Sunday July 10, 2022 – Author:
ham
Researchers from Germany are working on a therapeutic vaccination against the nervous disease amyotrophic lateral sclerosis (ALS). Thanks to EU funding, the prototype can now be further developed – at best it will make it to the clinic in a few years.
Amyotrophe Lateralsklerose – kurz IF – is a shock diagnosis. The neurodegenerative disease leads to the most severe disabilities and is always fatal. The reason is that harmful proteins are deposited in the motor neurons of the brain and spinal cord and cause them to die off. About 5 to 10 percent of all ALS diseases are caused by a mutation in the so-called C9orf72 gene and are therefore the most common genetic ALS variant.
Vaccine targets most common gene mutation
Scientists from the German Center for Neurodegenerative Diseases (DZNE) now want to use this gene mutation as a target for a therapeutic vaccine. There is already a prototype. Thanks to funding from the European Union of 2.5 million euros, the vaccine can now be further developed. The aim of the project is to bring the vaccine candidate into clinical research. To this end, the DZNE is cooperating with Intravacc BV, a global contractor for the development and manufacture of preventive and therapeutic vaccines.
Much research still needed
“Before we can test this approach in people with ALS, we have to establish the production of our vaccine in clinical quality and prove the safety of our approach in further studies,” explains Prof. Dieter Edbauer, research group leader at the DZNE Munich site. “All in all, we hope that the results of this joint project, with the help of Intravacc, will advance the widespread use of vaccines in debilitating neurodegenerative diseases.”
Vaccination is supposed to sharpen the immune system
Edbauer’s research group discovered that mutations in the C9orf72 gene lead to the formation of toxic proteins – especially large, chain-like molecules called “poly-glycine-alanine” (poly-GA). In transgenic mice, they trigger a clinical picture similar to ALS, which ultimately leads to the death of nerve cells. The vaccine candidate aims to stimulate the immune system to produce antibodies against these harmful poly-GA molecules. Experiments on mice showed that administration of the vaccine reduced poly-GA aggregates and largely prevented motor deficits. To maintain adequate antibody levels, the vaccine must be administered regularly.
The first clinical trial could begin in 2025
“The goal of our current project is to develop the vaccine to the point where it can be tested on humans,” says Dr. Jan Groen, CEO of Intravacc. Clinical trials can therefore probably begin in 2025. “Our experience in the development of similar conjugate vaccines for infectious diseases will significantly accelerate the preclinical development and support the start of the first clinical ALS vaccine trial in humans,” says Groen confidently.
More than 2,500 cases of the C9orf72 variant of ALS have been recorded in the US and Europe. An estimated 9,000 mutation carriers who are currently asymptomatic but are at risk of developing the disease within 10 years could also benefit from the new approach.