A new €2.5 million (approximately $2.5 million) grant from the European Union (EU) will help advance a prototype vaccine against amyotrophic lateral sclerosis (ALS) associated with mutations in the C9orf72 gene – its most common genetic cause.

The EIC Transition Grant from the European Innovation Council will be used to further develop the vaccine, as well as to scale up its production. The funding will also allow for the final toxicology studies needed to support future application for testing the therapy in clinical trials, according to a press release announcing the grant.

It was awarded to Intravacc and the German Center for Neurogenerative Diseases (DZNE), which are partnering for the development of the vaccine.

“There is an unmet need for effective, disease-modifying therapies to treat patients with ALS,” said Jan Groen, PhD, CEO of Intravacc, a contract development and manufacturing company working to produce preventive and therapeutic vaccines.

“The goal of our current project is to develop the vaccine to the point where it can be tested in humans,” Groen said.

A DZNE research team identified this vaccine approach.

“We are grateful that the EU is supporting this development with the EIC Transition Grant,” said Dieter Edbauer, MD, the leader of this DZNE research team.

“Before we can test this approach in ALS patients, we need to establish clinical-grade production of our vaccine and conduct further safety studies,” said Edbauer, also associate professor at Ludwig Maximilian University of Munich. .

Preparing for clinical trials

According to Groen, clinical trials are now expected to begin in 2025.

“Our experience in developing similar conjugate vaccines for infectious diseases will significantly accelerate preclinical development and support the start of the first-ever ALS vaccine clinical trial in humans,” Groen said.

Mutations in the C9orf72 are the most common genetic cause of ALS, accounting for up to 50% of familial ALS cases and up to 10% of sporadic cases. ALS is said to be familial when the disease affects more than one person in the same family.

More specifically, the mutation of this gene causes excessive repetitions of six nucleotides – GGGGCC – in the C9orf72 embarrassed. G stands for guanine and C for cytosine, two of the four building blocks of DNA.

In the United States and Europe alone, more than 2,500 C9orf72– cases of associated ALS have been reported, according to the vaccine developers.

Moreover, excessive repetitions of GGGGCC in the C9orf72 are also one of the most common causes of frontotemporal dementia (FTD), a related condition.

About a decade ago, Edbauer’s research group discovered that these extra repeats lead to the production of abnormal proteins, called dipeptide repeat proteins (DPRs), which can form toxic clumps and contribute to neurodegeneration.

Other work has shown that treatment with antibodies directed against poly-glycine-alanine (poly-GA), the most abundant DPR in C9orf72-associated disease, suppression of poly-GA aggregation and cell-to-cell transmission in laboratory cultured patient-derived brain sections.

Based on these findings, the researchers hypothesized that using a vaccine to induce the body’s immune system to produce such antibodies could be a potential therapy for ALS and FTD related to C9orf72 genetic mutations.

In a mouse model of poly-GA-associated disease, the team found that this approach, when given before the onset of symptoms, effectively reduced the level of poly-GA aggregates and largely prevented neuroinflammation, neurodegeneration and motor deficits.

This approach will require regular vaccination to maintain sufficient antibody levels, the scientists noted.

Intravacc and DZNE estimate that in addition to C9orf72-ALS patients, approximately 9,000 people who carry the C9orf72 mutation and are at risk of developing symptoms within 10 years, could also benefit from this vaccine.

This vaccine or similar experimental vaccines may also help people with or at risk of developing FTD.

“Overall, we hope that with the help of Intravacc, the results of this joint project will advance the large-scale application of vaccines in debilitating neurodegenerative diseases,” Edbauer said.