Motor Neuron Disease Linked To Schizophrenia, And Treatment Might Be Getting Closer

An experimental treatment for motor neuron disease changed the concentration of a biomarker (brown areas) for the disease. T.F Gendron et al./Science Translational Medicine

Three announcements in a single week from separate research teams report progress against motor neuron disease (MND). These take us closer to being able to understand, detect, and treat this awful condition. Those ice buckets may have really made a difference.

For people with MND (also known as amyotrophic lateral sclerosis), the week's most exciting news is probably publication in the British Journal of Pharmacology that the anti-inflammatory drug PMX205 slows the progress of the inherited form of the disease in rats and mice. “In animal models, PMX205 made a visible difference to tremors, muscle strength and mobility, and if this is reflected in people, it could make a real difference to patients.” Dr John Lee of the University of Queensland said in a statement

Since around 90 percent of people with MND have what is known as the “sporadic” version, success against inherited MND is not such big news, but Lee and his colleagues think the chances are high that the majority of MND patients will also benefit. “At the moment, the only drug available for patients prolongs survival by two to three months at most,” Lee said. He hopes PMX205 can do better.

It takes a long time for drugs to get from the laboratory to the marketplace, but PMX205 has the advantage of already being used for other anti-inflammatory purposes, so some of the safety testing is already done. Lee's team are collaborating with a private company to undertake pre-clinical safety trials, which will run in parallel with efforts to confirm their suspicion of its relevance for sporadic MND. If both go to plan, clinical trials will start in 2019.

PMX205 is unlikely to prove a magic bullet, however, which makes the discovery of a genetic marker for the most common form of MND important. In Science Translational Medicine, the Mayo Clinic's Dr Tania Gendron has announced that people with the mutations most commonly associated with MND accumulate a protein known as polyGP in their cerebrospinal fluid and blood cells.

Whether or not polyGP proves a useful target in stopping the progress of the disease, Gendron hopes it can serve as a way of measuring the effectiveness of treatments, speeding up the search for effective drugs. It may also provide advanced warning of MND before symptoms begin.

The most amazing discovery, however, and perhaps ultimately the most important, is that there is a genetic overlap between MND and schizophrenia, despite the lack of resemblance between the diseases. In Nature Communications, a team led by Professor Orla Hardiman of Trinity College Dublin report on a comparison of the genetics of 13,000 people with MND and 30,000 with schizophrenia. Although schizophrenia risk scores accounted for just 0.12 percent of MND variation, the fact that this is not zero indicates common ground between the diseases that could guide research.

“We should think about ALS/MND in the same way that we think about schizophrenia, which is a problem of disruptions in connectivity between different regions of the brain, and we should look for drugs that help to stabilize the failing brain networks,” Hardiman said in a statement

The work follows the recent discovery that there is a negative correlation between the genetics of those with schizophrenia and people with rheumatoid arthritis, suggesting body-mind connections we have barely begun to understand.

Trinity scientists discover shared genetic origin for ALS/MND and schizophrenia from Infocus Media on Vimeo.

 

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