Hereditary lung and liver disease successfully treated for the first time using gene correction
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Alpha-1 antitrypsin deficiency (AATM) is a congenital metabolic disorder. It is caused by a genetic defect, which results in the protective protein alpha-1 antitrypsin (AAT) being produced incorrectly. This deficiency primarily damages the lungs and the liver, where it can lead to serious conditions such as pulmonary emphysema, liver fibrosis or cirrhosis. In particularly severe cases, an organ transplant is the last resort. There is as yet no curative treatment.
A team from the Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology and the Department of Pneumology and Infectious Diseases at Hanover Medical School (MHH), in collaboration with Renji Hospital in Shanghai, China, has now succeeded for the first time in correcting the underlying genetic defect and treating seven patients with AATM.
Using CRISPR/Cas9 technology—known as "gene scissors"—and a biotechnological tool, the researchers specifically modified a tiny defective building block in the genetic material of the AAT-producing liver cells. In technical terms, this procedure is known as base editing. The initial findings on the safety and efficacy of this gene correction have been published in the Journal of Hepatology.
Cell launches its own repair program
Alpha-1 antitrypsin is mainly produced in the liver and travels via the blood to the lungs, where it protects the tissue from being broken down by the body's own enzymes. "Like most congenital genetic disorders, alpha-1 antitrypsin deficiency is caused by a single tiny building block in the DNA—known as a base—being incorrectly incorporated," explains Dr. Michael Ott, senior consultant at the Department of Gastroenterology and head of the Laboratory for Cell and Gene Therapy.
In many gene therapies, an intact, functional copy of the defective gene is introduced into the cell, for example using special viral vectors. This is intended to restore the missing or impaired protein production. The MHH researchers are taking a different approach. They are focusing on the mutation itself.
What makes this gene repair method unique is that, following the modification of the mutated base, a single-strand break is created on the opposite strand. The cell then automatically initiates its natural repair program and incorporates the correct counterpart into the second strand as well. As a result, the mutation disappears without a double-strand break occurring in the DNA.
"We tested this approach on other conditions in animal trials for a long time, until, thanks to a long-standing collaboration with Renji Hospital in Shanghai, we were able to conduct a joint clinical trial there," says Dr. Simon Krooss, a doctor and scientist at the Department of Gastroenterology. As the condition occurs primarily in Europe and the U.S., but is rare in Asia, the MHH sent seven patients, accompanied by medical staff, to Shanghai. The costs were covered by a Chinese company that is developing the base-editing method.
The condition is often overlooked
One of those affected is Katrin H. The 55-year-old had been suffering from shortness of breath for years and was becoming increasingly unable to cope with physical exertion. As a result, she had to give up her job as an anesthesiologist. "The symptoms are usually nonspecific, which is why the condition is often diagnosed late," says Dr. Nora Drick, an associate professor at the Department of Respiratory Medicine. "The condition is often initially mistaken for bronchial asthma."
H. was then diagnosed with AATM at the MHH in 2011. As the patient with the most severe form of this genetic defect, in which the body no longer produces any functional protective protein at all, she received what is known as augmentation therapy. This involves administering the missing protein into the body via a vein—every week, for the rest of her life. "However, the treatment had little effect; the disease continued to progress slowly but inexorably," says H. At the start of 2026, she learned about the trial and was certain: "This is my chance."
Clinical trial planned at MHH
In March, the 55-year-old flew to Shanghai, accompanied by Ott. She stayed there 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 AAT and the side effects were nonexistent. She has not needed augmentation therapy since then. "For me, it's like winning the lottery," says a delighted H.
Although the gene therapy cannot reverse the damage to her lungs and liver that had already occurred, the patient can now hope that her condition has been halted and will not deteriorate further. The Hannover resident can therefore continue in her office job in the field of hospital hygiene.
In the future, flights to Shanghai will no longer be necessary for AATM patients to benefit from this therapy, which has not yet been authorized. The clinical trial at the MHH is set to continue in early 2027. And the procedure is not limited to AATM, a condition that affects an estimated 120,000 people in Europe. "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," emphasizes Ott.
More information
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
Key medical concepts
Alpha-1 Antitrypsin DeficiencyEditing, Basealpha 1-Antitrypsin
Clinical categories
Pulmonary medicineGastroenterologyClinical genetics Provided by Hannover Medical School Who's behind this story?
Lisa Lock
BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →
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