Article No. 350
18 June 2020
aHUS Global Action‘s blog about “aHUS in Deutschland” revealed an active patient support group for aHUS and MPGN patients. ( See previous article here)
Recently , amid the Coronvirus epidemic lockdown, Sebsthilfegruppe aHUS und MPGN hosted its annual patient day event on line instead of gathering people together at the University of Bonn as in previous years. Their online webinar has been recorded and a video of it is available*. It is delivered in German of course.
( The Patient Group has kindly provided a video file of the presentations to aHUS Global Action which can be found at Item 3 on this page in our Info Centre )
However Oksana Paulsen, a representative from the German group, has written a brief synopsis of the events of the day and what the expert speakers had to tell patients – both those with aHUS and MPGN.
Amongst very the informative talks, the German aHUS experts’ views on “COVID 19 and aHUS“ and some German aHUS patients’ experience of it are very worth noting.
The German aHUS and C3G Patient’s Day held Webinar on June 6, 2020
On June 6, 2020, experts welcomed more than 60 aHUS and C3G (C3 glomerulopathy) patients to a webinar organized by the German self-help group for complement mediated diseases https://www.ahus-selbsthilfe.de/.
Since 2013, German patients have been meeting in Bonn (Germany) for the aHUS/C3G Patient’s Day. The number of attendees was usually between 30 and 40. This year, the online format has attracted even more. If you speak German, you can ask for the record of the webinar via firstname.lastname@example.org.
Prof. Dr. Thorsten Feldkamp (University of Kiel) opened the webinar with a talk explaining what aHUS is and what happens when the complement systems “explodes” triggered by a virus, by giving a birth or other factors. He showed how Eculizumab (Soliris®) blocks C5b-9 (proteins that build aggressive Membrane Attack Complexes – MACs) and why it is important to take it regularly, especially in the times of Corona virus. He stressed that aHUS patients not treated by Eculizumab face a greater risk of developing severe symptoms if infected by Corona. Furthermore, he reported about some cases of aHUS patients in Italy and France who recovered from COVID-19 without greater damage. All of them had been treated with Eculizumab.
Finally, Prof. Feldkamp informed that Ultomiris ( Ravulizumab) – the “better Soliris” administered every eight weeks (if your weight is more than 40 kg) instead of every two weeks – is expected on the European market at the end of 2020. He is confident that German aHUS patients will be able to switch to Ultomiris very quickly. According to Prof. Feldkamp, some studies have shown that Ultomiris provides the same security as Soliris and that the manufacturer is further developing the drug to enable subcutaneous administration instead of IV (intravenous). This will surely considerably improve the patients’ quality of life.
The participants asked a lot of questions using the chat. Some of them were answered by the experts directly in the chat, the most relevant questions were answered after each talk. One of the questions was about coming off dialysis after a severe aHUS outbreak. Prof. Feldkamp reported that an early and regular treatment with Soliris usually leads to a fast improvement of the kidney function and most of the patients do not need dialysis just after some weeks. The person who asked the question had been on dialysis for about three years. His Soliris treatment was interrupted just some weeks after the aHUS outbreak three years ago (obviously because his doctors knew only a little about this rare disease). Unfortunately, in this case the damage is irreparable. The question is, how is such a case possible in a country where the state health insurance provides access to Soliris for all aHUS patients?
The second talk was held by a renowned German immunologist Prof. Dr. Peter Zipfel from the University of Jena. He reported about bio-markers and diagnostic aspects for aHUS and C3 glomerulopathy (C3G, also called MPGN – membrane proliferative glomerulonephritis). Both diseases have similar features: Triggered by a virus of another stressful factor, the immune systems gets over activated and starts to damage the own organs. The reason is mostly the genetic predisposition. However, why some members of the same family with the same genes get ill and the others not? Auto-antibodies and a specific combination of the triggers play an important role in this process.
Professor Zipfel explained extremely complex processes that take place in the complement cascade. The disaster starts with the over-activation of the alternative pathway of our immune system. Usually, this part of our innate immune complex (so, we have it already when we are born) is always activated a little, like a guardian who looks for viruses and bacteria. As soon as it detects an invader, the alternative pathway (the guardian) “wakes” other parts of the immune system who, in turn, bring out “heavy weapons” to kill the enemies by the process of phagocytosis. So, the mechanism is extremely useful for us to stay alive.
When the danger is away, a healthy body has a kind of “brakes” to stop the overactivation of the alternative pathway. These brakes are special proteins called “factors” (Factor B, D and especially important Factor H). In case of absence of some genes that are responsible for the production of these factors, there a no “brakes” for the immune system. In some cases, auto antibodies like C3 nephritis factor or others prevent the brakes to do their job.
Consequently, the convertase of the complements in the immune cascade cannot be stopped, the immune system does not calm and continues the fight even if all enemies are defeated. The immune system damages the own body, in particular the kidneys.
The scientific approach of Peter Zipfel’s research team is the development of proteins that can replace the “factors” and stop the uncontrolled process. However, it will take years until these attempts can result in a drug. Until then, the scientists will have to apply for grants or wait for donations because in Germany, it is not typical for investors to pump huge amounts of money into pharmaceutical research like it is the case in the U.S. Some money comes from non-profit organizations like the Italian “Progetto DDD Onlus”. The German self-help group for complement mediated diseases will help the development, too. So, if you like to make a donation, please visit our website https://www.ahus-selbsthilfe.de/ or contact email@example.com.
Prof. Peter F Zipfel
Prof. Zipfel reported that C3G cannot be treated by now. While aHUS can be kept under control by blocking the complement cascade on the level of C5, in case of C3G, an upper level of the cascade – the level of C3 – is affected. As a result, the kidneys are damaged not so fast like in case of aHUS, but almost all patients need dialysis after some years. Even transplanted kidneys are affected in the same way just a few years after a transplantation, so, some hospitals do not put their C3 patients on the waiting lists for organ donation. However, treatment with Eculizumab helps in 50% of C3G cases to stop the immediate damage on the kidneys by blocking the formation of Membrane Attack Complexes (MACs) on the C5 level. These patients benefit in the same way like aHUS patients from Soliris and can hope to prolong their kidney function until an efficient drug is developed. Unfortunately, since there is no medical approval for Soliris to be used for C3G, these patients have to struggle for getting Soliris in an off-label use, which is almost impossible even in Germany because of the high costs. A solution would be conducting further studies for this approval, which is probably not profitable for the manufacturer in case of such a rare disease like C3G.
After this talk, the members of the German self-help group were able to see each other though their cameras in the break. Some reported their very personal stories and there was a great agreement that more should be done for aHUS and C3G awareness. We need a kind of expert center in Germany consisting of doctors and experienced patients who would help people with aHUS and C3G diagnosis. Not every doctor is able to know each rare disease in detail. So, we need a kind of network so that patients can find the right expert to avoid mistakes in the diagnosis and treatment.
After the break, children nephrologist Dr. Gesa Schalk (Children’s Kidney Center in Bonn) held a talk specially addressed to children and young people. She explained in simple words what happens with their body in case of aHUS and how important regular treatments are. In the discussion with the parents after the talk, she stressed the importance of the meningitis prevention by vaccination and antibiotics. She recommended daily antibiotics prophylaxis (Penicillin) for children under 10 years because their parents have difficulties to distinguish symptoms of meningitis from other illnesses. While meningitis rates in Europe are very low, patients older than 10 do not need antibiotics but have to pay attention to any unwellness and in case of severe head aches of stomach problems immediately see their doctor.
She also gave some advice concerning Corona prevention for children. Her opinion is, considering the low numbers of Corona infections in Germany at the moment, it is ok if children go to school. However, for our kids it is important to be further treated with Soliris, to keep a distance of 1.5 m from other people, to wash their hands and, if necessary, to wear masks. According to Dr. Schalk, we cannot keep our children in isolation for years.
The last talk was presented by the German Alliance for rare diseases (ACHE e.V. https://www.achse-online.de/de/). Its representatives reported about how aHUS and C3G patients can benefit of the funded studies conducted by the Alliance. The organization also represents the interests of people suffering on rare diseases on the political level and has a direct contact to the German Ministry of Health. It was good to see that we are not alone with our rareness.
In the last 30 minutes of the webinar, personal questions from the chat were answered by all experts: aHUS and pregnancy, high correlation of complement mediated diseases with other autoimmune diseases, development of new drugs etc.
The German self-help group for aHUS and C3G thanks to all experts for this valuable meeting! We hope we can meet in person next year, again in Bonn at the beginning of June.
For the record of the webinar please write a short email to firstname.lastname@example.org.
aHUS global Action wish to thank Oksana for taking the time and trouble to produce this synopsis of the Patient Webinar presentations in English and to share it with the global aHUS Community
Also a thank you to Oksana for providing a German translation of the Global aHUS Patients’ Vision
Es wird ein guter Tag sein, wenn ausreichendes Bewusstsein für aHUS/cTMA* es bewirkt, dass sich jeder Patient auf der Welt die richtige Behandlung leisten kann, die er braucht, um geheilt zu werden und wieder normal zu leben
. (*atypisches hämolytisch-urämisches Syndrom / komplementvermittelte thrombotische Mikroangiopathie)