durable for the foreseeable future.

The numbers lifted the company’s stock about 3% as it attempts to return to financial dominance under CEO Stephen Hemsley. But a string of comments made during the company’s earnings call on Thursday signals a more ominous path ahead for America’s businesses and workers.

More than 150 million Americans get their health coverage from a job. A new series from STAT chronicles how the costs of that insurance are stretching employers like never before. An increasing number of America’s small businesses are abandoning traditional health benefits completely, forcing workers to find alternative options.

Continue to STAT+ to read the full story…

Pete Hegseth’s announcement of annual testosterone screenings for service members divides medical experts

Medical experts are divided on Defense Secretary Pete Hegseth’s announcement that U.S. service members will undergo testosterone deficiency screenings with their annual physical exams. 

“War fighters aged 30 and older are going to be tested annually as part of their periodic health assessment,” said Hegseth in a video, posted with the caption “The High-T Department of War.” Elective testosterone testing will be available to younger service members, too, and if recommended, testosterone replacement therapy would be at the individual’s discretion. 

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See, Blind Mice: Consortium’s Drugs Restore Sight

A consortium led by scientists at the Institute for Bioengineering of Catalonia (IBEC) has developed a series of light-activated small molecule drugs that in preclinicial tests restored sight in blind mice. The team’s approach is based on photopharmacology, a technique for reversibly control drug activity using light.

The newly developed compounds, called prosthe6, mimic the function of light sensing photoreceptor cells, which degenerate in blinding diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).

The prosthe6 compounds target ON-bipolar neurons and in tests were found to successfully restore saccadic eye movements (optokinetic reflex) in blinded zebrafish larvae, a widely used model for studying visual acuity. Even more strikingly, the researchers demonstrated recovery of innate light-avoidance behavior in mouse models of age-related macular degeneration and retinitis pigmentosa.

Test results suggest that the prosthe6 compounds may be administered by injecting them in the eye, or administered as eye drops. In animal studies the photoswitchable molecules also showed promising preliminary safety profiles, pointing to the development of potential drug candidates for restoring vision in patients with degenerative retinal diseases, without the need for genetic manipulation or implanted devices. Importantly, these compounds are designed to work under normal lighting conditions and do not require light-enhancing devices as optogenetics. They are small, water-soluble molecules that respond to ordinary visible or white light, such as indoor lighting or daylight, without requiring intense or specialized light sources.

“These molecules do not cure blindness, because they do not address the cause of photoreceptor degeneration,” said study co-lead Pau Gorostiza, PhD, ICREA Research Professor at IBEC, leader of the Nanoprobes and Nanoswitches group, member of CIBER-BBN. “But they are remarkably effective at restoring sight, and they do so using a very simple and potentially patient-friendly approach.”

Rosalba Sortino, former PhD student at the University de Barcelona, and currently post-doctoral researcher at Gorostiza’s group at IBEC, added, “Our goal was to restore vision using a molecular mechanism that is as close as possible to how the healthy retina works … Instead of bypassing retinal processing, we aimed to reactivate it right at the same level of the retinal circuit than the lost photoreceptor cells.”

Sortino is co-first author of the team’s published paper in Journal of the American Chemical Society, titled “Restoration of saccadic eye movements and visually guided behavior in ambient white light with photoswitchable small molecules.”

Diseases such as age-related macular degeneration and retinitis pigmentosa affect 200 million people worldwide and are the leading causes of visual impairment and blindness. Beyond the personal impact on quality of life and independence, vision loss places a global economic burden estimated at over US$400 billion per year in healthcare costs and lost productivity.

Researchers Rosalba Sortino (left) and Joaquin Martinez Tambella (right) working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Sortino is a post-doctoral researcher at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC).]
Researchers Rosalba Sortino (left) and Joaquin Martinez Tambella (right) working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Sortino is a post-doctoral researcher at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC)]

In many of these conditions, photoreceptor (PhR) cells—the retina’s light detectors—progressively degenerate and die. Although the downstream retinal neuronal circuitry remains largely intact and functionally viable, it no longer receives the light signals needed to drive visual processing towards the brain. This opportunity has fueled intense research efforts to develop treatments capable of restoring light sensitivity to the eye. Current strategies include gene therapy—effective only for a very small subset of patients with specific mutations—and electronic retinal prostheses, which are invasive, expensive, and require extensive training for effective use.

More recently, optogenetics and light-responsive drugs have entered clinical testing, the latter with encouraging safety results. “Photopharmacology can develop photoswitchable small molecules to restore vision impairment by conferring light sensitivity to ion channels that are widely expressed in the remaining inner retinal neurons, and a first-in-human clinical trial is ongoing,” the team noted. However, achieving high-quality vision at ambient illumination levels remains a major challenge.

The (IBEC)-led consortium has now developed a new class of photoswitchable small-molecule drugs that are capable of restoring key visual functions in animal models of blindness. The team’s photopharmacology-based technique involves modifying a drug’s chemical structure by adding a light-activated molecular switch, enabling control of the pharmacological action using light. “Unlike (opto)genetic manipulation and surgically implanted retinal electronic prostheses, pharmacotherapy is noninvasive, readily reversible, and can be upgraded when new drugs are approved,” the authors noted. “Medicines are preferred by patients, clinicians, and public healthcare systems, they  can be developed and manufactured at lower costs than other approaches and assessed by conventional regulatory procedures and clinical assays.”

The reported work builds on more than a decade of research and was carried out in collaboration with the team co-led by Pedro de la Villa at the University of Alcalá (UAH), as well as researchers from the Institut de Química Avançada de Catalunya (IQAC-CSIC), the University of Barcelona (UB), the Institute Ramón y Cajal of Health Research (IRYCIS), the Autonomous University of Barcelona (UAB), and the Fundació Eduard Soler.

Researcher Joaquin Martinez Tambella working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC).]
Researcher Joaquin Martinez Tambella working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC)]

The prosthe6 compounds work by acting on a specific type of retinal cells called ON bipolar cells, which normally receive signals from the photoreceptors. “In healthy vision, ON bipolar cells play a key role in passing on information about the presence of light to the rest of the visual circuit,” explained study co-lead de la Villa. “In degenerative eye diseases, although the photoreceptors are lost, much of this underlying circuitry remains intact but inactive. This creates a major therapeutic opportunity.”

By targeting a protein (mGlu6) in this preserved part of the retina, prosthe6 compounds can take over the role of the missing photoreceptors. “… we have targeted metabotropic glutamate 6 (mGlu6) receptors, which are exclusively expressed in ON bipolar cells (OBCs) and localized postsynaptic to PhR cells, thereby leveraging a privileged position to drive physiological visual circuit,” the investigators explained. When light enters the eye, the molecules respond by changing their shape, triggering signals inside the retina in a way that closely resembles natural vision. In this way, the drugs effectively act as “molecular prostheses,” helping the eye process light again without the need for implants or genetic modifications.

Healthy mice naturally prefer to remain in dark environments and instinctively avoid brightly lit areas, a behavior that relies entirely on a functional visual system. Blind mice, by contrast, lose this preference and move indistinctly between light and dark spaces, as they are unable to perceive light. The team showed that after treatment with prosthe6, blind mice once again showed a clear and spontaneous preference for dark areas, indicating that they could perceive light and use this information to guide their behavior.

This recovery occurred without any training and under light levels comparable to those found indoors or on an overcast day, demonstrating that the treatment restores functional light perception capable of driving natural, visually guided behavior.

Two lead compounds, prosthe6-12 and prosthe6-15, showed particularly promising results. The restored behaviors were observed not only after intraocular injection, but also after topical administration as eye drops. “… at least two compounds (prosthe6-12 and -15) appear to be devoid of adverse effects and restore sight by topical administration, which is linked to higher overall clinical success rate than systemic routes for neurological drugs, and to stronger patient adherence,” the investigators pointed out.

The prosthe6 technology is protected by patent and the researchers are now evaluating its safety and formulation to extend the duration of visual rehabilitation. The team is working with Eyelumina, a spin-off company in formation to secure investments that support translational development and future clinical trials.

“Turning this into a therapy is a long and laborious process,” says Gorostiza. “But the results show that there is a realistic possibility of restoring high-quality vision with drugs, non-invasively, reversibly and with a mechanism that is independent of the specific retinal disorder or genetic mutation to reach a majority of patients.”

If successful in humans, the drug-based approach would offer a widely accessible and affordable alternative to existing vision restoration technologies, especially relevant for patients with advanced retinal degeneration for whom no effective treatments currently exist.

In their paper the team further stated, “From a fundamental perspective, prosthe6 constitute new tools for ophthalmology to study the physiopathology of mGlu6 receptors and retinal circuits in vitro and in vivo and contribute to the medicinal chemistry of allosteric modulators. They also achieve the prediction that upstream targeted photopharmacology can deliver nearly native output signals, taking full advantage of the retinal circuit for high-quality vision restoration.”

The post See, Blind Mice: Consortium’s Drugs Restore Sight appeared first on GEN – Genetic Engineering and Biotechnology News.

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