HANOVER — Researchers in Germany and China have, for the first time, treated patients with alpha-1 antitrypsin deficiency by correcting the faulty gene inside the body, according to findings published in the Journal of Hepatology and reported on November 2, 2026. Seven patients took part in the early trial, and the first detailed results describe precise correction of the disease-causing gene in liver cells, with the body resuming production of the protective protein it had been unable to make properly.
Alpha-1 antitrypsin deficiency, often shortened to AATM, is a congenital metabolic disorder that can damage both the lungs and the liver. The protective protein alpha-1 antitrypsin is mainly made in the liver and travels through the blood to the lungs, where it shields lung tissue from being broken down by the body's own enzymes. When the protein is produced incorrectly, that protection fails. Over time, patients can develop pulmonary emphysema, liver fibrosis or cirrhosis, and in particularly severe cases an organ transplant becomes the last resort. Until now, there has been no curative treatment.
The new approach does not add a replacement copy of the gene, as many gene therapies do. Instead, it repairs the mutation itself, changing a single incorrectly incorporated DNA building block — a base — in the genetic material of the liver cells that produce the protein. The technique, known as base editing, builds on CRISPR/Cas9 technology, often called "gene scissors," combined with a biotechnological tool developed for the trial.
Illustration: Scientists in a genetics laboratory working on liver cell gene correction.
What Happened
A team from Hanover Medical School (MHH) in Germany, working with Renji Hospital in Shanghai, China, treated seven patients with alpha-1 antitrypsin deficiency using in vivo base editing — meaning the gene correction was carried out inside the patient's body rather than in cells removed and returned later. The initial findings on safety and efficacy were published as a paper by Simon Alexander Krooss and colleagues in the Journal of Hepatology, titled "Liver biopsy confirms precise and efficient correction of SERPINA1 after in vivo Base Editing in a Patient with Alpha-1 Antitrypsin Deficiency."
SERPINA1 is the gene that carries the instructions for alpha-1 antitrypsin. In patients with the deficiency, a single base in that gene is wrong, so the protein it produces does not work as it should. The researchers targeted that exact error. After the defective base was modified, a single-strand break was created on the opposite strand of DNA. The cell then launched its own natural repair programme and inserted the correct counterpart into the second strand as well. As a result, the mutation disappeared without a double-strand break occurring in the DNA — a distinction the researchers highlight, because avoiding a double-strand break is intended to make the editing process more precise and controlled.
The trial grew out of a long-standing collaboration between Hanover and Renji Hospital. Because the condition occurs primarily in Europe and the United States but is rare in Asia, the seven patients were sent to Shanghai accompanied by medical staff. The costs were covered by a Chinese company that is developing the base-editing method, according to the report. The researchers said they had tested the approach in animal trials for a long time before moving to patients.
One of the patients described in the report is Katrin H., a 55-year-old from Hanover who had suffered from shortness of breath for years and had become increasingly unable to cope with physical exertion, eventually giving up her job as an anaesthesiologist. She was diagnosed with alpha-1 antitrypsin deficiency at Hanover Medical School in 2011. As the patient with the most severe form of the defect — in which the body produces no functional protective protein at all — she received augmentation therapy, in which the missing protein is infused into the body through a vein every week for life. The treatment, she said, had little effect, and the disease continued to progress slowly.
In March, Katrin H. flew to Shanghai accompanied by Dr. Michael Ott, senior consultant at Hanover's Department of Gastroenterology and head of its Laboratory for Cell and Gene Therapy. She stayed for four weeks and received an infusion of the new gene therapy drug. Subsequent blood tests showed that her body was once again producing functional alpha-1 antitrypsin, and she reported no side effects. She has not needed augmentation therapy since then. "For me, it's like winning the lottery," she said.
Background
Alpha-1 antitrypsin deficiency is often overlooked, in part because its symptoms are usually nonspecific. Shortness of breath and reduced exercise tolerance can easily be mistaken for other conditions. "The condition is often initially mistaken for bronchial asthma," said Dr. Nora Drick, an associate professor at Hanover's Department of Respiratory Medicine. That diagnostic confusion means many patients are identified late, after lung or liver damage has already advanced.
The biology of the disease explains why a single-letter correction could matter so much. Most congenital genetic disorders of this kind are caused by one tiny building block in the DNA being incorrectly incorporated, Dr. Ott explained. In alpha-1 antitrypsin deficiency, that error sits in the gene for a protein whose job is protection: it guards lung tissue against enzymes that would otherwise break it down. When the protein is missing or faulty, the lungs lose that shield, while abnormal protein can also accumulate in the liver, contributing to fibrosis and cirrhosis.
Existing care has therefore been management rather than cure. Augmentation therapy replaces the missing protein through regular intravenous infusions, but it must continue for life and does not fix the underlying genetic defect. For patients whose disease progresses despite such care, transplantation of a lung or liver may eventually be the only remaining option. That is why a treatment that addresses the root cause — the mutated gene itself — has been a long-sought goal, and why the researchers describe the new results as a first.
Illustration: A healthy liver and lungs protected by protein molecules travelling through the blood.
Base editing differs in an important way from the gene-therapy approaches most readers may have heard of. In many of those therapies, an intact, functional copy of the defective gene is introduced into the cell, for example using special viral vectors, with the aim of restoring the missing protein. The Hanover approach instead focuses on the mutation itself, correcting the faulty base in place. The researchers argue that this direct repair, completed through the cell's own repair programme after a single-strand break, offers a more targeted route — although, as with any first-in-human technique, the long-term safety picture will depend on much larger and longer studies.
The condition affects an estimated 120,000 people in Europe, according to the report. That figure underscores both the size of the unmet need and the limits of the current evidence: seven treated patients and a first published liver-biopsy result are a promising start, not yet proof that the therapy will work safely and durably for everyone with the condition. The published paper's focus on biopsy-confirmed correction in a patient is significant precisely because it shows the edit happened where it was intended — in the liver cells that make the protein — and did so efficiently and precisely.
Why It Matters
If the results hold up in larger trials, base editing could change the outlook for people with alpha-1 antitrypsin deficiency from lifelong management to a one-time correction of the underlying defect. For patients like Katrin H., the immediate difference is already tangible: weekly infusions stopped, functional protein returned, and she has been able to continue in an office job in hospital hygiene. The researchers are careful, however, to note what the therapy cannot do. It cannot reverse damage to the lungs and liver that has already occurred. Its hope, for now, is that the condition has been halted and will not deteriorate further.
The implications may reach beyond this one disease. Dr. Ott emphasised that the procedure is not limited to alpha-1 antitrypsin deficiency. "In the long term, this revolutionary approach can be applied to the treatment of other congenital genetic liver diseases where a single base in the DNA needs to be replaced," he said. Many inherited liver disorders are caused by single-base errors, and a platform that can correct such an error in vivo — inside the body, in the organ where the protein is made — could, in principle, be adapted to them. That prospect is one reason the trial is being watched beyond the relatively small community of alpha-1 specialists.
There are also practical implications for how such therapies are developed and delivered. The trial required patients to travel from Germany to China because the condition is rare in Asia and the collaboration and the developing company were based there. Future trials will test whether the same approach can be delivered closer to where patients live. The researchers said that in the future, flights to Shanghai will no longer be necessary for patients to benefit from the therapy — a statement that points to the planned Hanover trial as the next step toward making the treatment more accessible, if it proves safe and effective.
At the same time, the report is a reminder of how early this science remains. The therapy has not yet been authorised, and the published findings are described as initial results on safety and efficacy. Regulatory approval would require substantially more evidence, including data from more patients, longer follow-up, and careful monitoring for any unintended genetic changes or late side effects. Patients and families should therefore read the new results as a milestone in research, not as an available treatment. This article reports research findings and is general information, not medical advice; anyone with alpha-1 antitrypsin deficiency should discuss treatment options with their own clinician.
What Happens Next
The clinical trial at Hanover Medical School is set to continue in early 2027, bringing the base-editing approach to the institution where many of the patients were diagnosed and followed. That trial will be a key test: it will need to show that the correction can be reproduced in more patients, that functional protein production is sustained, and that the safety profile observed so far holds up over a longer period.
Researchers will also be watching for durability. A one-time gene correction is only valuable if the corrected liver cells keep producing functional protein and the disease truly stops progressing. Follow-up of the seven patients treated in Shanghai — including lung function, liver health and protein levels over months and years — will provide the first answers. The confirmatory evidence that regulators will eventually require is likely to come from controlled trials with defined endpoints, rather than from individual patient stories, however encouraging those stories are.
Broader questions will follow. If base editing proves safe for alpha-1 antitrypsin deficiency, research groups are likely to explore its use in other single-base liver diseases, as Dr. Ott suggested. Manufacturing, cost and access will also matter: a therapy developed with company funding and delivered through an international collaboration will need a pathway to routine clinical use that does not depend on patients travelling across continents. The planned Hanover trial is a step in that direction.
For now, the field has a concrete first: a hereditary lung and liver disease treated by correcting its genetic cause inside the body, with biopsy evidence that the correction was precise and efficient. That is a narrow claim, but a meaningful one — and, for the seven patients who took part, a potentially life-changing one.
Illustration: CRISPR base editing correcting a single DNA letter inside a liver cell.
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FAQ
What is alpha-1 antitrypsin deficiency?
It is a congenital metabolic disorder in which the protective protein alpha-1 antitrypsin is produced incorrectly because of a genetic defect. The deficiency primarily damages the lungs and the liver, and can lead to pulmonary emphysema, liver fibrosis or cirrhosis.
How does base editing differ from other gene therapies?
Many gene therapies introduce an intact copy of a defective gene into the cell. Base editing instead corrects the faulty DNA base itself, in this case in the liver cells that produce alpha-1 antitrypsin, using the cell's own repair programme after a single-strand break.
How many patients were treated in this trial?
Seven patients with alpha-1 antitrypsin deficiency were treated in the joint Hanover Medical School and Renji Hospital trial in Shanghai, with initial safety and efficacy findings published in the Journal of Hepatology.
Can the therapy reverse existing lung or liver damage?
No. The researchers state that the gene therapy cannot reverse damage that has already occurred. The hope for treated patients is that the condition has been halted and will not deteriorate further.
Is this treatment available to patients now?
No. The therapy has not yet been authorised. A clinical trial at Hanover Medical School is set to continue in early 2027, and larger, longer studies will be needed before any regulatory approval.
Sources
- MedicalXpress, "Hereditary lung and liver disease successfully treated for the first time using gene correction," November 2, 2026.
- Simon Alexander Krooss et al., "Liver biopsy confirms precise and efficient correction of SERPINA1 after in vivo Base Editing in a Patient with Alpha-1 Antitrypsin Deficiency," Journal of Hepatology (2026), DOI: 10.1016/j.jhep.2026.09.028.
- Hanover Medical School and Renji Hospital, Shanghai, trial reporting via MedicalXpress, November 2, 2026.
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