11.05.2023 — 

Gene identified and new therapy developed for young patient with rare disease: Dr. Lena-Luise Becker receives Dr. Holger Müller Preis 2022

Esslingen. A decisive contribution to the research and therapy of rare vascular diseases was made by Dr. Lena-Luise Becker, assistant physician at the Charité – Universitätsmedizin Berlin. For her work “Interferon receptor dysfunction in a child with malignant atrophic papulosis and CNS involvement”[1] she was awarded the Dr. Holger Müller Preis 2022 on May 11, 2023 in a ceremony in the Schickhardthalle in the Old Town Hall in Esslingen.
The prize, endowed with 5,000 euros, honors outstanding scientists in the field of rare diseases.

 

Her article, which appeared in the prestigious journal The Lancet Neurology in August 2022, is about her work on Kohlmeier-Degos disease, also called Benign Atrophic Papulosis. This is a very rare vascular disease. Fewer than 100 people are known to be affected worldwide. Changes in the skin are characteristic of this disease. However, internal organs can also be affected. In this case, the disease is called Malignant Atrophic Papulosis (MAP). In patients with MAP, the disease progresses rapidly and is usually fatal within two years.[2] Until now, neither the cause nor an effective therapy to stop the progression had been known.

At Charité – Universitätsmedizin Berlin in 2019, a 9-year-old patient with MAP presented with progressive muscle paralysis in her arms and legs, epilepsy, and severe hearing and vision impairment. Previous attempts at therapy had failed to halt the disease.

Gemeinsam mit ihrem Forschungsteam der Charité – Universitätsmedizin Berlin und der Universität Greifswald sowie mit weiteren Kolleginnen und Kollegen verschiedener Fachrichtungen führte Dr. Lena-Luise Becker zunächst eine ausführliche DNA-Analyse bei der Patientin mit MAP sowie ihren Eltern durch, um die Krankheitsursache herauszufinden.

“Comprehensive diagnostics and, in particular, detailed genetic testing, even beyond the usual approach for the clinical picture” is crucial for Dr. Lena-Luise Becker in terms of general research into rare diseases. The work in the interdisciplinary team of clinical specialists and basic researchers was also a decisive key for her “to find out the causes of this rare disease and ultimately to help the girl”.

During DNA analysis, the research team identified an unknown gene mutation in the interferon receptor. Interferons and other messenger substances produced by the body during immune system reactions, such as to a viral infection, bind to this receptor.[3]

The discovered gene mutation caused an excessive immune response that led to the damage in the patient’s brain. Based on these findings, the team now researched a targeted therapy.

Treatment with a drug that partially suppresses the overactive immune response led to a short-term stabilization of the health condition. The additional administration of a preparation that directly inhibits the interferon receptor finally caused complete neurological stabilization as well as normalization of the immune response.

With their study, the researchers led by Dr. Lena-Luise Becker succeeded in showing for the first time that MAP can be triggered by a gene variant and that this leads to an excessive inflammatory response. Furthermore, they presented data that a therapeutic inhibition of this reaction could stabilize the young patient and the existing excessive inflammatory reaction normalized.[4] For this publication in the renowned journal The Lancet Neurology, Dr. Lena-Luise Becker was awarded the Dr. Holger Müller Preis 2022.

“The award means an incredible amount to me in my still young career. (…) I am also very grateful for this recognition of my commitment to date, but I also see it as a mandate to continue to work intensively for children with rare diseases.”

Within the framework of a current international collaboration, further patients are to be genetically examined in order to find those affected who can be helped by the drug therapy described.

In cooperation with the Dr. Holger Müller Foundation, the Care-for-Rare Foundation has been offering the annual 5,000-euro Dr. Holger Müller Preis since 2011, which honors individual scientists or a group who have published a groundbreaking scientific contribution on rare diseases in the respective previous year. The aim is to encourage researchers to devote their research activities to urgently needed research into rare diseases.