{"id":2732,"date":"2024-04-19T13:36:28","date_gmt":"2024-04-19T13:36:28","guid":{"rendered":"https:\/\/horizon.peachpuff-wolverine-566518.hostingersite.com\/?p=2732"},"modified":"2024-04-19T13:36:28","modified_gmt":"2024-04-19T13:36:28","slug":"battle-against-fatal-neurodegenerative-disease-advances-on-two-fronts","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/horizon\/2732\/battle-against-fatal-neurodegenerative-disease-advances-on-two-fronts\/","title":{"rendered":"Battle against fatal neurodegenerative disease advances on two fronts"},"content":{"rendered":"

European researchers are pioneering a vaccine and treatment for amyotrophic lateral sclerosis.<\/p>\n

By<\/em><\/strong> \u00a0Andrew Dunne<\/p>\n

In 2005, an American triathlete named Jon Blais was diagnosed with an incurable neurodegenerative disease known as amyotrophic lateral sclerosis, or ALS<\/a>. He was 33 years old.<\/p>\n

Given no more than five years to live, Blais set about ticking off his final bucket-list challenge: the annual \u201cIronman World Championship\u201d in the US state of Hawaii. In October 2005, six months after his diagnosis, he became the only person with ALS ever to cross the finish line.<\/p>\n

German-Dutch duo<\/strong><\/p>\n

At the following year\u2019s event, Blais was wheelchair-bound. By the time of the 2007 contest, he was dead.<\/p>\n

\u2018It shows how ALS can hit anybody at any age,\u2019 said Professor Dieter Edbauer, a specialist in the cell biological mechanisms of neurodegeneration at the German Center for Neurodegenerative Diseases, or DZNE<\/a>. \u2018Current drugs can extend life only by a few months.\u2019<\/p>\n

Edbauer leads a research project that received EU funding to develop a vaccine against the most common genetic variant of ALS. Called\u00a0GA-VAX<\/a>, the project began in 2022 and is due to run into 2025.<\/p>\n

In addition to the DZNE, GA-VAX includes a Dutch vaccine development and manufacturing company named Intravacc.<\/p>\n

Based in a science park near Utrecht, Intravacc acts as a partner to organisations worldwide seeking to turn vaccine ideas into preventive and therapeutic breakthroughs.<\/p>\n

Fast killer<\/strong><\/p>\n

First identified in 1869, ALS is characterised by the progressive degeneration of nerve cells in the spinal cord and brain.<\/p>\n

It often begins with spasms, twitching or a weakness in an arm or leg before quickly affecting all muscles. Most commonly, ALS hits people aged between 40 and 70 and about two people per every 100 000 worldwide<\/a> are newly diagnosed with the disease annually.<\/p>\n

\u2018No one has ever been cured of ALS and life expectancy is typically just two to five years, which is far worse than most cancers,\u2019 said Edbauer.<\/p>\n

Eureka moment\u00a0<\/strong><\/p>\n

He began his research career as a medical student working on cancer vaccines and later focused on the biology of Alzheimer\u2019s and Fragile X Syndrome \u2013 a genetic condition that causes intellectual disability.<\/p>\n

Then, more than a decade ago, Edbauer turned his attention to ALS as a result of a Eureka moment tied to a discovery by scientists in the US of a rare gene mutation.<\/p>\n

In 2011, these researchers found a mutation in a gene called C9orf72 that acts as a trigger for a form of ALS now known as C9-ALS.<\/p>\n

The mutation occurs when a small part of the DNA for the C9orf72 gene is repeated hundreds of extra times. Edbauer discovered that this \u201crepeat expansion\u201d leads to the production of toxic proteins that contribute to neuron degeneration.<\/p>\n

\u2018It was a crazy idea really, but we knew that ALS patients had a unique pathology,\u2019 he said. \u2018My hypothesis was that the C9orf72 repeat expansion could be translated into aggregating proteins, although this region of the gene is normally not translated at all.\u2019<\/p>\n

Edbauer said that he and his colleagues made antibodies against these repeat proteins and were \u2018stunned\u2019 when labelling all the mysterious aggregates uniquely present in the brain and spinal cord of C9-ALS patients.<\/p>\n

He found that his antibodies could block toxicity of the repeat proteins in cell culture and realised his early work on cancer vaccines might be applicable to ALS.<\/p>\n

Vaccine hope<\/strong><\/p>\n

Fast-forward to today and, through\u00a0GA-VAX, Edbauer is developing a vaccine that would prompt the immune system to produce antibodies against the most abundant of the harmful repeat proteins, called poly-GA.<\/p>\n

The planned vaccine has the potential to slow or even prevent the progression of ALS in C9-ALS patients, who account for between 5% and 10% of all cases of the disease.<\/p>\n

Previous results from a prototype vaccine in mice have been promising, according to Edbauer.<\/p>\n

\u2018We have shown that the prototype vaccine reduces the aggregation of harmful proteins and inflammation in the brain, ultimately preserving neuron function,\u2019 he said.<\/p>\n

Working with Intravacc has helped Edbauer improve the prototype vaccine used in mice for eventual use in humans. Before then, several steps are still needed.<\/p>\n

These include tests to refine the vaccine formulation and dose. With safety and efficacy data, the team can apply to conduct clinical trials on patients genetically tested for C9-ALS.<\/p>\n

That could happen as soon as 2026, with an actual vaccine possible less than a decade later, according to Edbauer.<\/p>\n

\u2018Maybe within five to 10 years it will become a more manageable disease,\u2019 he said.<\/p>\n

Brain barrier<\/strong><\/p>\n

Farther north in Europe, a regenerative-drugs expert named Merja Voutilainen also has ALS in her sights.<\/p>\n

An associate professor of regenerative pharmacology at the University of Helsinki in Finland, Voutilainen led an EU-funded project that involved groundbreaking work into a treatment for the disease.<\/p>\n

The treatment involves proteins that can increase neuron survival, growth and repair and protect against toxins. These proteins are so-called neurotrophic factors.<\/p>\n

Voutilainen\u2019s project was called FutureTrophicFactors<\/a> and wrapped up in January 2024 after five years. It focused on a way to deliver proteins with neurotrophic-factor properties to the brain.<\/p>\n

Traditionally, these proteins are too big to cross the blood brain barrier \u2013 a protective filter in the brain that allows only certain substances to pass through. The barrier is basically the brain\u2019s natural defence against foreign invaders.<\/p>\n

As a result, for such proteins to be effective, they require the tricky task of being injected directly into the brain.<\/p>\n

\u2018Brain injections are not easy to perform and not many doctors can do them,\u2019 said Voutilainen.<\/p>\n

Protein pathway<\/strong><\/p>\n

In\u00a0FutureTrophicFactors, Voutilainen and colleagues discovered smaller versions of proteins with neurotrophic-factor properties.<\/p>\n

Her team showed that these versions, called \u201cfragments\u201d, are small enough to penetrate the blood brain barrier while retaining their effectiveness.<\/p>\n

\u2018These fragments can cross the blood brain barrier, which is a breakthrough meaning they can be injected under the skin, like insulin, then go straight to the brain and the spinal cord,\u2019 Voutilainen said. \u2018They can be used for the treatment of neurodegenerative diseases such as ALS and Parkinson\u2019s.\u2019<\/p>\n

Pre-clinical trials in mice have shown that this treatment works, protecting and restoring motor neurons.<\/p>\n

In the wake of FutureTrophicFactors, the research team is preparing further preclinical trials on transgenic mice and rats to collect more data.<\/p>\n

Clinical testing on ALS patients could start during the next five years and the actual treatment might become available in five to 10 years, according to Voutilainen.<\/p>\n

She regards earlier, easier treatment as key to increasing the survival of neurons for people with ALS.<\/p>\n

\u2018I really hope through this work we can both slow down the disease and, at least partially, cure it,\u2019 said Voutilainen. \u2018I\u2019m optimistic.\u2019<\/p>\n

Research in this article was funded by the EU\u2019s Horizon Programme including, in the case of GA-VAX, via the European Innovation Council (EIC) and in the case of FutureTrophicFactors via the European Research Council (ERC). The views of the interviewees don\u2019t necessarily reflect those of the European Commission. <\/em><\/p>\n

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