Cyclana Bio Is Exploring the Extracellular Matrix to Treat Endometriosis

Despite an estimated 190 million women and girls around the world living with endometriosis, a chronic and painful gynecological condition, no disease-modifying therapy has yet been approved to treat it. Léa Wenger, PhD, and her colleagues at Cyclana Bio are aiming to fix this.

Endometriosis occurs when endometrial tissue grows outside the uterus, causing inflammation, pain, and sometimes scarring and fertility problems. Although this condition was historically neglected in terms of research and development, Cyclana is now one of a small but growing group of companies trying to develop more effective endometriosis treatments. After completing a veterinary degree, Wenger shifted away from clinical practice when she discovered a passion for biomedical research during her PhD at the University of Cambridge. During this time, Wenger was diagnosed with endometriosis, which led her to co-found Cyclana Bio in 2024 with Kevin Chalut, PhD, who was her colleague at Altos Labs at the time.

The company joined the Babraham accelerator program last year and has already raised an oversubscribed £5 million ($6.8 million) pre-seed round. Wenger spoke to Inside Precision Medicine’s senior editor, Helen Albert, about her inspirations, career, and what she and her colleagues are hoping to achieve at Cyclana.

 

Q: What inspired you to become a scientist?

Léa Wenger, PhD
Léa Wenger, PhD

Léa Wenger: I was always very curious as a child. What drove me directly to science, rather than going for any other subjects, was my desire to be a vet. I wanted to be a vet and knew vets needed to know about science, so I decided to learn all the science I could. The irony of that was that I didn’t end up practicing a single day of veterinary medicine, but it got me into the doors of institutions where they teach you veterinary medicine in a way that was very scientific and research-driven. I really discovered a passion for science at that point, a passion for actually understanding things that we don’t know. I was exposed to this idea of driving knowledge where it isn’t present, and that was really what got me excited about research. That’s when I effectively shifted from the veterinary medicine career to the more traditional biomedical research route.

 

Q: What made you decide to go into biotech rather than staying in academia?

Wenger: I think the frustration I had in academia was that the system was set up to do a one-person, one-project type of research. That can be fun in some ways, but for me, it didn’t really address impact in the way that I really wanted it to. I wanted to feel like I was working towards creating discovery, translating it, and being able to improve patient lives. I just felt that biotech was a better conduit for that because it was based on faster-moving collaborative teamwork.

I was working in neurodegeneration at the time and on organoid models made of 3D stem cell-derived complex architectures. Organoid models are incredibly good at reproducing human development. But when you’re looking at neurodegenerative diseases that happen with age, it’s a lot harder. Aging in a dish is really hard to reproduce.

Cyclana Bio scientists
Cyclana Bio scientists working in the LiveLabs laboratory, from left to right, Kevin Chalut, PhD, cso and co-founder, Léa Wenger, PhD, ceo and co-founder,
Siiri Salooma, PhD, founding scientist, and Tom Wyatt, PhD, founding scientist.

It was at exactly then that I wanted to go down this research route in more detail that Altos Labs opened in Cambridge. The company had a thesis of “Let’s try and do real discovery science, deep, groundbreaking science,” but in a biotech environment where you’re much more collaborative. That really attracted me at the time, and so I applied to work there after my PhD. Luckily enough, they took a chance on me and believed in me.

I loved it and I learned a huge amount. Not just in terms of how you build discovery programs from the ground up, but also how you work in a team, how you focus, and how you align incentives in biotech. I think it completely shifted my mindset away from simple academic curiosity to, “How do we drive that curiosity towards impact as quickly as possible?” The bar, in my opinion, is somewhat higher than in academia because you’re not just saying, “Is this good enough to publish?” You’re saying, “Is this a therapy? Is this actually good enough to put into a human and help them and not harm them?”

 

Q: What made you decide to found Cyclana Bio?

Wenger: I was in an epigenetics lab within Altos, and my co-founder was actually one of the group leaders there working on the extracellular matrix. The more I worked with him, the more I realized how massively important it is in guiding how cells behave. You can get completely different responses from a cell depending on what environment it’s in. I got really interested in that interface between the epigenetics, the gene level regulation, and the [extracellular] matrix.

I was doing a lot of discovery science there, but during that time, I also developed endometriosis. I was in my mid-to-late 20s when my symptoms started, and they got worse very quickly. Like every scientist who gets diagnosed with a condition, I nerded out on the disease. In my spare time, I downloaded all the data and looked into what research was there, and very quickly realized that there wasn’t much information available.

There’s not much that we know about the disease and how it happens. People are still debating the causes and drivers of endometriosis. That was interesting and another area of unknown, which has always been what I was attracted to. I’d always been passionate about women’s health, but never really had the opportunity to do something about it.

There’s an easy, non-invasive way of getting access to cells to study endometriosis because menstrual fluid is built and shed every month from your endometrium. It’s built and shed in healthy women, in women with endometriosis, and in women with other conditions. On top of that, biopsies are actually way more common in gynecology than in a lot of other conditions. So I realized this was a huge opportunity to do this tissue-level discovery that we were so passionate about, but for a cause that I really believed in, in a field that was unknown.

I spoke to the CEO at Altos at the time and explained what I wanted to do. He was supportive and thought it was an interesting idea, but ultimately, the indication didn’t align with the priorities of Altos—of looking into age-related diseases. So that’s when we left and started Cyclana Bio.

 

Q: How easy was it to start the company?

Wenger: We were very lucky in that we got into the Babraham accelerator program very quickly, last May. That was important because not only did it give us validation that someone had actually picked us and said this is a good idea, but it also gave us lab space and access.

We did take quite a bit of a risk. Both my co-founder and I left without having raised funding or grants to start the company. For a short while, we were living off our savings and also paying for some very preliminary science and our first scientist to try and get some data going. That was in May [2025], but quite quickly, we got a bit of traction. By July, we had our first investment term sheet because we started fundraising immediately. Then by September, we were oversubscribed. We finalized the closing in October–November for a £5 million pre-seed round.

I think along the way, we basically just had to assume it was going to happen. We were building the company as if we had the money already, although we were always very open with Tom [Wyatt], the scientist who joined us first, about how much funding we had when he joined.

We’re nine people now and have some amazing scientists who have joined the team, including a great CTO who was also at Altos beforehand. We are still growing as we speak. It’s funny how science brings so much more science.

 

Q: What are you trying to achieve at Cyclana?

Wenger: Our main aim is to get at least one therapy that’s truly disease-reversing to the clinic. Based on a lot of research, we know that the extracellular matrix can guide how cells respond. It can act as a sink for particular signal factors. Sometimes it can sequester or deliver things like growth factors or inflammatory signals, but it also massively changes how the cell is interacting with its neighbors.

It’s a key component of a positive runaway effect that happens in lots of chronic inflammatory diseases and in some cancers. A lot of the time, when trying to develop treatments, we focus on the cells and whether we can stop that inflammation. What we think is, if you don’t address problems with the matrix, you are not going to cure the disease. You’re effectively just going to mitigate the side effects, and this matrix is going to act like a memory of the disease. This means that if you stop the treatment, it comes back because the matrix issue hasn’t been solved.

We think that that’s a big element of what’s going wrong with endometriosis. Lesions are removed surgically and then they come back. We really think the diseased extracellular matrix is very much driving the pro-inflammatory phenotype, and that if we don’t address that, we don’t actually get to the point where we are curing the disease. We want to see if we can effectively reverse the phenotypes and if we can effectively get to a cure by stopping this recurrent feedback loop.

We haven’t settled on an exact target or modality yet. We’re exploring a few different targets, and I think based on exactly what mechanism we want to go after, we will determine what the best modality is. We want to be sure about the science, very sure about the target, and then make that target work.

 

Q: Where does precision medicine come into your strategy?

Wenger: Our overall strategy is based on how we see endometriosis as a whole, but I think endometriosis hopefully won’t be viewed like that much longer. We hope that there’s going to be much better stratification and classification of the disease, because it manifests very differently in different women.

Although we think the extracellular matrix might be a common mechanism, we’re building a research platform where we will hopefully find out for sure because we’re collecting data. We’ve got an ongoing observational clinical study where we’re collecting biopsy tissue, menstrual fluids, clinical data, and blood from women, either with or without endometriosis.

We’re collecting that data, looking at the tissue, the proteins, and the architecture, but also isolating cells to test in our models. Then, when we start perturbing with particular interventions that we think might reverse the disease’s impact on the matrix or have different effects on the cells, we might start seeing patterns as to which types of women with endometriosis respond well to different treatments.

It’s going pretty well so far, thanks to our clinical collaborators and participants who have donated samples. Menstrual fluid is a very good way of getting samples from seemingly healthy women, because they don’t need to go to the doctor, [they] just send us a sample. We are also collecting tissue biopsies during routine gynecological procedures to minimize invasiveness and inconvenience.

So far, there’s lots of variability, which was what we expected and which is why we want to collect [samples from] a high number of donors. Not because we think that variability is noise, but because variability is signal. It can tell us more about the nuances of the disease in these different manifestations.

 

Q: What has the experience of being a CEO and biotech founder been like so far?

Wenger: It’s definitely been a steep learning curve. I think that’s also why it’s been so fulfilling, because I do love being in an environment where I’m not complacent, where I’m always learning.

To some extent, because we had so much freedom at Altos to drive our own projects, I had exposure already to the pure project management side of science, so that didn’t seem quite as much of a step up.

Obviously, there’s a huge business, commercial, and legal dimension that I never had thought about before. But I have been trying to learn as much as I can, as quickly as I can, from others. One thing that the biotech field is quite good at is volunteering information. You go to any sort of networking event, or you meet someone from the industry, and they are often very willing to talk to you about what they’re interested in, but also about what you’re doing, and give any advice they might have.

I’ve met many people who have helped me along the way and who have shared their opinions with me. I walked in expecting academia to be way more collaborative than the biotech industry, but actually, I’ve been very pleasantly surprised with my experience.

 

Q: Can you share any key learning experiences from the last year?

Wenger: If you have scientific training or you can think in a scientific way, going into the field of business or building a company is somewhat similar. There’s lots of information and lots of alternative paths that you can take, just like in scientific discovery, and there is differently weighted evidence as to which paths are the best ones to take. Once you have a certain amount of information, you can then take the best educated guess. That’s how I’ve gone about building the company. For example, when I started, I was told by a friend, “If you’re starting a biotech, you’re going to need to raise venture capital.” They gave me a book called Venture Deals, which is a very good book that explains how funds work. I read that book and felt I was better equipped to talk to people at the fundraisers. I think the first thing I’d say is, when going into any sort of field, try to really understand how and why that field exists and what are the structures that define its environment. Then you can put context into how people work. As a first-time founder, you might think, “I’m going to find investors, and if they believe in me, they’ll invest.” But there’s so much more to running a venture capital fund. Those things are important to know when framing your discussion.

Something I would do differently is not do everything at once. I left my job, started the company, started the science, started building the network, and started fundraising at the same time. There was always this pressure when I was meeting people that I also had to get them to invest. I think looking back on it, if I could start over, I probably would have spent a few more months trying to build my network and understanding the field better before I started having those investment conversations. It still worked out for us, we still raised funds, but it was stressful. Networking events were very high stakes!

 

Q: How has the endometriosis space changed in recent years?

Wenger: Gedeon Richter purchasing the Celmatix portfolio and backing FimmCyte are very good signs that people are trying again. I think endometriosis has been plagued by failures in clinical trials, and I think now we’re finally seeing some non-hormonal options being tested, which makes me hopeful. Some will fail, some will succeed, and the successes will drive more interest and availability of funding and hopefully, more successes in the future. I’m really looking forward to seeing the results from some of those clinical trials because I think the more solutions we have for women, the better.

 

Q: Is funding in the overall field of women’s health changing for the better?

Wenger: Absolutely. I think the funding environment is more open to women’s health. I think that’s been helped by the World Economic Forum and McKinsey Health Institute driving the message of value there. There is excitement, I think, and more funding, especially privately.

I’m not sure about public funding. I do think that on the public funding side, we have a trend of saying, “We should fund women’s health, let’s look for quick wins.” I think that’s a bit of a problem with any field that’s been somewhat left behind, once we realize that we need to bring it back. The risk will be funding the wrong things or putting too much of the money into solutions that may not be revolutionary because they don’t have the foundational science to back them up.

It can also be easy to get stuck in the valley of death between seed and late-stage funding. But I do think that there are incredible scientists moving into the field, and there are some great companies starting up. So even if there is this bias towards pre-seed or seed funding, you only need a couple of those companies to have some really promising data, and they will be funded. The bar might be higher than in other fields, but if you produce groundbreaking discoveries, there will be money.

 

Q: What advice would you give other new founders starting to build their companies?

Wenger: Just follow your gut and your dream. That’s the most important thing. I started Cyclana because I thought this needed to happen and we needed to look into endometriosis. I thought it was a bit hypocritical of me to think we needed to do something and not do it, despite having the training and the skills to try and find a solution. If you really believe something needs to happen in the world, startups are the best way to feel like you are driving that change and contributing to seeing the change that you want to happen. Whether it succeeds or not, you won’t wake up thinking, “What am I doing this for?” You’ll just be thinking, “I really hope that we don’t fail!”

 

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.

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<![CDATA[Let’s take a look at the next generation of pharmacotherapies for mood and anxiety disorders. ]]>

Nonprofit buys experimental cancer drug to maintain patient access

In a rare move, nonprofit organization Blood Cancer United announced Thursday it was buying the remaining supplies of Luvelta, a discontinued investigational cancer drug.

As part of the transaction, Blood Cancer United, previously known as the Leukemia & Lymphoma Society, also will acquire the investigational new drug designation and manage the compassionate-use program for children with a rare form of blood cancer, distributing the medication to patients at no cost while supplies last.

Read the rest…

Higher Vitamin C Levels in Blood Linked to Healthier Aging Brains

Researchers in Japan have found that older adults with higher levels of vitamin C in their blood have a higher volume of gray matter in their brains and higher connectivity across brain regions involved in memory and attention. Published in PLOS One, their study raises the possibility of using dietary interventions to protect brain health as we age. 

“What I found most fascinating about this research is that we were able to detect these subtle but significant associations between a single nutritional factor and large-scale brain networks by utilizing a robust, community-based cohort of over 2,000 older adults,” said Tomohiro Shintaku, MD, PhD, assistant professor of radiology at the Hirosaki University Graduate School of Medicine. “It truly highlights the potential impact of our everyday dietary habits on our brain structures.”

Previous research had linked diets high in vitamin C with lower risk of developing cognitive impairment in older adults. However, this study is the first to look directly at a potential link between vitamin C levels in blood and changes in brain structure and connectivity within a large participant cohort. 

Shintaku and colleagues analyzed magnetic resonance imaging (MRI) scans and blood levels of vitamin C in 2,044 Japanese adults over the age of 64. They measured the volume of gray and white brain matter in each individual, as well as the connectivity between brain regions belonging to the default mode network, which are associated with important cognitive functions including autobiographical memory, future thinking, self-reference, and attention. Connectivity within the default mode network is also known to play a significant role in brain health, with lower connectivity being linked to cognitive impairment and Alzheimer’s disease, in addition to a number of psychiatric conditions including depression or schizophrenia. 

After adjusting for other factors that affect brain structure and connectivity, such as age, physical activity, and education level, results showed that higher levels of vitamin C were associated with a higher volume of gray matter across several brain regions, and with higher connectivity within the default mode network. 

“Our study demonstrates that higher plasma vitamin C levels are associated with better preserved structural connectivity of the default mode network, a key brain network involved in cognitive function,” said Shintaku. “This finding generates the exciting hypothesis that a diet rich in vitamin C might play a supportive role in maintaining brain health and mitigating age-related cognitive decline in older adults.”

More research will be needed to uncover the potential biological mechanisms driving this association and confirm whether there is a causal link between blood levels of vitamin C and changes in brain structure and connectivity. Going forward, the researchers plan to conduct studies looking at repeated measurements of vitamin C levels over time, accounting for additional lifestyle and nutritional factors that may influence these effects, and including cohorts with more diverse ethnicities and socioeconomic status. 

The post Higher Vitamin C Levels in Blood Linked to Healthier Aging Brains appeared first on Inside Precision Medicine.

Stopping Neurodegeneration in Place with Vaccines

Developing truly disease-changing treatments for Alzheimer’s disease and other neurodegenerative conditions has proved challenging, with many failed trials over the last few decades. The approval of Eisai/Biogen’s monoclonal antibody lecanemab in 2023, the first such treatment to have a positive, albeit modest, impact on symptoms of Alzheimer’s disease, was therefore received with enthusiasm by many.

Critics of lecanemab and Eli Lilly’s donanemab, approved a year later for the same indication, argue that the small benefit gained from the drugs does not outweigh the economic costs, possible side effects, and burden of regular intravenous infusions.

Using a vaccine-style approach, where the treatment prompts the body to generate its own antibodies, has the potential to solve these problems. Several companies are developing active immunotherapies to target Alzheimer’s and Parkinson’s disease, as well as other neurological conditions.

Andrea Pfiefer
Andrea Pfiefer, PhD
CEO and Co-founder
AC Immune

“What we’re trying to do is link the antigen to a carrier and bring it into a form which mimics the pathology,” explained Andrea Pfeifer, PhD, CEO and co-founder of Swiss company AC Immune, a leading biotech taking the active immunotherapy route to target Alzheimer’s and Parkinson’s disease.

“We inject it into the immune system, and what it recognizes is the misfolded protein. So, because of that, the immune system only makes antibodies against this pathological protein.”

Although none have yet reached the market, the active vaccine-style approach potentially has a number of advantages over passive treatment with monoclonal antibodies. Importantly, fewer rounds of treatment are required. The exact dosing is yet to be determined, but it would certainly be less frequent than the regular infusions of lecanemab or donanemab that are currently prescribed. This would help reduce costs and treatment burdens for patients and their families. There is also likely to be less risk of amyloid-related imaging abnormalities (ARIA) due to the relatively slower onset of antibody generation by the body.

“If you have to take the patient every two to four weeks to get a two-hour infusion in a hospital, and then you have to wait and do imaging, it’s really burdensome,” said Pfeifer.

“After a certain while, they just don’t want to go. … They say, ‘Sorry, we believe your science, we believe everything, but we don’t want this.”

To date, most vaccine trials have enrolled people with at least some degree of Alzheimer’s or Parkinson’s disease, as preventive vaccine trials need to be large and long in duration. Theoretically, developing a preventive vaccine is a feasible approach, as many neurodegenerative diseases typically have a slow onset before noticeable symptoms appear. However, reliable biomarkers that can accurately predict disease onset have been in short supply.

Alzinova’s ALZ-101
ALZ-101 – Alzinova’s disease-modifying vaccine candidate for Alzheimer’s disease

This is changing, though. Last year, two blood tests that measure phosphorylated tau and amyloid ratios were approved by the U.S. Food and Drug Administration (FDA) for Alzheimer’s diagnosis. The biomarker field is less developed for Parkinson’s and other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), but things are slowly improving.

Promising mid-stage results from front-runners like AC Immune and Alzinova suggest that this pathway has merit, but whether they can succeed in larger registrational trials going forward is unclear.

Tord Labuda
Tord Labuda, PhD
CEO, Alzinova

“It remains to be seen how our immune system reacts. I think that when we look at the titers we see from the vaccine, they’re similar to what we get with passive immunizations. So I think there are a lot of things that point in the right direction,” said Tord Labuda, PhD, CEO of Swedish biotech Alzinova, which has an amyloid beta vaccine in development.

“Personally, I don’t think that the vaccine or passive immunization is the real challenge. The real challenge is to have the right target.”

Taking a more active approach to immunotherapy

While passive immunotherapies like lecanemab and donanemab are groundbreaking in that they are the first disease-modifying treatments for Alzheimer’s to be approved by the FDA and they slow cognitive decline by around 25%–35% over two years, these drugs can cause significant side effects such as ARIA.

This can cause brain swelling and bleeding in some people. Individuals at highest risk for some neurodegenerative conditions, such as carriers of the APOE4 gene variant, are prevented from accessing these therapies at all, as they have a higher-than-average risk of experiencing ARIA-like side effects.

Treating neurodegenerative diseases like Alzheimer’s and Parkinson’s disease when symptoms commence is problematic, as currently, there is no known method of regaining neuronal function once it has been lost.

Classic pathology studies suggest that, by the time the typical motor symptoms of Parkinson’s appear, around 50%–70% of dopaminergic neurons are already lost from the brain. Similarly, in early clinical Alzheimer’s disease, where those affected have mild dementia, hippocampal volume in the brain seen on imaging is already up to 25% lower than that of age-matched controls. This means, however good the treatment is, the patients will never regain complete function.

“There’s no way we can restore these neurons,” said Roman Kniazev, CEO of U.S.-biotech Nuravax, which is developing several different Alzheimer’s vaccines. “They are gone forever. So that is why the best strategy, and this is our motto in our company, is to not let the pathology kill the neurons.”

Researchers trying to develop new therapies for Alzheimer’s and Parkinson’s are increasingly moving towards an early or even preventive approach. The idea of a vaccine-like approach to targeting Alzheimer’s is not new. Animal work in the late 1990s showed that vaccinating against amyloid‑beta could clear plaques and improve cognition in transgenic mouse models. This led to the development of Elan/Wyeth’s amyloid‑beta vaccine, AN1792.

It entered Phase I/II trials for mild‑to‑moderate Alzheimer’s and successfully induced anti‑amyloid beta antibodies in some patients. But the study had to be stopped in 2002 because around six percent of the participants developed meningoencephalitis, linked to T cell–mediated inflammation in the brain. Despite strong amyloid plaque clearance, there was little impact on symptoms in the clinical trial participants.

Several other candidates, designed to avoid the T-cell activation seen with AN1792, have been unsuccessfully trialed over the last two decades. Although largely safe and antibody-producing, most of these programs were discontinued due to a lack of efficacy.

The field has persevered despite this, with improvements in technology, safety, biomarkers, and clinical trial design having led to a new generation of vaccine candidates that, while not yet approved, are showing good results in Phase I and II trials.

Neil Warma
Neil Warma
CEO, ProMIS Neurosciences

“I think what we’ve learned over the past five or 10 years from other vaccine approaches is that the next generation are those that come with a very precise approach to generating antibodies against the toxic species of a given protein for that specific neurodegenerative disease,” said Neil Warma, CEO of ProMIS Neurosciences, a U.S.-based company taking an antibody and a vaccine-based approach to treating Alzheimer’s and other neurodegenerative diseases.

“Those are really the things that make the vaccine approach much more interesting now. The sophistication of the biomarkers, the data we’ve learned from past and current products in the market, and then this ability to design and create antibodies that are highly specific to a targeted pathogenic form of the protein.”

AC Immune has three active immunotherapy candidates in Phase II: an anti-amyloid beta therapy, ACI-24, that is being developed with Takeda; an anti-tau therapy, ACF 35, being developed with Johnson & Johnson; and an anti-alpha synuclein candidate targeting Parkinson’s disease.

Staining of neurons in the brain
Staining of neurons in the brain from Neil Cashman’s lab-1.

The company reported good results for its Parkinson’s Phase II study at the end of last year. The interim study results showed a 100% response rate and a good safety profile in people with early Parkinson’s disease. Alpha-synuclein and neurofilament light levels in the blood, as well as scores from standard movement tests, suggested that disease stabilization had occurred.

If confirmed by results from the second part of the study, this would be the first time that disease modification, rather than symptom management, has shown promise for Parkinson’s disease. It would also confirm alpha synuclein as a pathogenic contributor to the condition.

“The statistical variability was very, very small, which was a surprise to us. Every single marker, preclinical biomarker, clinical imaging, went into the same direction,” said Pfeifer. “For me, what was particularly rewarding was that there was a connection between the titers, so the antibody response in the people versus the reduction of this pathology … the alpha-synuclein versus the imaging, which showed that the neurons can be protected.”

Better targeting to improve safety and efficacy

A common theme among vaccine developers in the neurodegeneration space is precision targeting. There is a strong consensus that a lack of specificity when picking targets is likely why many trials failed to show efficacy and had significant side effect issues in the past.

Different companies or research groups back slightly different protein targets, but the experts all emphasize the importance of avoiding binding to inert plaque in the brain in Alzheimer’s disease, and of targeting toxic, misfolded proteins that are disease-specific.

“We provide the body with active immunotherapy, and then the body induces the antibodies. But what is important is that these antibodies are really specific for the pathological form,” said Pfeifer.

AC Immune is not the only company with a keen focus on tightening up targeting in this area. Alzinova is specifically targeting toxic amyloid beta oligomers with its lead candidate ALZ-101, a therapeutic Alzheimer’s vaccine.

It received a recent FDA Fast Track designation for ALZ-101 after good safety and efficacy data were reported last year from its completed Phase Ib clinical trial.

“They have shown in many in vitro and in vivo models that … when you remove these toxic oligomers using antibodies towards them, you can basically neutralize the toxicity in these extracts towards the neurons,” explained Labuda.

He added that many of the “vaccines, as well as the monoclonal antibodies, are going for the N-terminal part of the protein. … By doing that, you will target the monomers, all the fibrils, but most importantly, also the plaques. Very little will be left to bind to something else that might be more important for the disease. I think this is what we see with the current treatments on the market. There’s a lot of off-target effects … and that’s why we have these huge challenges.”

ProMIS is also targeting amyloid beta oligomers in Alzheimer’s using both a monoclonal antibody and vaccine approach. It has developed a special method with the help of artificial intelligence to develop antibodies, taking both conformational shape and protein sequence into account.

“These three-dimensional shapes don’t exist on monomers, and they’re buried in plaque. We’ve tried and tried and tried to get these antibodies to bind monomers, to bind plaque, and they really don’t, which is good,” said Warma.

“We’ve done side-by-side testing with other antibodies to see if ours is truly differentiated. … In many different studies before we got to the clinic, PMN-310, our therapeutic antibody, was the only one that bound oligomers and avoided monomers and plaque. All the others cross-reacted with everything.”

ProMIS is testing its PMN-310 antibody before moving on to the vaccine approach. “If we can come with that one-two punch to say we’ve got a drug now that can treat patients with Alzheimer’s, we’ve got the ability to detect the onset of disease pathology in Alzheimer’s, and we have a vaccine that prevents you from developing that disease, I mean, that would be a pretty powerful combination,” noted Warma.

Nuravax is aiming to address two key shortcomings of first‑generation Alzheimer’s vaccines, such as AN1792: the risk of problematic T cell-driven inflammation and uneven immune responses in older adults. Its MultiTEP‑based candidates (AV‑1959R, AV‑1980R, and Duvax) are engineered to elicit a strong, antibody‑dominant response against amyloid‑beta and tau while minimizing activation of potentially autoreactive T cells and maintaining effectiveness.

“The platform which we developed makes the vaccine highly immunogenic, and this high immunogenic feature is essential for diseases in the brain,” said Kniazev.

Kiran Bhaskar
Kiran Bhaskar, PhD
Professor
University of New Mexico

Kiran Bhaskar, PhD, is a professor and group leader at the University of New Mexico. He has worked on Alzheimer’s disease for many years and is also a scientific co-founder of TheraVac Biologics. He and his colleagues are developing an anti-tau Alzheimer’s vaccine that is about to start human trials.

They are also aiming to reduce risks associated with immune reactions to vaccine adjuvants, which can contribute to ARIA, and have created a vaccine that does not need an adjuvant.

“We use a strategy called a virus-like particle,” he explained. “You don’t need to expect any side effects because of adjuvants. In this way, we trick the immune system into thinking that there is a viral attack on the body. It immediately starts an immune response against the virus-like particle and also anything sticking to the surface of those virus-like particles, which in this case is pathological or phosphorylated tau proteins.”

Overall, in the trials carried out so far in the active immune therapy space in Alzheimer’s disease, rates of ARIA have been very low, which is another selling point for the vaccine approach. “We don’t expect to see ARIA in active immunotherapy because we are using the host’s own immune response system to generate antibodies. … So that way there’ll be less unanticipated immune response,” explained Bhaskar.

syringe and vaccine bottle
Credit: Ake Ngiamsanguan / iStock / Getty Images Plus

Overcoming challenges on the road to the clinic

There is no doubt that active immunotherapies or vaccines to target Alzheimer’s and Parkinson’s disease are more advanced than they have ever been before, but they are still a long way from a mainstream rollout.

One reason the conversation has shifted is that the approval and broader use of the first anti-amyloid antibodies, for all their modest effect sizes and ARIA issues, shows that lowering the right protein species can slow deterioration. Using a more vaccine-like approach, where people make their own antibodies, does have the potential to make targeting these conditions safer, cheaper, and more accessible for patients.

But basic clinical questions remain unanswered. For example, how long vaccine-induced protection will last, how often boosters will be needed, and whether early stabilization of biomarkers and motor or cognitive scores—such as AC Immune’s interim Parkinson’s data or Alzinova’s Phase Ib Alzheimer’s study results—will translate into true preserved function a decade later.

Biomarkers are a big potential stumbling block for the development of preventive vaccines. The position is better for Alzheimer’s disease; the FDA’s approval of two blood-based Alzheimer’s biomarkers now gives developers a way to find people with silent pathologies without relying solely on positron emission tomography imaging. But there is still a lot more to do on this front, particularly in diseases like Parkinson’s, ALS, or other neurological or neurodegenerative diseases where less is known.

surgical glove pointing at a brain scan image
Credit: Martin Philip / iStock / Getty Images Plus

“We need better and safer treatments, but it’s also linked to having the right biomarkers, because if you have a risk factor, it doesn’t mean necessarily that you have the disease,” said Pfeifer. “These biomarkers are still not very well established. … The goal is absolutely to go to preclinical, and preclinical will require these biomarkers. If you ask me what is needed most in Parkinson’s right now, [it] is definitely to have better biomarkers.”

A second stumbling block for companies that want to develop vaccines that can effectively immunize people against neurodegenerative disease is that clinical trials of vaccines in populations of people with no symptoms have historically been large, expensive, and time-consuming—something out of reach of most biotechs without significant outside investment.

ProMIS and others are hoping that the efficacy of their therapeutic antibodies will boost their vaccine pipeline in the future. “If we show that it works in Alzheimer’s, then a similar approach should work in these other diseases,” said Warma. “Since it’s an almost identical process for vaccines, it also shows proof of concept for this whole wave of vaccines coming behind it.”

For now, active immunotherapies promise something that is more modest than true disease prevention but still crucially important. Namely, cheaper, less burdensome, and potentially safer ways to target the same disease biology as today’s monoclonal antibodies, ideally years earlier in the process.

The post Stopping Neurodegeneration in Place with Vaccines appeared first on Inside Precision Medicine.

Remote Monitoring Benefits Unclear After Hospitalization for Serious Infection

Remotely monitoring patients after they have been released from the hospital for serious infections does not reduce their risk of readmission, particularly for older adults, a randomized trial suggests.

The findings, released simultaneously in JAMA Network Open and at the Critical Care Reviews annual meeting in Belfast, emphasize the importance of studying potentially beneficial care models in real-world scenarios.

Remote monitoring involves the use of resources such as smartphone-based questionnaires, internet-connected scales, or blood pressure monitoring to allow patients to leave hospital.

These enable clinicians to monitor health from afar, while acting on alerts to ensure timely care.

While patients might prefer this type of care, the trial suggested that remote monitoring should be re-evaluated and individually tailored after acute care for sepsis and lower respiratory tract infections.

It did not increase the days patients spent at home and did not support U.S. federal agency efforts to reduce hospital readmissions by reimbursing remote monitoring.

“Health systems, insurers and policymakers all want to reduce hospital readmissions, and most patients prefer to recover safely at home,” explained lead researcher Sachin Yende, PhD, from the University of Pittsburgh.

“Remote monitoring has been held up as a solution, is reimbursed by the Centers of Medicare & Medicaid and its use has grown. But, aside from a few conditions, there’s a dearth of high-quality data to show it reduces readmissions.”

In an attempt to source this information, Yende and team conducted a complex trial in 1286 adults, with a median age of 63 years, who were recovering at home after hospitalization for sepsis or lower respiratory tract infections at 19 institutions. Of these patients, 32.6% received intensive care.

Participants were randomly assigned to one of four remote monitoring strategies or usual care.

Usual care generally involved a phone call from a nurse after discharge followed by continuing management from a primary care physician. The remote monitoring interventions consisted of short or long health questionnaire with standard or enhanced clinical response teams.

The standard response involved nurses who responded to alerts highlighted in the questionnaires together with coordinated care involving the patient’s primary and specialty clinicians.

Enhanced care included certified registered nurse practitioners with palliative care expertise who could coordinate some of the care response and also access social workers.

The primary endpoint was days at home at 90 days after discharge.

The trial showed that remote monitoring programs with high- or low-intensity questionnaires combined with a nurse response team or a nurse practitioner-led response team did not increase the time spent at home.

At least one readmission occurred among 37.8% of patients in the control group, receiving usual care.

This compared with 39.7% in patients receiving the shorter questionnaire and standard response team, 44.2% for those receiving the long questionnaire with standard clinical response, 37.3% receiving the shorter questionnaire but enhanced response team, and 36.3% for those receiving the long questionnaire with enhanced clinical response.

These differences did not reach statistical significance.

However, among patients aged 65 years and older, the remote monitoring programs did reduced time spent at home and increased readmission rates compared with usual care.

In this older age group, both the standard and enhanced response groups had fewer home days compared with usual care, with corresponding cumulative odds ratios of 0.56 and 0.67.

“These findings support reevaluating and tailoring remote monitoring in post–acute care following sepsis and lower respiratory tract infection to support further alignment with patients’ needs and desire for personalized monitoring,” the researchers concluded.

The post Remote Monitoring Benefits Unclear After Hospitalization for Serious Infection appeared first on Inside Precision Medicine.

Potential Cocaine Addiction Targets Identified Through Genetic Mapping in Rats

Scientists at the University of California San Diego have reported the results of a genome-wide association study in rats that identified key biological drivers of cocaine addiction. Using a genetically diverse group of nearly 900 rats to map genetic markers associated with compulsive drug use, the researchers uncovered a potential new therapeutic target that resides in the liver rather than in the brain.

Current research in this field often focuses on the brain, but the UC San Diego team’s findings suggest that how the body metabolizes cocaine may be just as critical in determining whether somebody develops an addiction.

“Finding a liver-based enzyme that shapes cocaine-taking behavior was a real ‘aha’ moment for us,” said Olivier George, PhD, a professor of psychiatry at UC San Diego School of Medicine. The George lab led the addiction behavioral studies that provided the foundation for the research. “It reminds us that addiction isn’t only in the brain. It’s a complex puzzle involving how the entire body processes the drug.”

George is co-corresponding author of the team’s published paper in Nature Communications, titled “Genome-wide association study of cocaine self-administration behavior in Heterogeneous Stock rats.”

Cocaine use disorder (CUD) has a strong genetic component, the authors noted. “Twin studies estimate the heritability of cocaine dependence to be as high as 70%, a finding supported by recent comprehensive reviews,” they wrote.  GWAS have also uncovered a significant heritable component, the team continued, with single nucleotide polymorphism (SN)-based heritability estimated at 27-30%. However, scientists have struggled to pinpoint the specific genes that make certain individuals more vulnerable to addiction.

“The paucity of significant and replicated associations for CUD limits our understanding of this disorder, hampering our ability to identify novel pharmacological targets,” the investigators added. Co-corresponding author Abraham A. Palmer, PhD, professor of psychiatry at UC San Diego School of Medicine, who led the project’s intensive genetic modeling and analysis, further commented, “Identifying those genes in an important goal, because drugs could then be developed to target those genes, shifting genetically susceptible people to become more like genetically resistant people.”

To investigate further, the team carried out a GWAS in nearly 900 outbred Heterogeneous Stock (HS) rats—a model system capable of mimicking the vast genetic diversity found in human populations. By using HS rats the team was able to capture the critical differences between individuals who are genetically susceptible to addiction and those who are naturally more resistant. “Prior work has established the phenotypic diversity of HS rats across a broad range of addiction-relevant behaviors, including cocaine self-administration,” the researchers commented.

“The extended access model allowed us to characterize escalating intake, increased motivation to take the drug, and compulsive-like behavior despite negative consequences.” In addition to the GWAS results the researchers carried out a range of secondary analysis strategies to uncover what they describe as novel genetic drivers of cocaine self-administration behaviors.

Analyzing millions of genetic markers in each animal, the team discovered six major genetic regions linked to addiction-like behaviors, such as the escalation of drug intake and the time elapsed between doses. The researchers identified in the rats a specific group of carboxylesterase genes that are orthologous to the human CES1 gene, which are responsible for creating the enzyme that metabolizes cocaine. The study found that variations in these genes are closely linked to how frequently and compulsively rats self-administered the drug.

The findings also replicated a known genetic link found in humans (Trak2), providing a vital translational bridge between animal research and human medicine. This replication strengthens the argument that the biological pathways identified in the lab could eventually lead to real-world therapies. “Genes associated with CUD in humans remain limited, however our GWAS identified one gene (Trak2) that has also been identified by human GWAS of CUD, and the novel identification of Ces1 offers a fresh avenue for future studies,” they stated.

The collective findings suggest that by targeting the enzymes that metabolize cocaine with medicines, scientists might be able to alter how the drug affects the body, potentially reducing its addictive impact. In their paper they concluded “Our results replicate previous loci associated with CUD in humans and provide several novel biological insights including the potential of pharmacological strategies targeting carboxylesterases.”

Palmer said, “This work showcases the power of long-term, team-science collaboration that pairs experts in rodent behavior with quantitative geneticists. A decade of coordinated effort across multiple cohorts and federal partners made possible a discovery that no single lab could achieve alone.”

First author Montana Kay Lara, PhD, a postdoctoral researcher at UC San Diego School of Medicine, who helped bridge the gap between the study’s behavioral and genetic components, said, “Seeing the Ces1 signal validate a hypothesis that has been circulating for decades is incredibly exciting. It gives us a concrete target to test whether changing how cocaine is metabolized can blunt the drive toward compulsive use.”

The research team is now moving into the next phase of the project, which involves investigating exactly how these genetic mutations change function of the enzyme. They also hope to use the study’s extensive Preclinical Addiction Biobanks—collections of blood, urine, brain and other tissue samples—to identify biological markers that could one day help predict an individual’s risk of developing a substance use disorder.

The researchers hope that by leveraging this resource, they and other scientists working in this space will be able to translate genetic discoveries into diagnostic tools and new treatments that can help stabilize individuals struggling with addiction.

The post Potential Cocaine Addiction Targets Identified Through Genetic Mapping in Rats appeared first on GEN – Genetic Engineering and Biotechnology News.

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App-Based Physical Activity Intervention for Individuals With Depression (MoodMover): Single-Arm, Pre-Post Proof-of-Concept and Feasibility Study

Background: Depression is a prevalent mental disorder, and it remains one of the leading causes of disability in Canada and globally. Mobile app–based physical activity interventions may offer an effective and accessible treatment option for individuals with depression who cannot or prefer not to access supervised exercise programs. Objective: This study aims to investigate the feasibility, acceptability, and proof of concept of a 9-week, theory-guided, app-based physical activity promotion intervention (MoodMover) developed for people with depression. Methods: We conducted a single-arm, pre-post study from November 2024 to May 2025, following the phase IIa: Proof-of-concept and phase IIb: Pilot and Preliminary Testing of the Obesity-Related Behavioural Intervention Trials model. Physically inactive adults who either self-reported a diagnosis of major depressive disorder or reported at least mild depressive symptoms, operationalized as a minimum score of 5 on the Patient Health Questionnaire, 9-Item, were recruited. The intervention spanned 9 weeks, with the first week serving as a run-in period and including a 15-minute orientation session on the first day. Participants were instructed to use the MoodMover program, delivered via the Pathverse app. Feasibility was assessed based on 4 primary criteria: recruitment, adherence, usability, and retention. Proof-of-concept was evaluated by assessing changes in physical activity behavior and depressive symptoms over the intervention period. Results: From November 2024 to March 2025, 32 of the 51 adults who met eligibility criteria consented to participate in this study, resulting in a recruitment rate of 63%. Twenty-eight participants completed baseline assessments, with a mean age of 39.8 (SD 13.4) years. A total of 21 participants attended the orientation session and received the intervention. Retention, adherence, and usability rates were 57% (16/28), 67% (14/21), and 50% (8/16), respectively. Regression analyses found that age consistently associated with app engagement, usability, and satisfaction. Two-tailed paired tests indicated significant pre-post changes in self-reported moderate to vigorous physical activity and depressive symptoms across the 75%, 85%, and 95% CIs. Among participants with clinically elevated depressive symptoms at baseline (Patient Health Questionnaire, 9-Item ≥10), 75% (9/12) achieved a clinically meaningful reduction in symptom severity. Conclusions: Our findings suggest that MoodMover holds potential for promoting physical activity behavior among individuals with depression and supporting depression management at scale. However, the feasibility of the tested version remains suboptimal. Necessary modifications (eg, improvements to enhance the accuracy of step tracking) should be implemented and reevaluated before progressing to a more rigorous efficacy trial. Trial Registration: ClinicalTrials.gov NCT06573125; https://clinicaltrials.gov/study/NCT06573125
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A Self-Guided Web-Based Transdiagnostic Mental Health Program for People With Intellectual Disability: Single-Arm Trial

Background: People with intellectual disability experience rates of mental illness up to 3 times higher than the general population, yet face significant barriers to care, including limited clinician expertise, diagnostic overshadowing, and exclusion from key mental health services. Electronic mental health interventions have demonstrated effectiveness in the general population and may address these barriers for people with intellectual disability by providing accessible, tailored treatment. Objective: This study examined the ability of Healthy Mind, a self-guided, web-based transdiagnostic mental health program designed specifically for people with borderline to mild intellectual disability, to reduce symptoms of anxiety and depression and improve functioning in people with intellectual disability. Methods: In a single-arm uncontrolled design, Australian residents aged ≥16 years with a diagnosis of borderline or mild intellectual disability, and mild-to-moderate symptoms of depression or anxiety on the Anxiety, Depression, and Mood Scale (ADAMS) were recruited online and offered access to Healthy Mind. Assistance from a nominated supporter was optional. Primary outcomes were symptoms of depression and anxiety (ADAMS). Secondary outcomes were psychological distress (Kessler Psychological Distress Scale [K10]) and functional impairment (World Health Organization Disability Assessment Schedule 2.0 [WHO-DAS]). Outcomes were assessed at baseline, 8 weeks, and 3 months. In total, 80 participants (mean age 27.8, SD 7 y; n=37, 46% female; n=39, 49% identifying as Aboriginal and/or Torres Strait Islander) enrolled; 61% (n=49) nominated a supporter. Data were analyzed using multilevel models with random intercepts for participants. Results: No significant changes were found in ADAMS depression or anxiety scores from baseline to postintervention or follow-up. Similarly, no significant effects were found for K10 or WHO-DAS scores, except for an improvement in K10 scores between baseline and 3 months when controlling for cognitive functioning (n=15). Having a supporter was associated with lower baseline distress but did not moderate treatment effects. Engagement with Healthy Mind was low; 42.5% (n=34) did not access the program, and among those who did, the median number of completed modules was 7 (IQR 3-11). Greater module completion was associated with slightly higher WHO-DAS scores post intervention. Conclusions: This trial did not demonstrate significant improvements in mental health or functioning associated with Healthy Mind, likely due to low engagement, reduced statistical power, and the absence of a control group. Nonetheless, the study demonstrates the feasibility of recruiting and retaining people with intellectual disability in fully online trials and highlights the urgent need for strategies to improve engagement, including gamification, personalized content, and integrated social features. Electronic mental health remains a promising avenue for addressing the substantial mental health service gap for people with intellectual disability. Trial Registration: ANZCTR ACTRN12620000113954; https://tinyurl.com/2ecdmde8 International Registered Report Identifier (IRRID): RR2-10.3390/ijerph18052473
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