A synthetic small molecule appears to improve motor function, counteract the loss of motor neurons and reduce inflammation in the spinal cord. In other words, to slow the progression of SMA, spinal muscular atrophy. Caution is required because these results, although encouraging, have so far only been obtained in mice. The data are published in Proceedings of the National Academy of Sciences by a group from the University of Turin, according to which MR-409 (this is the name of the small synthetic molecule) could represent a potential drug, in combination with other therapies. The research was conducted by the Division of Endocrinology and Metabolic Diseases at the Department of Medical Sciences of the University of Turin and by the Neuroscience Institute Cavalieri Ottolenghi (NICO). Co-author is also the US endocrinologist Andrew Schally, Nobel Prize for Medicine in 1977 for his discoveries on the functioning of the protein hormones of the brain, and in whose laboratory in Miami MR-409 is synthesized.
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La Sma
At the origin of this rare neuromuscular disease of childhood – which has an incidence of about 1 in 10,000 live births and manifests itself in various forms (SMA types 1, 2 and 3) – there is the loss of motor neurons, i.e. nerve cells that carry signals from the central nervous system to muscles, controlling their movement. This causes weakness and progressive muscle atrophy, especially in the lower limbs and respiratory muscles: symptoms caused by mutations affecting the SMN1 gene which compromise the correct functioning of the SMN (Survival Motor Neuron) protein, which is essential for motor neuron survival. Until recently, treatment was exclusively symptomatic and aimed at improving the quality of life of patients. Today, however, there are drugs that can increase the production of the functional protein and improve patient survival, but they do not represent a definitive cure.
Type 1 Sma, a drug improves long-term motor functions in children
by Dario Rubino
The effects of MR-409
So why would MR-409 be so promising? Because it is one of the analogous molecules of GHRH (growth hormone-releasing hormone), i.e. the neurohormone that stimulates the release of growth hormone and is able to carry out a protective action on muscle cells. This characteristic prompted the Turin researchers – who together with Nobel Schally had previously demonstrated the protective effects of GHRH analogues on the heart and muscles – to test it also in an experimental model of SMA. And in fact, its administration has proved capable of positively affecting the symptoms related to the deficiency of the SMN protein, improving motor functions, reducing muscle atrophy and promoting the maturation of the neuromuscular junctions, report the authors. But we will still have to wait some time before this class of molecules – known as GHRH agonists – will be available for human use: further studies are currently underway to obtain the authorization of these substances for clinical use.