"Revolutionary turning point in gene therapy"
Researchers develop system for the targeted treatment of individual organs
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Gene therapies - like many other highly effective drugs - spread throughout the bloodstream after administration. In order to reach the actual target organ sufficiently, very high doses often have to be used. This frequently leads to considerable side effects and often makes the treatment extremely expensive.
A research team at Charité's German Heart Center (DHZC) has now developed a method that allows gene therapy to be applied in high concentrations in a single organ for the first time - and has impressively demonstrated this in an animal model.
The work, which has now been published in "JACC: Basic to Translational Science", shows that this concept could improve the treatment of genetic diseases: This concept could fundamentally change the treatment of genetic diseases in the future.
In the accompanying editorial of the issue of the journal entitled: "A Revolutionizing Turn in Gene Delivery", Prof. Atta Behfar, cardiologist at the Mayo Clinic in Rochester/USA, describes the technology developed at the DHZC as a "potential game changer for the application of novel therapies": "Emmert et al. have presented a platform that bridges the gap between the promise of gene therapy and its precise delivery. [This heralds a new era of organ-specific interventions."
Limitations of gene therapy to date
In conventional, systemically administered gene therapy, the so-called vector - a "gene transporter" so to speak - travels through the bloodstream into the entire body to reach the target organ. It docks onto cells, is taken up by them and introduces an additional or "repaired" gene into the cell.
However, many of these vectors often accumulate primarily in the liver and spleen instead of reaching the actual diseased organ. If the gene therapy is to be effective, correspondingly high doses are required - associated with high therapy costs and, above all, a significantly increased risk of side effects, which often severely impairs the safety of the therapy.
A new approach: treating only the target organ
In cooperation with the Swiss biotechnology company DiNAQOR, the research team at Charité's German Heart Center led by heart surgeon Prof. Maximilian Emmert has therefore developed a catheter-based "closed-loop perfusion system" that is based on the principles and function of heart-lung machines: Using two specially developed balloon perfusion catheters, the kidney was briefly separated from the systemic circulation as part of the study and supplied with oxygen-rich blood in its own "mini blood circuit". The gene therapy vectors were then only introduced into this closed circuit.
Impressive effects
A vector concentration up to 69,000 times higher than in the rest of the body was measured in the isolated kidney circuit. The kidney cells absorbed the "gene transporters" up to 75 times more than with conventional intravenous administration - while other organs such as the liver or spleen were almost not affected at all.
"We were able to show that a single organ in the living organism can be targeted very precisely and highly effectively - without the risks of systemic distribution," says Maximilian Emmert. "This opens up new perspectives for gene therapies, but also for many other active substances such as chemotherapies or antibodies, which could be concentrated locally and at the same time administered much more gently for the rest of the body."
The study also shows that the principle can be transferred to other organs such as the heart, lungs or liver in the long term, says Emmert.
Prof. Volkmar Falk, Medical Director of the DHZC, adds: "The selective perfusion of an organ while maintaining organ function was previously only possible outside the body. The new platform now opens up completely new treatment options in the field of precision medicine."
Perspective
Patients with genetic kidney diseases such as autosomal dominant cystic kidney disease (ADPKD), which experts estimate affects around 50,000 people in Germany, could benefit in particular. Alport syndrome, another inherited and serious kidney disease, also affects several thousand people in Germany.
Further preclinical and clinical studies are required before the method can be used in humans - however, the researchers at the DHZC see this method as an encouraging approach for significant progress in the treatment of genetic diseases.
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
Original publication
Maximilian Y. Emmert, Johannes Holzmeister, Ole Blank, Heike Meyborg, Anne Jomard, Giulia Mearini, Maria Vono, Miriam Weisskopf, Marco Michalski, Chandan Kadur Nagaraju, Mark Dehdashtian, Dominic Hollamby, Chris Rusconi, Steven Zelenkofske, Volkmar Falk, Eduard Ayuso, Josef El Andari, Nikola Cesarovic; "Next-Generation Percutaneous Catheter–Based Closed-Loop Perfusion Concept Enables High-Precision Organ Delivery of Advanced Therapies"; JACC: Basic to Translational Science, Volume 10
Atta Behfar, Zhang Bin, Yalamuri Suraj; "A Revolutionizing Turn in Gene Delivery"; JACC: Basic to Translational Science, Volume 10
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Topic world Gene therapy
Genetic diseases once considered untreatable are now at the center of innovative therapeutic approaches. Research and development of gene therapies in biotech and pharma aim to directly correct or replace defective or missing genes to combat disease at the molecular level. This revolutionary approach promises not only to treat symptoms, but to eliminate the cause of the disease itself.
Topic world Gene therapy
Genetic diseases once considered untreatable are now at the center of innovative therapeutic approaches. Research and development of gene therapies in biotech and pharma aim to directly correct or replace defective or missing genes to combat disease at the molecular level. This revolutionary approach promises not only to treat symptoms, but to eliminate the cause of the disease itself.