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Rome, 17 January 2023 – An Italian multicentre study has identified some of the pathological mechanisms involved in cell malfunction in Smith-Magenis Syndrome (SMS), a rare and complex genetic disorder that affects child development.
The research was conducted at the IRCCS Fondazione Casa Sollievo della Sofferenza, by an all-Italian team, coordinated by Dr Jessica Rosati under the supervision of Prof. Angelo Vescovi, in collaboration with the research group of Prof. Maria Pennuto of the Veneto Institute of Molecular Medicine VIMM, the Fondazione Policlinico Universitario Agostino Gemelli IRCCS and the Istituto Neurologico Carlo Besta IRCCS, two of the most important clinical centers for the treatment of children affected by Smith-Magenis Syndrome.
The paper entitled: “Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome” was published in «Cell Death and Disease», scientific journal of the Nature Publishing group.
Smith-Magenis Syndrome (SMS) is a rare genetic disease, caused in 90% of cases by a deletion in the short arm of chromosome 17 (17p11.2) and, in the remaining 10%, by point mutations in the RAI1 gene. Children with this syndrome present mild-to-moderate intellectual disability, and strong long-term memory deficits, craniofacial dysmorphisms, obesity, sleep disturbance and behavioural symptoms. Worldwide prevalence is 1/15,000-25,000 in all ethnic groups, but it is a high probability that there is an underestimation in the diagnoses.
This research constitutes a milestone in the study of pathology because, until today, Smith-Magenis Syndrome has been predominantly studied from a clinical point of view. The project, started five years ago with the isolation of cells from a first patient, was subsequently extended to a significant number of patient-specific cell lines, with the cooperation of the Italian Smith Magenis Association. In vitro analysis has shown common pathological processes within all patients’ cells of the study, despite the tremendous genomic and symptomatological variability of each of them. Specifically, it has emerged how triglycerides accumulate in the cells of children affected by this syndrome due to a deregulation of the cellular waste disposal process, altering cell homeostasis and overwhelming the system, which in turn produces a high concentration of free radicals that provoke cell death.
«We were able to improve the pathological phenotype of cells acting specifically on the biochemical mechanism affected by the genetic mutation. This drug reduces both the accumulation of triglycerides and of free radicals, achieving an improvement in cell vitality » explained Angelo Vescovi, Scientific Director of IRCCS Casa Sollievo della Sofferenza and Project Coordinator.
The results of this study – and its important implications – identify, for the first time, the pathological processes occurring in the cells of patients with Smith-Magenis Syndrome (SMS), these deregulated processes will represent therapeutic targets for a future experimental therapy. Since 1986, when it was first diagnosed, no effective treatment has yet been developed. The next steps of the study involve a pre-clinical phase to be activated as soon as possible
Source: www.revertonlus.org
