EU Awards €2.5M for Potential Vaccine for ALS Tied to C9orf72 Gene

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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

The European Innovation Council EIC Transition Grant will be used to further develop the vaccine, and also to scale up its production. The funding also will allow for final toxicology studies needed to support a future request to test 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), who are partnering on the vaccine’s development.

“There is an unmet need for effective, disease-modifying therapies to treat ALS patients,” said Jan Groen, PhD, the CEO of Intravacc, a contract development and manufacturing company that works 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.

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A research team from the DZNE identified this vaccine-based approach.

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

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

Gearing up 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 greatly accelerate the preclinical development and support the start of the first ever in human ALS vaccine clinical trial,” Groen said.

Mutations in the C9orf72 gene 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 called familial when the disease affects more than one person in the same family.

Specifically, the mutation in this gene causes excessive repeats of six nucleotides — GGGGCC — in the C9orf72 gene. G stands for guanine and C for cytosine, two of the four building blocks of DNA.

In the U.S. and Europe alone, more than 2,500 C9orf72-associated ALS cases have been reported, according to the vaccine’s developers.

Moreover, excessive GGGGCC repeats in the C9orf72 gene also are 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 (DPR), that can form toxic clumps and contribute to neurodegeneration.

Further work showed that treatment with antibodies against poly-Glycine-Alanine (poly-GA), the most abundant DPR in C9orf72-associated disease, suppressed poly-GA aggregation and transmission between cells in patient-derived brain sections grown in the lab.

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

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

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

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

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

“All in all, we hope that with the help of Intravacc, results from this joint project will advance the broad application of vaccines in debilitating neurodegenerative diseases,” Edbauer said.