Research Roundup: a Potential Vaccine for ALS & More


Although many think of vaccines as preventions for infectious diseases, such as COVID-19, influenza and measles, researchers and biotech companies are working on developing vaccines against all sorts of illnesses, including cancer, and in this week’s lead story, amyotrophic lateral sclerosis (ALS). For that and more, continue reading. 

A Vaccine Against ALS?

DZNE and Intravacc were recently awarded €2.5 million from the European Union (EIC Transition Grant) to continue developing a prototype vaccine against amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease caused by the aggregation of specific abnormal genes in the brain and spinal cord motor neurons. It leads to paralysis and eventually death.

Approximately 5-to-10% of ALS cases are caused by a mutation in the C9orf72 gene. These patients have a massively expanded repeat region in a part of the gene that is otherwise silent. These repeat sequences code for a toxic protein, primarily large, chain-like poly-Glycine-Alanine (poly-GA), which triggers downstream pathology in mouse models, causing neurons to die.

DZNE produced an experimental vaccine that teaches the immune system to develop antibodies against these toxic poly-GA molecules. In a mouse model, the vaccine decreased poly-GA aggregates and mostly prevented motor deficits. To maintain sufficient antibody levels, regular vaccination was required. More than 2,500 prevalent C9orf72 ALS cases in humans have been identified in the U.S. and Europe, and about 9,000 mutation carriers with no symptoms are at risk of developing the disease within 10 years.

“There is an unmet need for effective, disease-modifying therapies to treat ALS patients,” Jan Groen, Ph.D., Intravacc’s chief executive officer said. “The goal of our current project is to develop the vaccine to the point where it can be tested in humans. Clinical trials for C9orf72 ALS, which is the most common genetic variant of ALS, are expected to commence 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.”

Nanoparticle Vaccine Protects Broad Spectrum of COVID-19 Variants 

Investigators at the California Institute of Technology developed a new type of vaccine that offers protection against a variety of SARS-like betacoronaviruses, including SARS-CoV-2 variants. The tests have been conducted on mice and monkeys.

These vaccines present the immune system with pieces of the spike proteins from SARS-CoV-2, the virus that causes COVID-19, and seven other SARS-like betacoronaviruses. They are attached to a protein nanoparticle structure. They also found that the animals receiving this mosaic nanoparticle vaccine had protection from the original SARS (SARS-CoV) virus, which was not one of the eight on the vaccine. They intend to launch a Phase I study of the vaccine in humans.

Possible New Treatment Approach for Psoriasis

Researchers at the Medical University of Vienna found that they could decrease the severity of psoriasis and psoriatic arthritis by inhibiting the S100A9 gene throughout the entire body instead of just locally on the skin. They found that the inflammatory responses in psoriasis and psoriatic arthritis were when S100A9 was only inhibited in skin cells.

When administered systemically via tablets or drips, they were found to be much more effective. In short, when the S100A9 I is inactivated in all cells of the body, psoriasis symptoms disappear. The study was published in the Annals of the Rheumatic Diseases.

“Our study is an important step towards the development of targeted therapeutic options in the form of drugs that act systemically rather than locally on the skin,” Erwin Wagner, Ph.D., who led the research said.

Rhythmic Small Intestinal Microbiome Prevents Obesity and Type 2 Diabetes

A microbiome refers to the trillions of microorganisms that live in and on the body. There are about 500 to 1,000 different bacterial species that live in each person’s gut. Researchers at the University of California San Diego School of Medicine explored in mice models how diet and feeding patterns affect the gut microbiome and the health of the hosts, with a particular focus on obesity and type 2 diabetes.

They point out that the gut microbiome constantly changes based on what we eat and on the time of day. By following the microbiomes over time rather than at specific points in time, they found that cyclical changes in the gut microbiome play an important role in health because they help the circadian clock, which regulates and controls glucose, cholesterol and fatty acids, as well as overall metabolic health.

Plant-Based Protein-Microbe Domain Linked to Human Cancer Triggers

Researchers with the Department of Energy’s Oak Ridge National Laboratory found that the plasminogen-apple-nematode (PAN) domain is tied to cell proliferation that drives tumor growth in humans. It also drives defense signaling during plant-microbe interactions in bioenergy crops. They identified four core amino acids called cysteine residues in the HGF protein that is critical to the PAN domain’s activities and looked at how they behaved in human cancer cell lines. Mutating any of the amino acids turned off the signaling pathway called HGF-cMET that is abnormally increased in cancer cells, making them multiply quickly and metastasize. They believe that this finding will open opportunities for new approaches to treating cancers, such as those that originate in the breast and stomach.

Watching Gene Expression in Live Mice Brains in Real-Time

University of Minnesota Twin Cities researchers developed a new imaging technique that allowed them to visualize messenger RNA (mRNA) molecules in the brains of living mice. The research, among many things, provided new insights into how memories are formed and stored. mRNA is produced during the process of forming and storing memories.

The process involved genetic engineering, two-photon excitation microscopy, and optimized image processing software. They genetically modified a mouse so that it generated mRNA labeled with green fluorescent proteins. This allowed them to see where and when the brain created Arc mRNA, the specific form of RNA they were studying. And because the mouse is alive, they could study it for longer periods.

They were able to image in real-time over a month what neurons were doing as the mouse formed and stored memories. They found a small group of cells that overlapped, consistently generating the Arc mRNA each day. It is in the retrosplenial cortex region of the brain, which is believed to be responsible for long-term memory storage.

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