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April 6, 2026

FcRn Inhibition in Autoimmune Disease

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.

Immunovant — 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.

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 illustration — 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.

The post FcRn Inhibition in Autoimmune Disease appeared first on Inside Precision Medicine.

April 6, 2026

STAT+: Health insurers score major win with higher 2027 Medicare Advantage rates

Companies that sell Medicare Advantage plans will receive a 2.5% pay bump on average in 2027, up significantly from what was proposed and a win for an industry that has experienced higher medical costs and has opposed nearly all reforms to the lucrative taxpayer-financed program.

More importantly, the Trump administration scrapped a proposal that would have used more updated data in the payment process, ensuring that Medicare Advantage insurers retain billions of dollars.

The finalized rate is estimated to add $13 billion in revenue next year for insurers, according to the Centers for Medicare and Medicaid Services. During trading after the markets closed, the stock prices of UnitedHealth Group, Humana, and CVS Health each climbed by more than 8%. Those companies are the three largest Medicare Advantage insurers, and together cover almost 60% of all people enrolled in the program.

Continue to STAT+ to read the full story…

April 6, 2026

CRISPR at 25: The Past, Present, and Future of Genome Editing

Panelists:

Rodolphe Barrangou, PhD

North Carolina State University

Broadcast Date: Monday, May 4, 2026

Time: 09:00 PDT, 12:00 EDT, 16:00 GMT

It has been almost 25 years since the acronym “CRISPR” was first coined. Since then, CRISPR has become a household word, a star of books and films, and a Nobel Prize–winning discovery. This powerful and disruptive genome editing technology has transformed countless fields, including gene therapy, xenotransplantation, de-extinction and agbiotech. Researchers continue to build on the CRISPR chassis, devising new platforms for bespoke genome editing. But major questions remain around clinical safety, commercial development, ethical deployment, and regulatory oversight.

In the first of a new series of GEN Keynote Webinars, Professor Rodolphe Barrangou, PhD (North Carolina State; EIC, The CRISPR Journal) offers a front-row perspective of the CRISPR revolution, the seminal advances, clinical highlights, and rising applications. Almost two decades ago, Barrangou provided the first experimental demonstration of the functional role of CRISPR. With numerous advisory and entrepreneurial activities in the gene editing space, Barrangou is the ideal guide to discuss CRISPR’s progress in the clinic; the state of the CRISPR toolbox; and the regulatory roadblocks and ethical challenges that will shape the application of CRISPR in agbiotech, germline editing, and other arenas.

Registration for this GEN Keynote Webinar is free. Following this live presentation, Dr. Barrangou will answer audience questions.

Produced with support from:

The post CRISPR at 25: The Past, Present, and Future of Genome Editing appeared first on GEN – Genetic Engineering and Biotechnology News.

April 6, 2026

STAT+: Pharma companies and patient groups seek to exempt orphan drugs from Colorado pricing limits

For the second time in two years, a bill is moving through the Colorado legislature that would exempt orphan drugs, which are used to treat rare diseases, from pricing caps that might be pursued by the state’s Prescription Drug Affordability Board — a panel whose work is being closely watched elsewhere in the country.

The effort reflects concerns that patients may lose access to these drugs if pharmaceutical companies halt sales of such treatments in the state. But opponents argue exemptions would unnecessarily extend to numerous big-selling medicines for common conditions that — thanks to regulatory endorsements — also happen to have an orphan designation.

As a result, consumer advocates complain the maneuver would only increase the risk that countless patients could have trouble paying for a wide variety of medicines. They further argue that the legislation would preserve profits for drug companies at the expense of the state government — and its taxpayers — as it tries to cope with budgetary strains.

Continue to STAT+ to read the full story…

April 6, 2026

Igyxos Biotherapeutics is Enhancing Hormone Activity to Treat Infertility

Since the first in vitro fertilization (IVF) baby was born in 1978, the options for couples or individuals struggling with infertility have improved exponentially. However, the core methods that make up this process are still fairly crude and associated with significant discomfort and side effects. This is something that reproductive endocrinologist Marie-Christine Maurel, PhD, chief scientific officer (CSO) and founder of Igyxos Biotherapeutics, is hoping to improve with the company’s first‑in‑class antibody treatment for infertility.

The antibody treatment—IGX12—amplifies the body’s own follicle-stimulating hormone (FSH) signal in both women and men, potentially improving production of both sperm and eggs with fewer injections than IVF and more physiological control.

Maurel has a doctorate in reproductive physiology from Pierre & Marie Curie University in Paris and worked as a post-doctoral fellow at the Pasteur Institute in Paris. The idea for the infertility treatment, which achieved promising Phase I results at the end of last year, originated from work at Maurel’s first biotech firm ReproPharm, which she co-founded in 2009 after winning a French “national competition for the creation of innovative companies.”

Maurel previously worked at the National Institute of Agronomic Research (INRA) near Paris for more than 25 years. Her group studied how gonadotropins affect fertility in animals and developed monoclonal antibodies that impact the activity of these reproductive hormones. ReproPharm initially used this research to improve fertility in farm animals, but when the team realized the same ideas could be applied to human infertility, the initial company was split into ReproPharm Vet and Igyxos in 2017 to focus on animal and human fertility problems, respectively. Alongside serving as CSO at Igyxos, Maurel remains president and CEO of ReproPharm Vet.

Maurel discussed her inspirations, research, and motivations for founding both companies with Inside Precision Medicine’s senior editor, Helen Albert, and outlined why Igyxos’s antibody could be so important if it achieves market authorization.

Q: What inspired you to become a scientist?

Maurel: When I was younger, I was passionate about science, and biology in particular. In my teens, I hesitated between choosing to study medicine or biological research. Finally, I chose biological research, but remained very interested in biomedicine. Currently, I mix both topics because we are developing a new medicine to treat infertility problems in humans, so it’s a mix of research and medicine. I still enjoy scientific research, so I don’t regret my decision.

Q: You worked in academia for a long time before you decided to make the move into industry. What inspired you to do that?

Maurel: In nature, there are lots of things that occur. You just have to discover them and know how to ask the right questions to understand how they work. Penicillin is an extraordinary example. And here it’s the same thing. We were doing experiments with sheep and goats. When we discovered that the ewes or does that secreted potentiating antibodies were hyper prolific and had high numbers of offspring, we wondered why. Normally, antibodies block the activity of a hormone and never enhance it. But in this case, we discovered that these particular antibodies were able to potentiate the activity of reproductive hormones. It was a marvelous result because it meant [that] it was possible to avoid the use of hormone treatment in animals. When my team and I discovered the existence of these potentiating antibodies, I quickly assessed their potential for application in both human and animal health. I wanted to develop and translate the research. The fact that there are potentiating antibodies for FSH is extraordinary, because antibodies are normally always inhibitory. I wanted to develop a potentiating antibody so we could have much more effective treatments for infertility. I also won a national competition for the creation of innovative companies, which helped with founding ReproPharm. It was a wonderful adventure to create a new biotech with our innovation.

Q: What did you learn from the experience of founding ReproPharm?

Maurel: I learned a lot of things. It was a human experience. I met a lot of people in medicine and industry who were very important for the development of the company and myself as well. These people helped me to build and to progress the company. Building a good network was important for me when I went into industry. I would also advise this for young people who want to create a biotech company. Meeting good people helps enormously!

Q: What made you decide to split ReproPharm into the two spinout companies, ReproPharm Vet and Igyxos Biotherapeutics?

Maurel: My research group was based at INRA initially. It’s a French academic research center focused on animal reproduction. We started with an animal reproduction problem linked to breeding ovine and caprine species, but early on, we tried our innovation on human hormones because we thought it could be an excellent approach to treat infertility problems in women. We developed an antibody against human FSH to see if we could enhance the activity of human FSH and in animal species. We got some money to carry out the first experiments and had very good results. We then decided to develop this innovation in human health, but needed more funds to develop it further. All our existing investors told us that they were unwilling to take the risk of investing in a company developing both veterinary and human medicine. It was impossible for them because it was not separated, so we decided to split the first company into two independent companies in 2017.

Q: Did any of your experiences at ReproPharm help you to do things better at Igyxos?

Maurel: First, I can say that at Igyxos, from the experience with ReproPharm, I wanted to do as much research and development on IGX12 as possible using our own funds, and license the therapy as late as possible because that gives us more freedom to develop it as we want to. I think it is necessary to be independent as long as possible for this reason.

Also, during the founding and development of ReproPharm, we developed a lot of animal models, which are very useful now to develop IGX12 for treating human infertility, both in men and women. So it was a very strong basis for Igyxos. All these animal models we developed at ReproPharm were important for developing IGX12 and getting it to clinical trials.

Q: Can you tell me a bit more about what you’re trying to achieve at Igyxos?

Maurel: FSH is exactly the same hormone in men and women. It has different target cells, but the molecule is the same. So one potentiating antibody could act on FSH either in men or women. It’s exactly the same mechanism of action, so we can develop the first treatment in men with oligozoospermia, for example.

We also want to develop a new and innovative treatment for women with infertility, which could be more efficient than current treatments that are burdensome and costly. Now it’s necessary to repeat the same hormone treatment four or five times to have a baby with a 50% chance of success. We think that it will not be necessary to repeat our treatment because we have a lot of proof of concept in animals. We have shown we can get better gametogenesis with better quality of ovulation than other methods.

Q: You reported Phase I results in December 2025. Were you happy with the findings?

Maurel: Yes, it was totally successful. We got very nice results. No adverse events, and we have some first efficacy results, so we can start Phase II trials, but we need to raise money first.

The trial results have helped to interest investors, and we are now in contact with several funds. If the fundraising is successful, we hope to be able to start Phase II trials soon.

Q: You mentioned that IGX12, if approved, would be the first such treatment for men with common fertility issues like oligozoospermia. Why have more treatments not been developed for men before?

Maurel: The problem of male infertility was not considered for a long, long time, perhaps because of cultural issues. Now there is a huge problem with infertility in men because sperm counts are decreasing. Numbers decreased from around 100 million per mL to 50 million per mL between 1973 and 2018. So this treatment is very necessary!

Q: Do you think that if your treatment is successful, it could make IVF more accessible?

Maurel: Yes, I think that it would allow a reduction in both time and economic cost, because as I said previously, the treatment will be more efficient, so no need to repeat it. We developed the concept that the antibody could act on the endogenous FSH. So, using our approach, it would not be necessary for women to inject FSH, because the antibody is able to boost the woman’s own FSH. In the animal health domain, we use the antibody only. We never inject endogenous hormones, so it’s very clean. In humans we will also only inject the antibody. We never inject FSH. So it’s a single injection per month. If we succeed, it’s a very big market and a very nice treatment for a lot of people.

Q: Could IGX12 make fertility treatment more targeted for specific people or certain population groups?

Maurel: Yes, for example, men with oligozoospermia. That means the sperm count is too low for natural conception. If it’s a very low level, it’s not even possible to do IVF. So we will target this category of men. In women, we will target those who don’t have a good predicted result with IVF, for example, if they have a low follicular count. So we plan to target these two populations, which have few chances to succeed at having children with current treatments.

Q: What are your future plans for Igyxos and ReproPharm Vet?

Maurel: For Igyxos, the current priority is to raise funds to start Phase II clinical trials, both in men and women. For ReproPharm Vet, the objective is to conclude an ongoing collaboration with a big veterinary and pharma partner.

Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.

The post Igyxos Biotherapeutics is Enhancing Hormone Activity to Treat Infertility appeared first on Inside Precision Medicine.

April 6, 2026

Immunotherapy Enhanced by Restoring Mitochondrial Function in Dendritic Cells

In a new study published in Science titled, “Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity,” researchers from St. Jude Children’s Research Hospital have uncovered a new metabolic mechanism for how tumors disable immune “gatekeeper” cells that initiate response in the presence of cancer. The results offer a new path to improve immunotherapy.

Dendritic cells alert and activate tumor-killing immune cells as a critical part of anticancer immune response. The authors found that tumors reduce dendritic cell function by minimizing mitochondrial fitness to prevent anticancer immune response. Correspondingly, boosting mitochondrial function in dendritic cells enhances antitumor immune activity and strengthens the efficacy of existing immunotherapies.

Within the nutrient-sparse tumor microenvironment, dendritic cells progressively lose mitochondrial activity, which drives cell dysfunction and weakens immune defenses against cancer. When dendritic cells with high mitochondrial activity were introduced into tumors in preclinical mouse models, results showed that immunogenic activity was restored while improving tumor control.

“We found that tumors reprogram mitochondrial metabolism in dendritic cells, reducing their ability to activate the immune system against cancer,” said Hongbo Chi, PhD, St. Jude Department of Immunology chair and corresponding author of the study. “By enhancing mitochondrial function, we could restore dendritic cell activity and rescue antitumor immunity.”

Immunotherapies for cancer, such as immune checkpoint blockade, have greatly improved care for many malignancies, but have not been successful in all cancers. To determine whether these findings could improve immunotherapy effectiveness in tumor-bearing mice, the authors evaluated the administered dendritic cells with high mitochondrial activity in combination with immune checkpoint blockade.

“We saw the most pronounced therapeutic effect in mice treated with the combination of dendritic cells that had high mitochondrial activity and immune checkpoint blockade,” said co-first author Zhiyuan You, PhD, researcher at St. Jude Department of Immunology. “Those combinations synergistically slowed or stopped tumor growth and extended survival far more than either treatment alone.”

To test long-term effects, the researchers exposed combination therapy treated mice to a new tumor after a few months. New tumor growth stopped for these mice, indicating durable, long-term immune memory.

To better understand the relationship between mitochondrial function and dendritic cells, the researchers examined metabolic pathways affected by the tumor microenvironment. They identified a signaling axis composed of two proteins, OPA1 and NRF1, that regulate communication between mitochondria and the nucleus. Expression was greatly downregulated in dendritic cells during tumor progression and acted as a metabolic switch to shut down dendritic cell immunogenic activity.

“We’re seeing a direct regulation of dendritic cells by the tumor microenvironment,” said co-first author Jiyeon Kim, PhD, researcher at St. Jude Department of Immunology. “We have characterized how that results in mitochondrial reprogramming of dendritic cells to benefit cancer, giving us new opportunities to reverse the process.”

The study’s mechanistic insights enable new directions to rewire dendritic cell function and enhance cancer treatments.

“These findings reinforce the central role of dendritic cells in cancer immunity,” Chi said. “By exploring their mitochondrial function in the tumor microenvironment, we have provided a proof-of-principle of how we may be able to improve the next generation of immunotherapies.”

The post Immunotherapy Enhanced by Restoring Mitochondrial Function in Dendritic Cells appeared first on GEN – Genetic Engineering and Biotechnology News.

April 6, 2026

Low-Cost, Single Sample Blood Test Detects Different Cancers, Liver Disorders, and Other Diseases

UCLA scientists have developed a simple and cost-effective blood test that, in early studies in more than 1,000 people, showed promise in detecting multiple cancers, various liver conditions, and organ abnormalities simultaneously.

The new method, called MethylScan, works by analyzing cell-free DNA (cfDNA), tiny fragments of genetic material released into the blood when cells die. Because cells from every organ shed DNA into the bloodstream, cfDNA carries molecular signals that reflect what is happening throughout the body.

The researchers say MethylScan could represent a powerful and more affordable approach to early disease detection and comprehensive health monitoring. “Early detection is crucial,” said research lead Jasmine Zhou, PhD, a professor of pathology and laboratory medicine and investigator at the UCLA Health Jonsson Comprehensive Cancer Center. “Survival rates are far higher when cancers are caught before they spread. If you detect cancer at stage one, outcomes are dramatically better than at stage four.” Zhou is senior author of the team’s published paper in PNAS, titled “Toward the simultaneous detection of multiple diseases with a highly cost-effective cell-free DNA methylome test.”

“When cells die, they do not simply vanish; they leave behind molecular traces, including cell-free DNA (cfDNA) in the blood stream,” the authors wrote. “cfDNA is a mixture of DNA fragments released from various organs, offering valuable insights into the health of these organs.” Zhou added, “Every day, 50 to 70 billion cells in our body die. They don’t just disappear, their DNA goes into the bloodstream. That means we already have information from all our organs circulating in the blood.”

The idea of using blood to detect cancer, sometimes called a liquid biopsy, isn’t new. Some tests already look for mutations in tumor DNA to screen for certain cancers. But those tests often focus on a limited number of genetic changes and can be expensive, in part because they require deep sequencing to detect faint tumor signals.

Instead of searching for mutations, the UCLA team examined DNA methylation, chemical tags attached to DNA that help regulate gene activity. Methylation patterns differ by tissue type and can change when cells become cancerous or diseased. “Unlike an individual’s genome, which remains largely stable across tissues and over time (except for rare somatic mutations), the DNA methylome is tissue-specific and dynamically changes with the tissue’s disease status,” the team continued.

“DNA methylation reflects the health status of a tissue,” said co-corresponding author Wenyuan Li, PhD, a professor of pathology and laboratory medicine at UCLA and co-corresponding author of the study. “It’s a very informative signal.”

The challenge is that most cell-free DNA in the bloodstream doesn’t come from tumors or injured organs. About 80% to 90% originates from normal blood cells. That creates background noise, making it difficult and costly to detect the relatively rare fragments that might signal early cancer. “A major challenge in using the cfDNA methylome for disease detection is the high cost of sequencing,” the team stated. “In healthy individuals, about 85% of cfDNA originates from blood cells, creating substantial background noise that can obscure cfDNA from tumors or diseased organs.” And as the authors further pointed out, “Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci.”

For their newly reported research the team built on past work to develop a technique to remove much of the background DNA before sequencing. Using specialized enzymes, they selectively cut away unmethylated DNA fragments that largely come from blood cells. By designing a genome-wide hybridization panel, the captured DNA fragments are enriched for methylated DNA from solid organs, including those that are potentially diseased. “The MethylScan method is a targeted methylation assay that combines Methylation-Sensitive Restriction Enzymes (MSRE) digestion with a custom panel to enrich hypermethylated cfDNA from tissues beyond blood, enabling cost-effective detection of multiple diseases,” they wrote.

By removing the noise, the researchers say they can dramatically reduce the amount of sequencing needed, lowering costs while maintaining sensitivity. Achieving an effective sequencing depth of 300× per sample requires only 5 Gb of data, which would cost less than $20 if the price per gigabase is under $4.

To test the accuracy of MethylScan, the researchers analyzed blood samples from 1,061 people, including patients with liver, lung, ovarian and stomach cancers; individuals with liver diseases such as hepatitis B, hepatitis C, alcohol-related liver disease, and metabolic-associated liver disease; people with benign lung nodules; and healthy participants. Machine learning algorithms were then applied to analyze the complex methylation data.

For multi-cancer detection, the test achieved a high level of overall accuracy. At a specificity of 98%, meaning few false positives, it detected about 63% of cancers across all stages and roughly 55% of early-stage cancers. The test also performed well in liver cancer surveillance among high-risk individuals, including those with liver cirrhosis or HBV, detecting nearly 80% of cases at a specificity of just over 90%, meaning a less than 10% false positive rate.

Beyond simply detecting cancer, the methylation patterns helped identify where in the body a signal was coming from, known as the tissue of origin. “Being able to trace signals back to their source is important because a positive blood test needs to be followed by imaging or other diagnostic procedures directed at the right organ,” said Li.

MethylScan can work like a health radar for the body. By reading DNA signals in the blood, it can tell when specific organs, such as the liver or lungs, are under stress or damaged, even without knowing the disease in advance. The researchers also showed that the blood test could distinguish between different types of liver disease, including viral hepatitis and metabolic-associated liver disease. It correctly classified about 85% of patients, suggesting blood-based DNA testing could reduce the need for invasive liver biopsies.

Although larger prospective trials will be needed to confirm its performance in real-world screening, Zhou said the work represents an important step toward a single, affordable blood assay that can detect a broad spectrum of diseases earlier and more comprehensively than current methods allow.

“Because cfDNA in blood originates from multiple organs, and ‍MethylScan captures a broad spectrum of robust hypermethylation markers, this assay has the potential to detect a variety of diseases, provided that appropriate training cohorts are available,” the investigators stated. “This versatile approach enables affordable, wide-ranging cfDNA tests that can identify various health conditions simultaneously, with the potential to transform early disease detection and health monitoring across diverse clinical settings.

Zhou added, “This study demonstrates that blood-based methylation profiling can deliver clinically meaningful information across multiple diseases. It’s an exciting advancement that brings us closer to realizing the dream of a single assay for universal disease detection.”

The post Low-Cost, Single Sample Blood Test Detects Different Cancers, Liver Disorders, and Other Diseases appeared first on GEN – Genetic Engineering and Biotechnology News.

April 6, 2026

In Conversation with Haijiao Liu, PhD

As a postdoctoral researcher at the University of Pennsylvania, Haijiao Liu, PhD, helped advance tumor-on-a-chip technology, a feat of bioengineering that mimics the microenvironment of malignant human tumors. Led by Dan Dongeun Huh, PhD, a Penn Engineering professor and trailblazer of organ-on-a-chip technology, Liu and his team explanted lung adenocarcinoma tumors onto the transparent chips to test their perfusion with chimeric antigen receptor (CAR) T cells. Their findings were published in October in Nature Biotechnology, with Liu as first author.

Now on paternity leave in Toronto, Liu spoke with Lindsey Leake about the implications of this work, the challenges inherent to tumor-on-a-chip studies, and his plans to launch a lab of his own this fall.

Q: Walk me through the creation of the tumor-on-a-chip. What went into its design?

Haijiao Liu: It’s essentially inspired by the need for alternative tumor models. This is speaking to the traditionally used animal tumor models and some existing in vitro tumor models, especially for the study of immunotherapies.

For example, when I started at Penn around 2018, Penn Medicine was pioneering this immunotherapy called CAR T-cell therapy, which is basically aiming to harness the patient’s own immune system, specifically the patient’s own T cells, to help fight the cancer. Penn Medicine was demonstrating huge clinical success using this CAR T therapy to treat blood cancers, such as leukemias and lymphomas. In a huge contrast to this, the solid cancer arena has seen a limited response from this new immunotherapy. So there’s this great need to study why this has not been successful, and that comes down to the consensus that the solid tumor has this really complex microenvironment.

In the category called tumor-on-a-chip, people try to control the cultural environment, the biochemical and biophysical environment of tumor cell cultures. We can use this for simple drug testing—see how the tumor growth will be affected or how effectively they can be killed. However, these existing tumor-on-chip or in vitro tumor models are still very simple. They don’t usually recreate or reproduce the complex structure of the human solid tumors that I described, like where they often include complex vessel networks.

I took the lead to address the need and the challenges of reproducing and then investigating, or probing, the dynamic interactions between those CAR T cells and human solid tumors entirely in vitro.

Q: How does the vascularization work on the chip?

Liu: It took several years to start, from the idea of building this more advanced tumor-on-a-chip technology toward proving it’s actually useful. I started by focusing on this one aspect, which is the CAR T-cell trafficking and their functions after they traffic to fight the tumors, and that will involve the recreation of the structural interface between the tumor and this complex vascular network that’s present in human tumors.

I was inspired by in vivo tumor transplantation, where traditionally, people take human tumors and then transplant them in a bulk, intact format into animal models. So my idea was, if we want to focus more on the human biology, if we want to engineer this entirely in vitro, how about we design a vascular bedding, like a miniature living model?

We basically took advantage of the self-assembly capability of human-sourced endothelial cells, combined with certain stromal fibroblasts, or stromal cells. With a bit of optimization, engineering, tweaking, then we can allow them to form capillary-like vascular networks in our engineered models.

Q: What are the advantages of recreating the tumor microenvironment in this way? That is, is the Petri dish becoming obsolete in cancer research?

Liu: The unique advantage of this way of engineering is to have a higher level of control over the structures of the tissue-tissue interface that we can build. For example, we can engineer different culture chambers. We can engineer different access windows with this model. That allows us to construct, step by step, the vascular bedding and then the tumor transplantation. Also, by forming these perfusable vessels—by the way, we can provide the infusion and flow of the CAR T cells, just like they are infused and flow in the patient—that gives us the leverage to reconstruct, probe, and then control these tissue functions in a highly precise manner.

Q: How did you and your colleagues at Penn explore CAR T-cell activity on the chip?

Liu: We first used different functional assays, like immunostaining and ELISA (enzyme-linked immunosorbent assay) assays, to characterize how the CAR T cells are doing and how they are interacting with the tumors in our engineered model. Then we disassembled this engineered tissue to extract all the cells for flow cytometry, to further characterize their functional phenotypes.

With the help of our collaborators and other people in the lab, I took advantage of this engineered model of vascular tumors interacting with CAR T cells for multi-omics analysis. For example, I was able to extract all the cells and send them for single-cell RNA seq[uencing]. We were able to look at the gene expressions of each individual cell from all the cell types that we included in this model. In this way, we have almost like a superpower to probe and read into how each cell—including the CAR Ts and tumors and the vessels—how they are responding and interacting with each other at the molecular gene levels. This is so powerful that it helped me to discover novel interactions between these parties and also new druggable targets.

The message is that through the development of this more advanced tumor-on-a-chip technology—combined with advanced multi-omics analytics and advanced computational analysis—we were able to provide this powerful in vitro technology to apply to accelerate the development of cell therapies, such as the CAR T immunotherapies for cancer, but also other complex diseases.

Q: What are the overall implications of this latest research?

Liu: With a growing understanding of human biology at the cellular and tissue levels, I think we’re seeing that our ability to engineer and design biological systems is also growing. More than ever, we have these advances in the ability to precisely construct, investigate, and then eventually control very complex tissue functions, and even organ functions. For example, our demonstrated tumor-on-a-chip technology is like presenting a miniature sandbox; we can literally see and predict the battlefield of CAR T therapy in cancer.

If we combine these advanced engineering technologies with emerging technologies in spatial multi-omics and the unprecedented productivity of the AI revolution, we will be able to accelerate the understanding of more complex human biology and extract more biological insights, and then apply that to accelerate the development of safer and more efficacious drugs and therapies, such as immunotherapies in cancer.

Q: What are the limitations of organ-on-chip technology that need to be overcome?

Liu: I think there are challenges on two fronts. The first limitation is the lack of complexity. We’re claiming that what we just published is a sufficiently complex system for us to deeply probe and understand the dynamics of CAR T tumor interactions. Still, if we’re speaking next level of translational power or potential, then we need to pursue a higher complexity that incorporates the missing but critical components from in vivo.

The other side of the coin is that if you make this engineered model more complex, you make it more challenging to reproduce or to scale up or to translate to other labs. But also, that points to an opportunity and growing room for translation, to standardize every single step, from the construction to the analysis of these engineered models, and to automate these processes as much as possible.

Q: What do you envision for your new lab?

Liu: I have a lot of things I want to do. I’m eager to establish my own team. The overarching and the unifying theme of the new lab will be to develop the next generation of in vitro complex tissue models, or I call it assembloid tissue models. Assembloid basically means there’s a stem cell-based, three-dimensional complex tissue model that intentionally incorporates different cell types, to emulate the critical tissue-tissue interactions that determine the tissue- and organ-level functions. I still need to make a big decision where the lab could be; it could be in Canada and it could also be in China.

Q: What impact might tumors-on-a-chip have on the future of precision medicine?

Liu: It’s attracting a lot of attention from biologists and clinicians who are heavily focused on using the traditional tissue models—animal models, for example, or the simple dish cultures—for their studies of interest. So the biggest impact I can foresee with our technology is that now it’s more mature. I can see it being gradually, and maybe quickly, adapted into more traditional biological labs, to help them dissect the complex biological questions they’re asking, or to accelerate the evaluation of the exciting new drugs or therapies they’re developing. Overall, I can see that accelerate this development pipeline of new drugs and therapies in precision medicine.

Lindsey Leake is an award-winning, independent health reporter based outside Washington, D.C. She spent 15 years as a staff journalist at outlets including Fortune, the USA TODAY Network and Sinclair Broadcast Group. She holds an MA in Science Writing from Johns Hopkins University, an MA in Journalism and Digital Storytelling from American University and a BA from Princeton University.

The post In Conversation with Haijiao Liu, PhD appeared first on Inside Precision Medicine.

April 6, 2026

RNA Toxicity Is a Driver of Heart Disease in Muscular Dystrophy

Researchers at Baylor College of Medicine have identified a mechanism driving progressive heart disease in people with myotonic dystrophy type 1 (DM1) that operates independently of genetic repeat expansion, providing new evidence of how cardiac damage develops and when it may be reversible. The study, published in the Journal of Clinical Investigation Insight, shows that sustained expression of expanded CUG (CUGexp) repeat RNA drives cumulative cardiac injury through structural remodeling, including myocardial fibrosis, chamber dilation, and impaired contractility, while also disrupting electrical conduction pathways that regulate heart rhythm.

“Cardiac manifestations affect most DM1 patients,” said corresponding author Thomas A. Cooper, MD. “Cardiac problems are primarily electric conduction abnormalities, seen in up to 75% of adult DM1 cases, which can result in life-threatening arrhythmias accounting for 25% mortality and the second leading cause of death in DM1.”

DM1 is an autosomal dominant disorder and the most common cause of adult-onset muscular dystrophy. It is caused by an expanded CTG repeat in the DMPK gene, with affected individuals carrying between 50 and more than 4,000 repeats, compared to five to 37 in unaffected individuals. The expanded CTG repeat causes mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. The result is a loss of function of MBNL.

DM1 affects multiple systems, including skeletal muscle, the central nervous system, the gastrointestinal tract, and the heart. Cardiac impairment is common in people with the disease and is often fatal. Electrical conduction abnormalities, including prolonged PR, QRS and QTc intervals, atrioventricular block and bundle branch block, occur in up to 75% of adults with DM1. Patients may also develop atrial fibrillation, tachycardia and, less commonly, ventricular arrhythmias. Structural changes such as left ventricular dysfunction, hypertrophy, dilation and fibrosis contribute to morbidity and mortality. These conditions typically worsen with age and are more severe in males.

The Baylor team used a transgenic mouse model engineered to express toxic CUG repeat RNA in the heart. Unlike human disease, the number of CTG repeats in this model remained stable over time, allowing researchers to isolate the effects of prolonged RNA toxicity without the confounding factor of repeat expansion. The researchers measured the cardiac function of the mice over a period of 14 months.

According to the researchers, the data showed that “sustained CUGexp RNA expression caused progressive cardiac enlargement, contractile dysfunction, conduction delay, myocardial fibrosis, and reduced survival, while MBNL-dependent splicing defects remained static, consistent with the stable repeat length.” These findings indicate that cardiac deterioration can occur even without increasing loss of MBNL function. This finding runs contrary to current thinking, which centers on the role of repeat expansion as the primary driver of disease progression.

In this research, the model mice developed enlarged hearts and electrical abnormalities early on. Over time, these changes progressed to cause weakened cardiac function, fibrosis and dilation of heart chambers.

The study also sought to find whether the cardiac damage could be reversed by halting expression of the toxic RNA. When RNA expression was stopped after a short duration, heart size, electrical function and structure largely returned to normal.

Yet when exposure to the toxic RNA was prolonged, the mice did not exhibit complete recovery. While the molecular defects such as abnormal RNA splicing were fully corrected, structural damage, including fibrosis and conduction abnormalities, persisted. This shows that early intervention could be one method to prevent irreversible changes such as fibrosis, which disrupts electrical signaling and increases the risk of arrhythmias.

Prior research had linked increasing CTG repeat length with DM1 severity and earlier onset, but the extent to which other mechanisms contribute to progression remained unclear. By isolating RNA toxicity, the Baylor researchers have provided evidence that chronic cellular stress, structural remodeling and potentially other RNA-mediated effects play roles in disease pathology independent of repeat expansion.

Future research will look to identify any additional mechanisms that may contribute to disease progression, and will include studying the long-term effects of RNA toxicity, changes in RNA-binding proteins, and potential links to premature cellular aging.

The post RNA Toxicity Is a Driver of Heart Disease in Muscular Dystrophy appeared first on Inside Precision Medicine.

April 6, 2026

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