Decoding Motor Neurone Disease

British physicist Stephen Hawking and the 1930’s US baseball player Lou Gehrig had something in common: both were diagnosed with Amyotrophic lateral sclerosis (ALS) or Motor Neurone Disease, also named after the US sportsman.

The disease, which causes the death of neurons controlling the voluntary muscles and results in stiffness and twitching, is accompanied by a loss of control over speaking, swallowing and breathing. ALS is incurable and its cause is still largely unknown.

Which is why the race is on worldwide to discover the factors that cause ALS in the 90% of cases where inherited genes are not the key factor.

The disease, which affects people aged between 50 and 65 is prevalent in Brazil with an incidence of five cases for every 100,000 inhabitants. This is slightly higher than in Europe or the US. Stephen Hawking is a rare exception to the prevalent age-group. He was diagnosed with ALS in 1963, when he was 21. His doctors gave him two years to live. Hawking turned 75 in January.

Stephen Hawking,  world-famous ALS sufferer. Photo Hawking,

Stephen Hawking, world-famous ALS sufferer. Photo Hawking,

So a team of Brazilian clinicians and scientists at the university hospital at Campinas Medical School (FCM-UNICAMP) in São Paulo State, is assessing imaging, blood and genetic markers to assist in the early diagnosis of ALS. “About 90% of patients survive for three to five years following diagnosis,” said Marcondes Cavalcante França, Jr., Head of the Neuromuscular Disease Division at UNICAMP.

The most recent results of research from Marcondes’ team were published in NeuroImage: Clinical. The article focuses on the use of magnetic resonance imaging (MRI) and advanced techniques to evaluate MRI-based parameters as biomarkers of ALS.

The researchers analysed MRI images from 63 ALS patients treated at UNICAMP’s hospital, focusing on the thickness of the cerebral cortex, the volume of deep brain basal ganglia, and white matter. They also analysed the spinal cord, comparing images obtained at the time that ALS was diagnosed with others obtained eight months later in order to observe progression of the disease.

“We found a change in cortical thickness in the precentral region, which is the primary motor region,” Marcondes said. “We also observed alterations in deep-brain white-matter tracts and in the corpus callosum [the nerve fibre bundle that spans the longitudinal fissure, connecting the brain’s right and left hemispheres]. Lastly, we detected a progressive reduction of spinal cord volume.”

According to Marcondes, previous research had already pointed to alterations in the cerebral cortex, “but quantification of the degree of spinal cord atrophy is new. Prior studies focused on the brain or spinal cord, but practically none addressed both at the same time.”

“We then compared the different image parameters to see which were the most sensitive for detecting progression of the disease,” he continued. “We found that they were the spinal cord images. The conclusion is that we should analyse the spinal cord more carefully because it’s one of the most sensitive markers for long-term monitoring of ALS patients and hence useful for prognostic assessments.”

The average time between the appearance of the first symptoms and a confirmed diagnosis is currently about 14 months in Brazil and about 12 months in the United States, Europe and Japan.

ALS, which is incurable, is the third most common neurodegenerative disease after Alzheimer’s and Parkinson’s and the one whose causes we know least about. “We don’t understand its etiology or what factors trigger it,” Marcondes said. He added: “However, we do know that 5-10% of cases have underlying genetic causes, and some 15 genes that are associated with the development of ALS when they mutate have been identified.”

Marcondes and his team are looking for imaging, blood and genetic markers to assist in the early diagnosis of ALS. The study was conducted under the aegis of the Brazilian Institute of Neuroscience & Neurotechnology (BRAINN), one of the Research, Innovation & Diffusion Centers (RIDCs) funded by FAPESP, and also resulted from the PhD research of Milena de Albuquerque, supervised by Marcondes.

A second line of research into ALS at Campinas is reviewing blood samples from both healthy and diseased patients. Marcondes and his team are looking at the samples for genetic markers, with a view to early diagnosis of a disease that typically  takes a long time for doctors to identify. Ribonucleic acid (RNA) is a molecule that helps to control protein synthesis in cells. MicroRNA is a type of RNA that regulates gene expression. “The conclusion is that analysis of microRNAs 206 and 424 as biomarkers shows strong potential to accelerate ALS diagnosis and estimate each patient’s individual prognosis,” Marcondes said.

A study by the group, with results published in the Journal of the Neurological Sciences, focused on the search for microRNAs that could serve as ALS markers. This study was also supported by FAPESP.

You can read a full article on this topic by journalist Peter Moon by clicking here.

The article “Longitudinal evaluation of cerebral and spinal cord damage in amyotrophic lateral sclerosis” (doi:, by Milena de Albuquerque, Lucas Melo T. Branco, Thiago Junqueira R. Rezende, Helen Maia Tavares de Andrade, Anamarli Nucci and Marcondes Cavalcante França, Jr., and published in NeuroImage: Clinical, can be read at

The article “MicroRNAs 424 and 206 are potential prognostic markers in spinal onset amyotrophic lateral sclerosis” (, by Helen M.T. de Andrade, Milena de Albuquerque, Simoni H. Avansini, Cristiane de S. Rocha, Danyella B. Dogini, Anamarli Nucci, Benilton Carvalho, Iscia Lopes-Cendes and Marcondes C. França, Jr., and published in the Journal of the Neurological Sciences, can be retrieved from


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