Something’s changing in the fight against amyotrophic lateral sclerosis (ALS).

For years, this neurodegenerative disease has been synonymous with uncertainty, suffering and limited treatment options. But in recent times, scientific breakthroughs have been painting a different picture: for the first time, innovative therapies, specialised start-ups and initiatives are emerging that offer hopeful results which could truly transform the future of ALS.

This collective drive comes not only from large firms and pharmaceutical companies. It’s also taking shape in universities, hospitals and research centres around the world, where researchers, doctors and experts are working day after day with the same goal: to understand ALS and come closer to finding a cure.

On Global ALS Awareness Day, we give voice to some of the people who, from the CaixaResearch community, are carrying out research to make this change possible and who can all state the same message: “I’m also working to cure ALS“. 

Understanding and diagnosing ALS

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease. It affects the neurons responsible for voluntary muscle activity, essential for functions such as walking and talking, and it eventually leads to paralysis and death. It’s estimated that 2 out of every 100,000 people worldwide are affected by ALS. In Spain, although there’s no official register, between 4,000 and 4,500 people suffer from ALS and, every year, 700 people develop the first symptoms of the disease, according to the Spanish Neurological Society (SEN). For all of them, the average life expectancy after diagnosis is five years, a terrible psychological blow for the patient and those close to them.

“Being diagnosed with ALS is a life-changing shock that’s difficult to describe. It’s a catastrophe. It’s the sword of Damocles hanging over you. It’s a death warrant. And it’s difficult, first for the patient and then for those closest to them, to digest, with a minimum of rationality, what’s happening to you, because you think it’s not real, hence the frustration” explains María José Arregui in MediaHub, President of the Luzón Foundation, an organisation that works to raise awareness of this disease, improve the quality of life of patients and their families and promote research, and with which “la Caixa” Foundation collaborates.

María José Arregui, President of the Luzón Foundation

Anabel Sáez Mas, a “la Caixa” Foundation fellow and PhD student in the group led by CaixaResearch researcher Óscar Fernández-Capetillo at Spain’s National Cancer Research Centre (CNIO), knows this only too well. “Researching ALS is, for me, a personal and scientific challenge. My father was diagnosed while I was studying for my degree and, since then, I’ve wanted to help improve our understanding of this disease” explains Sáez Mas. “ALS is a puzzle with a large number of pieces. We often don’t know what causes it and there are many different mutations involved. This makes it a huge challenge that needs urgent answers”.

That’s why she forms part of the group led by Fernández-Capetillo, which is working to understand the molecular causes that initiate the death of motor neurons in ALS patients. “Understanding the problem is the first step in trying to find solutions. Our initial findings suggest that ALS-associated mutations lead to the accumulation of defective ribosomal proteins, a kind of ‘molecular junk’ that causes toxicity. This phenomenon is also observed during ageing” says the CaixaResearch researcher. “In this context, we are working to find ways to clear these ribosomal protein aggregates, in order to explore their potential as a new therapeutic approach for ALS”.

Anabel Sáez and Fernández-Capetillo

Like Fernández-Capetillo and Sáez Mas, CaixaResearch researcher Benedetta Bolognesi, from the Institute for Bioengineering of Catalonia (IBEC), is working to understand some of the causes of this disease. “We’re focusing on the SOD1 protein, which harbours more than 180 mutations associated with the disease” she explains. Her research forms part of a large-scale project with the University of Wollongong and the Royal Melbourne Hospital in Australia to map the impact of all genetic changes in SOD1 on the different mechanisms that cause ALS. “This will enable earlier and more accurate diagnosis and will also lay the groundwork for more targeted and effective treatments for all ALS patients”.

Benedetta Bolognesi

The search for biomarkers, biological molecules found in our bodies that can signal the presence of the disease, is one of the most important areas of action against ALS. Finding them may lead to the development of faster and less invasive diagnostic tests, which could improve the prognosis of the disease. “I think we’ve reached a watershed in terms of ALS research. We’ve managed to put the disease on the public and social agenda and make it attractive to researchers” says María José Arregui, President of the Luzón Foundation.

One of the projects along these lines, which forms part of the collaboration between “la Caixa” Foundation and the Luzón Foundation, is that of Maite Mendioroz and Ivonne Jericó, researchers at the Miguel Servet Foundation (Navarrabiomed). Her team is working on a diagnostic technique developed in the field of oncology that could be applied to ALS patients: liquid biopsy. “When cells degenerate and die, they release their contents, including DNA, into the bloodstream. These circulating DNA molecules contain biochemical information about their cells of origin, which in the case of ALS are the diseased neurons” explains Mendioroz. “What we’re doing is isolating and studying this DNA by means of a blood test, as a new source of biomarkers, to develop a non-invasive test to help diagnose these neurodegenerative diseases”.

Maite Mendioroz and Ivonne Jericó

The team of Estela Area, a CaixaResearch researcher at the Margarita Salas Centre for Biological Research (CIB-CSIC), is also working towards this goal, albeit with a different approach. “ALS presents a large number of cellular dysfunctions without any clear cause. Our work proposes that these alterations could have a common origin: a defect in the regulation of lipid levels that affects the function of cell membranes” she says. “Our goal is to perform a longitudinal analysis of the changes in the lipid profile of ALS patients and thereby find representative biomarkers of the disease which, in the future, could become new therapeutic targets for its treatment”.

Estela Area

Treating and curing ALS

The CaixaResearch network is also working to find possible treatments for the disease. The team led by Ana Martínez at the Margarita Salas Centre for Biological Research is focusing on discovering and developing drug candidates with innovative mechanisms of action. “We’re working to modulate TDP-43, a protein in the cell nucleus that has a multitude of functions in the formation of other proteins. When the disease occurs, TDP-43 leaves the nucleus and localises in the cytoplasm, where it forms toxic accumulations” says Martínez. “We’ve designed several families of compounds that reduce this toxicity and return TDP-43 to the nucleus”.

Ana Martínez

On the other hand, the group co-led by Torres and Manuel Portero, IRBLleida researcher and recipient of a CaixaImpulse grant, is developing a new treatment for ALS that could be applicable to 97% of patients. “In this project, carried out in collaboration with the University of Oxford, we’re working with a fragment of messenger RNA that corrects a key alteration in a gene that’s essential for autophagy, a cleaning mechanism, to take place” explains the project leader and CaixaResearch researcher. “The work combines preclinical validation, market analysis and the design of a first clinical trial, and its results could pave the way for a new therapy for this incurable disease”.

Manuel Portero

A common goal

Scientific interest in understanding and curing ALS has been growing steadily in recent years. And it’s no coincidence: the disease has stopped being an overlooked mystery and is now a priority in biomedical research. This is demonstrated by the work of the researchers in the CaixaResearch network and the commitment of initiatives such as the Luzón Foundation, which are helping to push this cause nearer the top of the scientific and social agenda.

Today, their voices remind us that, far from being a lost battle, ALS research is a collective race. A process in which every advance counts and in which researchers, associations and patients are key pieces in order to complete a puzzle that’s complex but not impossible to solve.