Alzheimer’s drug demonstrates efficacy against sickle cell anemia

University of Zurich

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The blood of a sickle cell patient under a light microscope. The sickling of the otherwise round red blood cells is clearly visible. 

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Credit: University of Zurich

Sickle cell anemia is the world’s most common genetic disorder. It causes the red blood pigment hemoglobin to crystallize, which results in rigid, malformed red blood cells with a sickle shape. This impairs the cells’ mobility and causes severe complications, including circulatory disorders, organ failure, a significantly shortened life expectancy and reduced quality of life – especially in children and adolescents.

The disease, which is hereditary, can be treated with hydroxyurea. When taken regularly, this drug can improve quality of life; however, it is not well tolerated by all patients. A bone marrow transplant is another possibility, but there is a lack of suitable donors and other treatments, such as gene therapies or therapeutic antibodies, come with extremely high costs. Now, an international team led by Max Gassmann, professor emeritus of veterinary physiology at the University of Zurich, is pursuing an alternative and significantly more cost-effective approach. More specifically, they are investigating the potential application of the Alzheimer’s drug memantine in the treatment of sickle cell anemia, a use outside its approved indication. Memantine has been used to treat Alzheimer’s disease for about 20 years, meaning it is no longer patentable.

The potential of an inexpensive active ingredient

In previous preclinical studies, researchers demonstrated that memantine has a stabilizing effect on red blood cells. They then investigated the drug’s safety and tolerability in a phase II study. “In the best case, memantine would be available for the treatment of sickle cell anemia, as a well-tolerated, easy-to-store, and very cost-effective drug that is no longer patent-protected,” says Max Gassmann. This would be particularly significant for countries with a high disease burden and limited resources, for example Africa or certain places in India.

Fewer and shorter hospitalizations

A total of 17 study participants received age-appropriate doses of memantine for 12 months. The research team took several key findings from the study: the treatment was well tolerated, and more than 25 laboratory parameters confirmed the drug’s safety over a period of two to three years. At the same time, a clear clinical benefit was demonstrated: both the number and duration of hospitalizations decreased significantly. Children in particular experienced fewer painful flare-ups. No serious side effects or discontinuations of the study due to the therapy itself were observed.

Follow-up study planned

All patients involved in the study continued their existing hydroxyurea therapy, as discontinuing it would have been unethical. “The observed effects should therefore be interpreted as complementary to hydroxyurea,” Gassmann explains. The research team is now planning a follow-up study that will, for the first time, include patients who have not received hydroxyurea treatment, in order to allow a systematic analysis of combination therapies. This approach aims to evaluate the clinical efficacy of memantine in a comprehensive and evidence-based way.

References

Ariel Koren, Carina Levin, Leonid Livshits, Fabio Valeri, Sari Peretz, Sivan Raz, Anna Yu. Bogdanova, Max Gassmann. MeMAGEN: a phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients. HemaSphere. 11 January 2025. DOI: 10.1002/hem3.70278

Contact

Prof. emeritus Prof. h.c. Dr. Max Gassmann
Institute of Veterinary Physiology
University of Zurich
+41 44 635 88 03
E-mail: maxg@access.uzh.ch

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Journal

HemaSphere

DOI

10.1002/hem3.70278 

Method of Research

Randomized controlled/clinical trial

Subject of Research

People

Article Title

MeMAGEN: a phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients

Article Publication Date

11-Jan-2026

 

Early intervention of cyanobacterial risks starting from the genome?

Science China Press

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Once the foundation of life on Earth, they have now become “hidden bombs” in water bodies. Cyanobacteria, as ancient prokaryotes, not only support aquatic ecosystems through photosynthesis but can also form harmful blooms when overproliferated, releasing toxins that threaten drinking water and ecological security.

Most existing algal bloom warning systems are based on “post-event monitoring”, relying on indicators such as chlorophyll and phycocyanin to issue alerts only after blooms have occurred. Machine learning predictions are limited by regional data and are difficult to generalize, while molecular detection methods cannot simultaneously cover multiple species due to primer specificity. More importantly, these methods fail to mechanistically explain why certain cyanobacteria still dominate and even produce toxins in phosphorus-deficient waters.

Phosphorus is the most critical “limiting element” for cyanobacterial growth. Previous studies have shown that phosphorus limitation alters algal species composition and can even promote the proliferation of certain non-nitrogen-fixing cyanobacteria, leading to toxin production. Cyanobacteria have also developed adaptive mechanisms, such as high-affinity phosphate transport systems, and even “streamlined genomes” to enhance survival efficiency. But how small a genome must be to indicate lower risk? What are the underlying metabolic mechanisms?

The research team collected metagenomic data from a large-scale water transfer canal with long-term phosphorus levels below 0.02 mg/L and reconstructed 317 cyanobacterial genomes. They discovered a clear “genome size–ecological function” differentiation pattern: cyanobacteria with genomes smaller than 3 Mbp (megabase pairs) are “streamlined types”. They dominate in phosphorus-deficient environments, excel in phosphorus uptake, light capture, and carbon fixation, rarely produce toxins, and act as “low-risk workers” in the system. In contrast, those with genomes larger than 3 Mbp are “complex types”. They carry toxin genes and buoyancy regulation genes, which under certain conditions can trigger blooms and release harmful substances such as microcystins, making them “high-risk groups”.

Moreover, these small-genome cyanobacteria exhibit distinct seasonal succession: Synechococcus dominates in spring, while Cyanobium takes over in autumn, reflecting niche differentiation driven by temperature and light variations.

Based on this discovery, the study proposes using “~3 Mbp” as a threshold to establish a genome size-oriented proxy indicator for cyanobacterial risk early warning. If the proportion of cyanobacterial genomes larger than 3 Mbp increases, the system could initiate preventive measures in advance, achieving a critical shift from “responding after blooms occur” to “preventing blooms before they happen”.

This research not only reveals the genomic evolutionary strategies of cyanobacteria in adversity but also advances algal risk monitoring from reactive to preventive approaches. It provides a replicable paradigm for sustainable algal control in global artificial freshwater networks.

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Journal

Science Bulletin

DOI

10.1016/j.scib.2025.11.005 

Method of Research

Experimental study

 

From science fiction to tumor-fighting reality: are injectable nanorobots on the way?

Science China Press

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Inspired by how a car uses an engine and a steering wheel to reach its destination, the nanorobot integrates two enzymatic functions. Urease works for propulsion by harnessing endogenous urea in bloodstream and tumor microenvironments, while catalase controls orientation by sensing the H2O2 concentration gradient typically existing in tumor microenvironments. By decoupling propulsion and orientation, the nanorobot exhibits ultrasensitive chemotaxis under physiological conditions. After intravenous injection, the nanorobots achieve significantly enhanced tumor-targeting efficiency and improved antitumor efficacy.

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Credit: ©Science China Press

In 2021, Science posed a century-defining question for nanomedicine: Will injectable, disease-fighting nanobots ever be a reality? Recently, Guan’s group from Wuhan University of Technology (China) provided a compelling answer by reporting an injectable nanorobot for precision cancer therapy. This study, entitled “Bienzyme-powered nanorobots with ultrasensitive chemotaxis for precision cancer therapy” was published in National Science Review and offers direct and affirmative evidence addressing the question raised by Science.

Inspired by automobiles combining an engine and a steering wheel, they reported nanorobots integrating two kinds of enzymes with distinct functionalities to control propulsion and orientation. Specifically, they integrated catalase and urease onto the same hemispheres of Au nanoparticles to develop Janus nanorobots. Urease works for propulsion by harnessing endogenous urea in bloodstream and tumor microenvironments, while catalase controls orientation by sensing the H2O2 concentration gradient typically existing in tumor microenvironments. With the synergistic effects of these two enzymatic reaction systems, propulsion and orientation are decoupled in nanorobots, offering significantly enhanced chemotactic sensitivity toward tumor-specific biomarkers H2O2.

After intravenous administration into a tumor-bearing mouse model, these nanorobots achieved high targeting efficiency, deep penetration, and significant cell internalization. Compared with the passively diffused counterparts, their tumor-targeting efficiency, penetration depth, and cell internalization were improved by 209, >10, and 1970 times, respectively. When loaded with antitumor drugs, they boost the tumor suppression efficacy by approximately 49 times compared with the passive counterparts.

This propulsion-enhanced chemotaxis strategy reported in this work is broadly applicable for diverse chemotactic nanorobot systems by tailoring the combinations of chemical reaction systems. In the future, the same strategy could be extended to the treatment of inflammation, infection, and other diseases characterized by localized biochemical gradients.

To promote clinical translation, Guan’s group has established a company dedicated to advancing injectable nanorobots toward medical applications. With continued optimization, rigorous evaluation, and interdisciplinary collaboration, the researchers anticipate that injectable nanorobots can move from experimental models to clinical practice in the foreseeable future, offering new hope for patients facing cancer and other challenging diseases.

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Journal

National Science Review

DOI

10.1093/nsr/nwaf580 

Method of Research

Experimental study

 

Increased deciduous tree dominance reduces wildfire carbon losses in boreal forests

New research published this week shows that when forests shift from mostly coniferous to mostly deciduous, they could release substantially less carbon when they burn.

Northern Arizona University

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As climate change drives more frequent and severe wildfires across boreal forests in Alaska and northwestern Canada, scientists are asking a critical question: Will these ecosystems continue to store carbon or become a growing source of carbon emissions? New research published this week shows that when forests shift from coniferous—consisting mostly of pines, spruces and larches—to deciduous—consisting mostly of birches and aspens—they could release substantially less carbon when they burn.

The National Science Foundation-funded study, led by researchers from the Center for Ecosystem Science and Society (ECOSS) at Northern Arizona University and published in Nature Climate Change, found that boreal forests dominated by deciduous species lose less than half as much carbon per unit area burned compared to historically dominant black spruce forests. Even under severe fire weather conditions, carbon losses in deciduous stands were consistently lower than those in conifer forests.

“This work shows that not all boreal forests burn the same way,” said Betsy Black, who led the study as part of her master’s thesis research at NAU. “As deciduous trees become more common after fire, they can fundamentally change how much carbon is lost to the atmosphere during future wildfires.”

Boreal forests store a large fraction of the world’s terrestrial carbon, much of it locked away in thick organic soils that have accumulated over centuries. Historically, these forests have acted as a carbon sink, but warming temperatures have increased fire size, severity, and frequency, raising concerns that boreal ecosystems could shift to releasing more carbon than they store, accelerating climate change.

“Our previous research shows that deciduous forests can accumulate much more carbon after fire than spruce forests,” said Michelle Mack, ECOSS professor and senior author on the study. “But we were curious about what happens to that carbon when these forests burn. No one had measured that before.”

To answer that question, the team analyzed carbon pools and combustion losses in plots within nearly a dozen large fire scars across Alaska and Yukon. They found that deciduous forests store more carbon aboveground in combustion-resistant tree stems and less in deep organic soils that readily burn, resulting in lower overall carbon emissions during fire.

The study also revealed stark differences in what controls carbon loss between forest types. In conifer forests, emissions were driven primarily by bottom-up factors, such as fuel availability and soil moisture. In contrast, carbon losses in deciduous and mixed forests were more sensitive to fire weather conditions.

“Seeing weather play such a strong role in deciduous forests was surprising, and it suggests that as climate change drives more extreme fire weather, these forests could become more vulnerable in the future,” said Xanthe Walker, ECOSS professor and corresponding author.

Together, the findings suggest that increasing deciduous dominance, which is already widely observed following severe fires in northwestern North America, could help slow the positive feedback between wildfire and climate warming by reducing carbon emissions per unit area burned. By quantifying how much carbon is lost when deciduous forests burn, and identifying the conditions that control those losses, the study provides critical data for improving wildfire and carbon cycle models and forecasting future global carbon dynamics.

Co-authors on the study include Scott Goetz and Logan Berner of the School of Informatics and Computing at Northern Arizona University, along with Brendan Rogers, Winslow Hansen, Anna Talucci, Stefano Potter, and Jacqueline Dean from the Woodwell Climate Research Center and the Cary Institute of Ecosystem Studies. This research was supported by the National Science Foundation, NASA and the Bonanza Creek Long-term Ecological Research Program.

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Journal

Nature Climate Change

DOI

10.1038/s41558-025-02539-z 

Article Title

Increased deciduous tree dominance reduces wildfire carbon losses in boreal forests

Article Publication Date

15-Jan-2026