{"id":4162,"date":"2020-10-23T10:54:05","date_gmt":"2020-10-23T08:54:05","guid":{"rendered":"https:\/\/www.alpha1-deutschland.org\/?p=4162"},"modified":"2024-04-02T13:58:10","modified_gmt":"2024-04-02T11:58:10","slug":"08-2020-leberbeteiligung-bei-alpha-1-antitrypsin-mangel-erste-therapie-option-in-sicht","status":"publish","type":"post","link":"https:\/\/alpha1-deutschland.org\/en\/08-2020-leberbeteiligung-bei-alpha-1-antitrypsin-mangel-erste-therapie-option-in-sicht","title":{"rendered":"08\/2020: Liver involvement in alpha-1 antitrypsin deficiency: First treatment option in sight"},"content":{"rendered":"
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Liver involvement in alpha-1 antitrypsin deficiency: First treatment option in sight<\/span><\/h1>\n<\/div>\n\n\n\n
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Author<\/h4><\/span><\/span>\n<\/div>\n
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Pavel Strnad<\/strong> and members of his team: Moritz Kleinjans, Barbara Burbaum, Samira Amzou<\/p>\n<\/div>\n\n\n\n

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Alpha-1 antitrypsin deficiency can affect many organ systems, most notably the liver and lungs. For lung involvement, augmentation therapy is a proven treatment option because the lungs are primarily damaged by the protein deficiency. The liver is affected by the excess of misfolded alpha-1 antitrypsin. Until now, there have been no therapies for this, apart from liver transplantation as a last resort.<\/p>\n

Thanks to medical and biological advances in recent years, several therapeutic approaches have been developed to correct the excess of misfolded AAT in the liver. One approach focuses on promoting the elimination of the altered protein from the liver, while another aims to inhibit the production of this potentially harmful protein. While there is currently no evidence of efficacy in humans for the first approach, Promising data on the second one were recently published.<\/a> This approach uses a so-called siRNA (small interfering RNA) and therefore does not alter human genetic information, also known as DNA, but acts at a level below. Protein production involves several steps. One of these is the production of an RNA molecule, which represents the working copy of the DNA and is used directly for protein synthesis. With siRNA, the reading of a specific RNA molecule can be prevented: siRNA therapeutics are therefore considered a new secret weapon in the fight against genetically inherited diseases. The first siRNA-based drug was approved in 2018, and another therapeutic followed this year. The first inhibits the production of a mutated protein called transthyretin in the liver, which otherwise leads to congenital transthyretin amyloidosis; the second suppresses enzyme production that leads to acute hepatic porphyria. In both cases, the siRNA is primarily taken up by liver cells.<\/p>\n

Since summer 2019, Arrowhead has been conducting two comparable studies investigating the efficacy of alpha-1 antitrypsin-specific siRNA in patients with liver involvement and severe alpha-1 antitrypsin deficiency. Currently, only Pi*ZZ patients without significant lung involvement are being enrolled in the study; patients with more severe symptoms will be examined at a later date. The first data from these studies were recently published in a press release. The four patients described who have already completed the study were all treated at Aachen University Hospital. Recruitment was carried out in close collaboration with Alpha1 Germany and Alpha-1 Plus Belgium. The investigational drug was administered subcutaneously, directly under the skin, similar to a vaccination or thrombosis injection. Patients received three doses at intervals of four and twelve weeks. A liver biopsy was performed at the beginning of the study and again 24 weeks after the start of therapy, and regular blood tests were also conducted. After 24 weeks, the amount of alpha-1 antitrypsin in the subjects was reduced in both serum (by up to 931 TP3T) and liver (by up to 951 TP3T). In three out of four patients, the amount of already polymerized alpha-1 antitrypsin in the liver was also reduced, with the maximum reduction reaching 971 TP3T. All subjects showed a decrease in the established liver damage markers ALT and GGT. Liver stiffness, used for the non-invasive assessment of liver scarring, decreased in all study participants. No relevant pulmonary side effects were reported, and all patients opted for the offered extension of therapy after completion of the initial 24-week study. Although this is very early clinical data, further development and marketing of the product are already being considered.<\/a><\/p>\n<\/div>\n\n\n\n\n\t\t\t<\/div> \n\t\t<\/div>\n\t<\/div> \n<\/div><\/div>\n\t\t

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\u201d<\/span>After all these years, there is finally a glimmer of hope for patients suffering from liver involvement due to alpha-1 antitrypsin deficiency. <\/p>Univ.-Prof. Pavel Strnad<\/span><\/span><\/div><\/blockquote>\n\t\t<\/div> \n\t<\/div>\n\t<\/div> \n<\/div><\/div>\n\t\t\t<\/div> \n\t\t<\/div>\n\t<\/div> \n<\/div><\/div>\n\t\t

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Professor Pavel Strnad, head of the study, would like to take this opportunity to thank all participants and the patient organizations involved for their outstanding collaboration. After all these years, there is finally a glimmer of hope for patients suffering from liver involvement due to alpha-1 antitrypsin deficiency. Therefore, he and his team would like to make this treatment option available to more people with severe AATD. If you are interested, please contact the familiar telephone hotline (0241-8036606) for further information. This applies particularly to participants with recurrently elevated liver enzymes and a history of liver fibrosis. Unfortunately, patients with liver cirrhosis, aged 65 years or older, or with significant lung involvement (FEV1 \u2264 65%) are currently unable to participate in this study.<\/p>\n

Although the results so far have met or even exceeded our expectations, caution is still advised. Currently, we only have data from the first trial group, which has already completed the study. This group consisted of four participants treated for six months. While it is encouraging to see that there were no measurable deteriorations in lung function during this period, the long-term effects of the therapy on the lungs remain unknown. Therefore, at this time, only those participants for whom liver involvement is the primary concern should take part in the study.<\/p>\n<\/div>\n\n\n\n

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A personal note<\/span><\/h2>\n

Dear Alpha1 families,<\/p>\n

We cordially invite you to our kick-off event, Virtual Children's and Youth Day, on Saturday, October 31, 2020.<\/p>\n

Our speaker:<\/strong> Dr. Eva-Doreen Pfister, Senior Physician at Hannover Medical School specializing in pediatric gastroenterology<\/p>\n

Your topic:<\/strong> Alpha-1 Antitrypsin Deficiency \u2013 2020 Update: Special Features in Childhood and Adolescence<\/p>\n

The topic of nutrition will also be part of the presentation.<\/p>\n<\/div>\n\n\n\n

<\/div><\/div>To the official invitation<\/span><\/a>
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Everyday tip<\/span><\/h2>\n

Uwe Deter, our member, advisor and SHG group leader in Hamburg, sent us the tip to take a look at the following page:<\/p>\n

http:\/\/www.patienten-universitaet.de\/<\/a><\/p>\n

The page of M<\/strong>medical H<\/strong>university H<\/strong>Hannover has a wealth of useful information \u2013 it's worth browsing. The announcement for the 2nd Alpha1 Patient Day will follow shortly. Currently, December 1st, 2020 is reserved for the online seminar \u2013 more information will be available in the next newsletter or on our website in the events calendar.<\/p>\n

Do you have a tip for us? Then write to us at: <\/strong>Erfahrungen@alpha1-deutschland.org<\/strong><\/a><\/p>\n<\/div>\n\n\n\n

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Addendum<\/span><\/h2>\n

In newsletter 7 we reported on lectures at the ELF Patient Day, These have now been published.<\/a><\/p>\n<\/div>\n\n\n\n

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Corona Update<\/span><\/h2>\n

We found some interesting links again this time:<\/p>\n