The DZNE, in collaboration with the Dutch company Intravacc, is working on a vaccine for a specific form of Amyotrophic Lateral Sclerosis (ALS). The goal is to optimize a drug prototype developed by DZNE so that it can be tested in patients. ALS is an incurable neurological disease that causes paralysis and usually leads to death within a few years. There are different variants of ALS, some of which are hereditary. The planned vaccine targets the most common genetically caused form of ALS: Unlike in most people, individuals with this variant have an unusually high number of repetitions of a particular DNA sequence in a normally silent section of the C9orf72 gene. This leads to the formation of toxic proteins, particularly long poly-Glycine-Alanine chains. The vaccine aims to trigger the production of antibodies against these proteins in order to neutralize them. This research project is also supported by the EU through an "EIC Transition Grant" worth 2.5 million euros.

Researchers at DZNE and Charité – Universitätsmedizin Berlin have developed an approach to treat NMDA receptor encephalitis more precisely than before: They reprogram white blood cells to target and eliminate disease-causing cells. This method has been successful in lab tests with mice, and clinical studies with humans are currently in the planning stages.

NMDA receptor encephalitis is a severe autoimmune brain inflammation that can lead to memory disorders, epileptic seizures, and psychosis. The condition is triggered by the body’s own antibodies mistakenly attacking the brain. While existing therapies broadly suppress the immune system, this new approach only targets those body cells that produce the problematic antibodies.

The airways are lined with cilia—tiny, hair-like structures that transport foreign particles and mucus out of the lungs. In the rare congenital disorder Primary Ciliary Dyskinesia (PCD), the movement of the cilia is impaired, leading to chronic respiratory infections and progressive lung damage. DZL researchers Dr. Ben Ole Staar and Dr. Laura von Schledorn in Hannover are developing a therapy for PCD. They extract patients’ stem cells, correct them genetically, and differentiate them into basal cells. After integration into the airway epithelium, these cells can form functional cilia. Researchers are currently investigating how to damage the diseased tissue in such a way that space is created for the transplantation of repaired cells—and how many cells are required to achieve effective self-cleaning of the airways.

A balanced gut microbiome supports digestion and offers protection against infections. Researchers at the DZIF at the Helmholtz Centre for Infection Research, led by Dr. Lisa Osbelt-Block and Prof. Till Strowig, have discovered that bacteria of the species Klebsiella oxytoca can displace pathogenic bacteria such as Salmonella and Klebsiella pneumoniae—responsible for around 800,000 deaths annually—from the gut. K. oxytoca competes with these pathogens for nutrients and creates conditions that benefit commensal bacteria. This allows the microbiome to regain its balance. Based on these findings, the team is developing a living biotherapeutic with €2.2 million in DZIF funding. The goal is to create a drug capsule containing freeze-dried K. oxytoca bacteria that could help patients with weakened immune systems and persistent K. pneumoniae colonization in particular. The next step is to test the preparation in an initial clinical study with healthy volunteers to determine its efficacy, tolerability, and safety. The team also plans to spin off the project as a start-up, “Arvalus Therapeutics”.

With a new triple therapy, patients with cystic fibrosis (CF), also known as mucoviscidosis, experience significantly less mucus in their lungs and improved ventilation of their airways. In CF, the gene for an ion channel is altered, resulting in thick mucus that clogs the airways of the lungs and other organs such as the intestines. Recently developed so-called small molecule CFTR modulators make it possible to treat specific causes, including the F508del-CFTR mutation, which is present in about 90% of all CF patients. These modulators activate existing channels and help ensure the proper formation of the CFTR channel. The interim results of the first long-term study show that the therapy with the three CFTR modulators Elexacaftor, Tezacaftor, and Ivacaftor is effective, safe, and well-tolerated in the long term. Both lung function and breathing, as well as the nutritional status of cystic fibrosis patients, improved, and exacerbations—episodes of worsening lung function—occurred less frequently.

Tuberculosis is the leading cause of death worldwide from bacterial infections; people with weakened immune systems and those infected with HIV are particularly at risk. According to the WHO, around 1.6 million people die from tuberculosis each year, especially in Southeast Asia, Africa, and the Western Pacific. A major challenge is the emergence of resistant bacteria, against which only a few antibiotics are effective. The antibiotic candidate BTZ-043, discovered at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute and further developed with the involvement of DZIF, shows promising results against multidrug-resistant strains and received global patent protection in 2023.

In preclinical tests and Phase I studies, BTZ-043 demonstrated good tolerability, safety, and efficacy. Currently, the antibiotic candidate, named Leibniz Drug of the Year in 2023, is being tested in several Phase II clinical studies in different dosages and combinations with other therapies to optimize treatment strategies for drug-resistant tuberculosis.

Targeted radionuclide therapy against prostate-specific membrane antigen (PSMA) has made significant progress in recent years and is now a promising treatment option for patients with advanced prostate cancer. This approach uses radioactively labeled molecules that specifically bind to PSMA, which is found in higher amounts on tumor cells. This allows cancer cells to be precisely irradiated while sparing healthy tissue as much as possible. PSMA is also successfully used in fluorescence-guided surgery: by combining radioactive PSMA-binding substances with fluorescent dyes, tumor tissue can be made visible before and during surgery and removed more accurately. Researchers in the Radiopharmaceutical Development Department at the DKTK partner site in Freiburg are working closely with the Nuclear Medicine Department at the University Medical Center Freiburg to bring such innovative radiopharmaceuticals into clinical practice. In addition to PSMA, a radiopharmaceutical targeting MMP-14—a newly discovered structure on tumor cells—was developed in collaboration with the company Bicycle Therapeutics and has successfully entered clinical testing. This opens new possibilities for the targeted diagnosis and treatment of solid tumors.

More than 90 percent of people are infected with the Epstein-Barr virus (EBV) at some point in their lives. In most cases, the infection occurs during childhood and is typically asymptomatic. However, particularly in the case of later infections, EBV can trigger diseases such as mononucleosis (glandular fever), autoimmune disorders, multiple sclerosis, and various types of cancer. Currently, there is no vaccine available. Supported by DZIF, the start-up EBViously, spun off from Helmholtz Munich, aims to change this: The goal is to bring a promising vaccine candidate from the laboratory into quality-controlled production, thereby paving the way for preclinical and clinical studies. To this end, EBViously will exclusively license patents for the development and use of non-infectious, EBV-derived virus-like particles in humans from Helmholtz Munich.

The active substance dextromethorphan (DXM) is primarily known as a cough suppressant. Research has shown that DXM can also protect pancreatic islet cells and lower blood sugar levels. However, the drug also affects the brain and can cause dizziness and fatigue. Researchers at DZD have modified DXM so that it protects insulin-producing cells and lowers blood sugar without any side effects on the brain. The chemical modifications prevent it from crossing the blood-brain barrier. In mice, the derivative protects pancreatic cells from cell death without affecting their behavior. A U.S. patent has been granted for these derivatives. The modified drug is now being further developed and is considered a promising new candidate for diabetes medications.

A new treatment approach could help prevent severe heart damage after a heart attack. Researchers from University Medical Center Mainz and the DZHK have discovered that an excessive inflammatory response can worsen scarring in the heart and reduce its pumping ability. Their method specifically blocks the signaling pathway responsible for this reaction—with promising results in animal studies. Treated mice developed less scar tissue and showed improved heart function. In November 2024, the European patent EP4247408 was granted for this discovery. The next step is to find an industry partner to further develop the therapy and bring it into clinical use.

A true pioneering achievement was accomplished under the leadership of DZL scientists: The first German-language guideline, "Management of Adult Patients with Bronchiectasis," has been adopted. Bronchiectasis is a condition characterized by the dilation of the bronchi, which is associated with impaired mucus clearance, chronic inflammation, and frequent episodes of infection. In recent years, the previously limited research data has been significantly improved: The DZL-associated Bronchiectasis Registry PROGNOSIS and the European Registry EMBARC collect data and biological materials to better understand this neglected disease. In addition, starting in 2024, DZL will focus on this area. The newly adopted guideline summarizes the current state of research and provides helpful recommendations for clinical practice.

For World AIDS Day 2024, the International Antiviral Society–USA released new guidelines on HIV treatment and prevention. These were developed by an international panel of medical experts, including DZIF scientist Prof. Dr. Clara Lehmann. The guidelines recommend advanced HIV therapies and prevention methods for high-risk groups, such as pre-exposure prophylaxis (PrEP), where HIV-negative individuals take HIV medication to protect themselves from infection. The goal is to tailor treatments to individual needs and improve adherence through long-acting options. A comprehensive approach also includes preventing related conditions, such as cardiovascular disease. Despite progress, global access to HIV treatment and prevention remains unequal. The guidelines therefore emphasize the need for targeted efforts to ensure fair access to life-saving care and to curb the epidemic.

For the first time, a large clinical study has clearly demonstrated that transcranial magnetic stimulation (TMS) is an effective and safe treatment option for individuals experiencing persistent voice hearing. The study, which involved researchers from several DZPG sites, represents an important milestone in schizophrenia treatment. The researchers used continuous theta burst stimulation (cTBS) to stimulate areas of the brain responsible for speech and language comprehension. The three-week study involving 138 adults showed that TMS significantly alleviates the symptoms of auditory hallucinations and is well tolerated. Published in The Lancet Psychiatry, the study opens up the prospect of establishing TMS as part of future guidelines for the treatment of schizophrenia.

The company AVOCET Bio, a spin-off of the German Center for Cardiovascular Research, has received 4.7 million euros from the Agency for Breakthrough Innovations. The team, led by cardiologist Elisabeth Zeisberg from Göttingen, aims to develop therapies against RNA viruses. Their technology is based on the enzyme CRISPR-Cas13. Unlike its more famous relative, CRISPR-Cas9, which cuts DNA, CRISPR-Cas13 cuts RNA molecules. "CRISPR-Cas13 has only been known since 2017. We have been using it in fibrosis research for a long time to shut down gene products in the heart muscle," says Zeisberg. Early in the COVID-19 pandemic, she recognized its potential for combating RNA viruses, such as the coronavirus. AVOCET plans to further develop this method into a platform technology that could lead to therapies for other RNA viruses, such as influenza or rabies, as well as for cancer and heart diseases. The AVOCET example demonstrates how long-standing basic research can lead to application-driven innovations at the right time—even across disciplinary boundaries.

Using innovative, complex AI algorithms, researchers from the DKTK program "Molecular Diagnostics, Early Detection, and Biomarkers" identified specific DNA methylation patterns. These genetic fingerprints serve as the basis for precise predictive models, known as classifiers. They can diagnose tumors with high accuracy and help determine the best treatment strategy. The start-up Heidelberg Epignostix aims to market these classifiers as diagnostic products worldwide. To achieve this, the interdisciplinary expert team is collaborating with leading international cancer research institutions.

The first application is the classification of brain tumors, particularly in children and adolescents. In July 2024, funding was provided for the market launch of the "Brain Tumor Classifier" as an approved "in vitro" diagnostic product. In the future, this technology could be applied to many other oncological challenges.

Viacure GmbH was founded in May 2023 as a spin-off of DZD partner Helmholtz Munich, with the aim of treating type 2 diabetes at its root instead of just combating the symptoms. The company’s work is based on a scientific breakthrough: the discovery of the insulin-inhibiting receptor Inceptor. On this basis, Viacure is developing novel regenerative therapies designed to restore the function of insulin-producing cells. Under the scientific leadership of Prof. Dr. Heiko Lickert, an internationally renowned expert in cell regeneration, the interdisciplinary founding team is pursuing a paradigm shift in diabetes treatment. The vision: a causal therapy that sustainably improves the quality of life of people with type 2 diabetes, while reducing long-term healthcare costs.

The Göttingen-based start-up brainQr Therapeutics, a spin-off of the DZNE, develops active agents for the treatment of brain diseases involving tau proteins. These proteins normally stabilize the molecular framework of nerve cells. However, in Alzheimer’s disease and other “tauopathies”, such as amyotrophic lateral sclerosis (ALS) or progressive supranuclear palsy, these tau proteins detach from the cell framework and clump together. This impairs the mechanical structure of the affected nerve cells to such an extent that they ultimately die. BrainQr Therapeutics is researching low-molecular compounds, also known as “small molecules”, that are designed to preserve the normal state of tau proteins and counteract neurodegeneration. The company is supported by the Federal Agency for Breakthrough Innovation (SPRIND), among others. Its founder and CEO is Prof. Dr. Markus Zweckstetter.

In Molecular Tumor Boards (MTBs), expert teams from various disciplines (oncology, pathology, human genetics, molecular biology, bioinformatics) discuss individual cancer cases and decide on the best treatment option based on the molecular characteristics of the patient's disease. These meetings have evolved with technological advancements and our growing understanding of cancer development. Increasingly, patients and their representatives are being involved in the decision-making processes. The DKTK has been a pioneer in establishing MTB in Germany: Several locations set up MTBs early on, and the MASTER program established the first cross-site MTB. Furthermore, the DKTK is supporting the MTB Alliance project, which aims to further improve the joint scientific and clinical use of MTB data across all DKTK partner locations.

The Digital Mental Health infrastructure, as a network of experts, is advancing methods for capturing mood, movement, and other everyday data via smartphones and wearables. The research findings generated from these data on mechanisms and risk factors are then used to develop digital health applications for the diagnosis and treatment of mental health conditions that can be directly used in people's everyday lives. To support this translation, the infrastructure provides consulting on the use of digital platforms, automated real-time data analysis, and the development of health applications in accordance with the EU Medical Device Regulation. This aims to accelerate the introduction of new digital innovations, strengthen the international competitiveness of research in the field of Digital Mental Health, and improve the quality of care.

The INFORM program at the DKFZ helps improve survival rates for children and adolescents with cancer. INFORM (INdividualized therapy FOr high-Risk childhood Malignancies) is the world's largest and fastest molecular diagnostics program in pediatric oncology, led by the Hopp Children's Cancer Center Heidelberg (KiTZ). It enables patients with a relapse or high-risk disease to undergo molecular genetic cancer analysis. Since 2015, more than 3,500 tumor samples from 13 countries have been sent to Heidelberg. There, the molecular “fingerprint” of the tumor is classified, searched for therapeutic targets, and the results are discussed with the treating physicians. To date, this has been financed primarily through project funding and private donations. The DKTK has also supported molecular diagnostics for INFORM for many years and funded an accompanying project. An important step was taken at the beginning of 2023: a selective contract now regulates the reimbursement of costs by 73 statutory health insurance companies. Others are expected to follow.

Obesity is one of the most significant risk factors for type 2 diabetes and cardiovascular diseases. Polyagonists can reduce body weight to an extent previously unattainable and improve blood sugar levels. This new class of drugs mimics the effects of several hormones. Polyagonists reduce appetite, enhance feelings of fullness, and promote fat breakdown and insulin secretion. The innovative mechanism was developed by researchers from the DZD and Helmholtz Munich. The first representative of this new drug class has already been approved for the treatment of type 2 diabetes. The medication combines the hormones GLP-1 (Glucagon-like Peptide-1) and GIP (Glucose-dependent insulinotropic Polypeptide). These hormones trigger increased insulin release and suppress appetite. The results are impressive: Depending on the patient group, the new drug reduces body weight by up to 22 percent on average and improves blood sugar levels.

An insufficiently closing mitral valve often leads to shortness of breath and reduced physical capacity. In Germany, about one million people suffer from treatable mitral valve insufficiency, but open-heart valve replacement is too risky for many patients—especially older ones. Prof. Georg Lutter from the DZHK site in Kiel, with support from DZHK, has developed an innovative stent that can be inserted minimally invasively while the heart is still beating.

What’s special: The procedure is performed without general anesthesia and without open-heart surgery. The stent is inserted through a small incision in the chest and precisely positioned under ultrasound and X-ray control. The procedure lasts about 1.5 hours and significantly improves the function of the mitral valve. The "Tendyne" stent, which has successfully treated nearly 2,000 people, is the result of years of research. Since 2020, it has been approved in Europe (CE marking) for high-risk patients.

People aged 50 to 75 who smoke or used to smoke have an increased risk of developing lung cancer. They can now undergo low-dose computed tomography (CT) for early detection. Germany’s Federal Ministry for the Environment, which is responsible for radiation protection, has approved the use of this procedure. This approval is the result of several studies, including contributions from the DZL, which confirmed that lung cancer screening in high-risk groups can detect cancer early. Early detection improves the chances of recovery and helps reduce mortality. Whether this screening will be included in the benefits covered by statutory health insurance will be decided by the Federal Joint Committee, which is responsible for such decisions.

Phenylketonuria (PKU) is a rare metabolic disorder in which the amino acid phenylalanine cannot be sufficiently broken down. Without treatment, it leads to severe neurological damage. Until now, a strict low-phenylalanine diet was considered the standard therapy.

However, with the Europe-wide approval of sepiapterin in June 2025, a drug is now available for the first time that can reduce the burden of disease for those affected. In the APHENITY approval study, in which the DZKJ site in Hamburg also participated, sepiapterin reduced blood phenylalanine concentrations by an average of 63 percent. The effects were even more pronounced in the most severe form of the disease, classic PKU (cPKU). The drug was also well tolerated, proving to be an effective new therapeutic option. The study results were published in The Lancet.

When the heart muscle thickens, the risk of atrial fibrillation, stroke, or heart failure increases. There is a great need to improve medical care for people with hypertrophic obstructive cardiomyopathy (HOCM), as this hereditary heart muscle disease is chronic and worsens over time. In collaboration with Bristol Myers Squibb, the DZHK is taking an important translational step: The pharmaceutical company contributes its experience in drug development, while the DZHK provides real-world data via the TORCH Plus registry. Researchers observe HOCM patients who have been prescribed a new drug. Unlike in a clinical trial, they can evaluate the drug’s effects, interactions with other drugs, and tolerability in a practical setting—and tailor the treatment to each individual patient.