In a new study published in Nature Communications titled, “Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks,” researchers from Flinders University in Adelaide have uncovered how hyperactive and dysregulated synaptic circuits emerge in the brain tissue of children impacted by Sanfilippo syndrome, a common form of childhood dementia.
In Australia, an estimated 1400 children currently live with childhood dementia, with hundreds of thousands of cases worldwide. Sanfilippo syndrome is a rare genetic condition that causes fatal brain damage. Children typically reach early developmental milestones before rapidly losing cognitive skills, speech, and mobility. Early symptoms often include hyperactivity and sleep disturbance.
Alterations in synaptic communication play key roles in neurodegenerative disease progression and cognitive decline. Yet few studies have explored how excitation and inhibition synaptic imbalances contribute to pediatric neurodegenerative disorders.
Cedric Bardy, PhD, professor and head of the Laboratory for Human Neurophysiology and Genetics at the South Australian Health, describes the study findings as “significant progress.”Chronic overactivity in the brain appears to be a fundamental mechanism contributing to cognitive deterioration in children with Sanfilippo syndrome.
Using human stem cell-derived cortical neurons and electrophysiology, the team demonstrated that excitatory synapses in the neurons of affected children become abnormally active during early brain development.
While these neurons initially developed and functioned normally, they became increasingly overactive over time. Brain cell networks showed bursts of intense, highly synchronized electrical activity as they matured, mirroring the hyperactivity and neurological symptoms seen in children with the condition.
“This hyperactivity offers a clear biological explanation for early behavioral changes, and it brings us closer to understanding the complex mechanisms contributing to childhood dementia,” said Bardy.
Results also demonstrated that these neurons are vulnerable to stress. When exposed to mild nutrient deprivation, excitatory synaptic abnormalities increased, suggesting that common illnesses or physiological stressors may accelerate neurological decline.
“Our research shows that disrupted synaptic communication is not simply a byproduct of degeneration. It is an early driver of the disease,” Bardy says.
Childhood Dementia Initiative CEO and founder, Megan Maack, is a co-author of the study and has been involved in guiding the project since its inception.
“This research is significant not just for Sanfilippo syndrome, but for the field of childhood dementia as a whole,” said Maack. “By identifying the precise cellular mechanisms driving the disease, we are moving towards a personalized medicine approach—the kind of targeted treatment strategy that has transformed outcomes for children with cancer.”
Researchers are now evaluating whether drugs that are already on the market for use in other conditions could be repurposed for childhood dementia. Bardy says the team has already demonstrated that these synaptic imbalances can be corrected with certain medications in the laboratory, indicating that they represent a genuine therapeutic target.
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Desalination plants in the Middle East are increasingly vulnerable
As the conflict in Iran has escalated, a crucial resource is under fire: the desalinization technology that supplies water in the region.
President Donald Trump has threatened to destroy “possibly all desalinization plants” in Iran if the Strait of Hormuz is not reopened. The impact on farming, industry, and—crucially—drinking in the Middle East could be severe. Find out why.
—Casey Crownhart
This story is part of MIT Technology Review Explains, our series untangling the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here.
AI is changing how small online sellers decide what to make
For small entrepreneurs, deciding what to sell and where to make it has traditionally been a slow, labor-intensive process. Now that work is increasingly being done by AI.
Tools like Alibaba’s Accio compress weeks of product research and supplier hunting into a single chat. Business owners and e-commerce experts say they’re making sourcing more accessible—and slashing the time from product idea to launch.
The gig workers who are training humanoid robots at home
When Zeus, a medical student in Nigeria, returns to his apartment from a long day at the hospital, he straps his iPhone to his forehead and records himself doing chores.
Zeus is a data recorder for Micro1, which sells the data he collects to robotics firms. As these companies race to build humanoids, videos from workers like Zeus have become the hottest new way to train them.
Micro1 has hired thousands of them in more than 50 countries, including India, Nigeria, and Argentina. The jobs pay well locally, but raise thorny questions around privacy and informed consent. The work can be challenging—and weird. Read the full story.
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This is our latest story to be turned into an MIT Technology Review Narrated podcast, which we’re publishing each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Anthropic’s new model found security problems in every OS and browser Claude Mythos has been heralded as a cybersecurity “reckoning.” (The Verge) + Anthrophic is limiting the rollout over hacking fears. (CNBC) + It’s also launching a project that lets Mythos flag vulnerabilities. (Gizmodo) + Apple, Google, and Microsoft have joined the initiative. (ZDNET)
2 Iranian hackers are targeting American critical infrastructure Their focus is on energy and water infrastructure.(Wired) + They’re targeting industrial control devices. (TechCrunch)
3 Google’s AI Overviews deliver millions of incorrect answers per hour Despite a 90% accuracy rate. (NYT $) + AI means the end of internet search as we’ve known it. (MIT Technology Review)
4 Elon Musk is trying to oust OpenAI CEO Sam Altman in a lawsuit As remedies for Altman allegedly defrauding him. (CNBC) + Musk wants any damages given to OpenAI’s nonprofit arm. (WSJ $)
5 ICE has admitted it’s using powerful spyware The tools that can intercept encrypted messages. (NPR) + Immigration agencies are also weaponizing AI videos. (MIT Technology Review)
6 Greece has joined the countries banning kids from social media Under-15s will be blocked from 2027. (Reuters) + Australia introduced the world’s first social media ban for children. (Guardian) + Indonesia recently rolled out the first one in Southeast Asia. (DW) + Experts say they’re a lazy fix. (CNBC)
7 Intel will help Elon Musk build his Terafab in Texas They aim to manufacture chips for AI projects. (Engadget) + Musk says it will be the largest-ever semiconductor factory. (Engadget) + Future AI chips could be built on glass. (MIT Technology Review)
8 TikTok is building a second billion-euro data center in Finland It’s moving data storage for European users. (Reuters) + Finland has become a magnet for data centers. (Bloomberg $) + But nobody wants one in their backyard. (MIT Technology Review)
9 Plans for Canada’s first “virtual gated community” have sparked a row The AI-powered surveillance system has divided neighbors. (Guardian) + Is the Pentagon allowed to surveil Americans with AI? (MIT Technology Review)
10 The high-tech engineering of the “space toilet” has been revealed Artemis II is the first mission to carry one around the world. (Vox)
Quote of the day
“This case has always been about Elon generating more power and more money for what he wants. His lawsuit remains nothing more than a harassment campaign that’s driven by ego, jealousy and a desire to slow down a competitor.”
—OpenAI criticizes Musk’s legal action in an X post.
One More Thing
USWDS
Inside the US government’s brilliantly boring websites
You may not notice it, but your experience on every US government website is carefully crafted.
Each site aligns an official web design and a custom typeface. They aim to make government websites not only good-looking but accessible and functional for all.
A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ Rejoice in the splendor of the “Earthset” image captured by Artemis II. + Meet the fearless cat chasing off bears. + This document vividly explains what makes the octopus so unique. + Revealed: the rhythmic secret that makes emo music so angsty.
Although immunoglobulin G (IgG) normally protects the body against pathogens, it can become problematic in many autoimmune diseases like lupus, rheumatoid arthritis, Graves’ disease, myasthenia gravis, and Sjögren’s disease.
“In these conditions, the immune system is creating defective IgGs—called autoantibodies—that are no longer fighting infections,” explained Eric Venker, MD, PharmD, CEO of Immunovant. “Instead, they are attacking a part of your normal functioning body and causing dysfunction.”
Leonard L. Dragone, MD, PhD Disease Area Leader Johnson & Johnson Innovative Medicine.
Historically, autoimmune conditions have been challenging to treat because therapies like steroids rely on broad immune suppression, noted Leonard L. Dragone, MD, PhD, disease area leader of autoantibody and rheumatology at Johnson & Johnson Innovative Medicine. These non-specific approaches are often inconsistently effective and lead to adverse side effects.
“For many autoimmune diseases, there is a need for more targeted strategies that address disease-causing autoantibodies directly, rather than broadly suppressing the immune system,” emphasized Dragone. Beginning in 1998, the U.S. Food and Drug Administration (FDA) approved infliximab, a tumor necrosis factor (TNF)-α inhibitor, for the treatment of Crohn’s disease. This marked the first approval of a monoclonal antibody for the treatment of a chronic condition. Since then, targeted therapies for autoimmune diseases have expanded to address cytokine signaling pathways (TNF-α, IL-6, IL-17, IL-23), Janus kinase (JAK–STAT) signaling, and immune cell surface markers (CD20).
Another such targeted strategy involves an emerging drug class called FcRn blockers, which are now showing considerable promise in the treatment of certain autoimmune diseases.
FcRn blockers, which typically consist of monoclonal antibodies or antibody fragments, work by blocking the function of a protein receptor called FcRn (neonatal Fc receptor). This prevents IgG recycling, thereby reducing IgG levels in the body.
FcRn maintains levels of IgG in circulation by preventing IgG degradation in the lysosomes of cells. However, FcRn drugs block this pathway.
Venker compares FcRn inhibitors to cholesterol-lowering drugs such as statins. “LDL is the disease-causing agent that healthcare providers target to prevent many cardiovascular diseases. Likewise, in the case of FcRn blockade, we are aiming to lower IgG. We believe that deeper IgG reduction may provide improved results.”
As of early 2026, the FDA has approved three FcRn inhibitors for the treatment of myasthenia gravis, a chronic autoimmune disorder affecting up to 100,000 people in the U.S. Efgartigimod (approved in 2021), rozanolixizumab-noli (approved in 2023), and nipocalimab-aahu (approved in 2025) all work by reducing pathogenic IgGs associated with the disease.
Myasthenia gravis results from harmful antibodies (anti-AChR or anti-MuSK) produced by the immune system that interfere with signaling in the neuromuscular junction.
“With FcRn blockers, it is exciting to know that there is now a targeted mechanism for patients around the world with autoimmune diseases caused by an IgG autoantibody,” said Venker.
Tackling Graves’ disease
In Graves’ disease, an IgG autoantibody called thyrotropin receptor antibody (TRAb), which targets the thyroid-stimulating hormone (TSH) receptor of the thyroid, is produced. The condition, which is the most common cause of hyperthyroidism, causes elevated heart rate, shakiness, irritability, muscle weakness, and weight loss.
“TRAb is an IgG antibody, but it is a badly behaving one that is basically hijacking the thyroid system,” noted Venker. “It doesn’t serve any purpose that is normal at all.”
Mark A. Lupo, MD Founder and Medical Director Thyroid & Endocrine Center of Florida
Unfortunately, the toolkit for treating Graves’ disease hasn’t changed much since 1950, when the FDA approved the drug methimazole, said Mark A. Lupo, MD, founder and medical director of the Thyroid & Endocrine Center of Florida.
Methimazole is an anti-thyroid drug that slows down the production of thyroid hormones. Although Graves’ patients benefit from anti-thyroid drugs, Lupo estimates a 50% relapse rate within two years of discontinuing these drugs.
Other options for treating Graves’ disease include surgical removal of the thyroid or the use of radioactive iodine to induce destruction of the thyroid gland. However, these approaches result in permanent hypothyroidism, and patients typically require lifelong thyroid hormone replacement after treatment.
Because TRAb is an IgG, FcRn drugs represent a potential autoimmune solution for Graves’ disease. Like all FcRn blockers, they may work by decreasing TRAb recycling and lowering TRAb levels.
Lupo highlights Immunovant’s recent proof-of-concept study of an FcRn inhibitor for Graves’ disease, the first such study for the condition. “Despite the small number of patients (around 25), the results from this study suggest a potential, durable remission six months off treatment,” said Lupo.
While study participants experienced an increase in total IgG levels following treatment, TRAb levels remained low over a six-month period. The thyroid also decreased in size. “To see TRAb levels down six months off the study drug caught the attention of the endocrine thyroid community,” noted Lupo.
“What was unexpected was that TRAb, the disease-causing antibody, stayed down for many months after stopping the investigational therapy,” added Venker.
“I think we are overdue for a new option in Graves’ disease that could help break some of these methimazole cycles and potentially address not the innocent thyroid gland but the underlying immune system issues,” concluded Lupo.
But are they safe?
Venker recalls that safety was an initial concern with FcRn inhibition. After all, these drugs work by reducing IgG, an essential part of the immune system. “Any time you are using an autoimmune drug that potentially suppresses your immune system, you have to think about going too far. Am I going to cause an infection or weaken the immune system?
“So far, this investigational drug has demonstrated a safety profile we expected, and appears positive,” noted Venker. “That makes sense mostly because FcRn blockade is pretty targeted.”
“Although there are no head-to-head comparative safety trials yet, most clinicians and principal investigators view FcRn blockers as relatively safe,” added Lupo. “There are FcRn blockers on the market, and they have demonstrated a good safety record in patients.” The most common side effect tends to involve injection site reactions with either intravenous or subcutaneous delivery.
Preventing fetal exposure
During pregnancy, maternal antibodies—called alloantibodies—can cross the placenta and attack the organs and tissues of the fetus, explained Dragone.
A distinguishing feature of Johnson & Johnson’s nipocalimab is its pH-independent binding to FcRn. This allows it to bind with high affinity in the placenta, a low-pH environment.
The drug is currently showing potential in the treatment of two alloimmune diseases of pregnancy: hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT), said Dragone. These conditions can arise during alloimmunized pregnancies, when the pregnant person’s immune system forms alloantibodies against fetal red blood cells (HDFN) and/or fetal platelets (FNAIT). Importantly, published data on nipocalimab suggest minimal transfer of the drug to the fetus or infant. “Therapies like nipocalimab offer a blueprint for how precision medicine can expand to include pregnant people, a population that has historically been excluded from drug development,” noted Dragone. “Our approach with nipocalimab has the potential to change how we think about treating autoantibody-driven diseases in people of childbearing age.”
Nipocalimab (IMAAVY®) and other FcRn blockers bind to FcRn receptors and reduce levels of both normal and harmful IgG antibodies.
The FDA has granted a fast track designation to nipocalimab for both FNAIT and HDFN, and Phase III studies are underway to further investigate the drug in both diseases.
Expanding indications
“There are probably 20 trials out there for FcRn blockers, and many are likely to work,” noted Venker. “There are a ton of potential new indications under investigation, including rare diseases that have been ignored historically.”
He notes that Immunovant’s pipeline alone includes potential indications in endocrinology (Graves’ disease), rheumatology (rheumatoid arthritis, Sjögren’s disease, and cutaneous lupus erythematosus), and neurology (myasthenia gravis and chronic inflammatory demyelinating polyneuropathy).
Venker stresses that no FDA-approved solutions exist for Sjögren’s disease, which affects as many as four million Americans. The condition causes severe dry eyes and mouth, fatigue, and joint and muscle pain. Immunovant and Johnson & Johnson are conducting clinical trials to evaluate FcRn blockers for the disease.
Hani Houshyar, PhD Strategy Team Lead argenx
Meanwhile, argenx’s FcRn inhibitor efgartigimod has been used in 19,000 people worldwide for myasthenia gravis and other autoimmune conditions, said Hani Houshyar, PhD, FcRn asset strategy lead for argenx.
“However, we believe myasthenia gravis is just the beginning,” she said. As of 2026, the company has active clinical trials to test the drug’s effectiveness in additional autoimmune diseases with high unmet medical need, like myositis, Sjögren’s disease, ocular myasthenia gravis, systemic sclerosis, Graves’ disease, and autoimmune encephalitis.
UCB’s rozanolixizumab was the first FcRn blocker to be approved for the treatment of generalized myasthenia gravis in adults who are positive for anti-AChR or anti-MuSK antibodies, who together account for approximately 90% of cases, said Omar Sinno, MD, UCB’s U.S. medical strategy lead of rare disease. So far, the drug has been approved in the U.S., Canada, the EU, Australia, Switzerland, China, Turkey, and Korea.
Omar Sinno, MD Medical Strategy Lead, UCB
Rozanolixizumab is administered via a convenient subcutaneous infusion rather than intravenously. The company’s long-term studies demonstrate robust IgG reductions (up to 75%) with sustained benefit across multiple treatment cycles. UCB is also investigating rozanolixizumab as a potential treatment for a rare autoimmune condition called myelin oligodendrocyte glycoprotein antibody-associated disease.
Finally, Johnson & Johnson’s nipocalimab is in mid-to-late-stage studies for Sjögren’s disease, lupus, warm autoimmune hemolytic anemia, and chronic inflammatory demyelinating polyneuropathy.
Drugs in development
Viridian Therapeutics is currently investigating two FcRn inhibitors, VRDN-006 and VRDN-008, said Steve Mahoney, president and CEO. Both candidates are designed as subcutaneous products that can be conveniently self-administered by the patient.
Steve Mahoney President and CEO Viridian Therapeutics
VRDN-006 is an Fc fragment in Phase I trials, while VRDN-008 is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression. Mahoney notes that VRDN-008 showed a longer half-life and more sustained IgG reduction than efgartigimod in a high-dose, head-to-head study in non-human primates.
Clinical trial results of VRDN-008 in healthy volunteers are expected later in 2026. “What we believe differentiates VRDN-008 from other FcRn inhibitors is a longer half-life, which has the potential to support less frequent dosing for patients to enhance convenience,” said Mahoney.
Although three FcRn blockers are currently FDA-approved to treat myasthenia gravis in the U.S., Venker notes that Immunovant is continuing to investigate the condition with the company’s follow-on FcRn candidate, imeroprubart (IMVT-1402).
In Immunovant’s proof-of-concept study for Graves’ disease, TRAb stayed low even six months after the investigational treatment was discontinued. But how long will this effect last? “We don’t know that yet because our randomized trials with IMVT-1402 are ongoing,” Venker said. “However, Graves’ disease has given us the first hint that FcRn drugs may be able to put certain autoimmune conditions into permanent remission.”
Viridian’s VRDN-006 (top) is an Fc fragment, whereas VRDN-008 (bottom) is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression.
“A key question for autoimmune disease, the holy grail, so to speak, is whether we can reset the immune system so the person can function normally without medication for the rest of their lives,” he added.
Finally, argenx is developing ARGX-213, a next-generation FcRn inhibitor engineered to extend half-life and sustain IgG reduction.
“Looking ahead, FcRn inhibition represents an increasingly important approach across IgG-driven disease,” noted Sinno. “By selectively reducing pathogenic IgG, these agents enable more targeted autoimmune care. And as clinical experience with FcRn inhibition grows, treatment paradigms may shift toward earlier intervention.”
Tiffany Yesavage, PhD is a freelance writer from Denver, Colorado.
