venerdì, Marzo 29, 2024

Prodotti per la casa e danno alle cellule della mielina: il pericolo invisibile che danneggia maggiormente i bambini

L'esposizione umana alle sostanze chimiche ambientali, soprattutto durante le...

Trigonellina: l’alcaloide che agisce come tale ma anche come precursore di coenzimi enzimatici anti-aging

La sarcopenia è il declino correlato all’età del muscolo...

A new drug for autism: unravel, unpack, unsilence.

It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism’s characteristic triad of symptoms. Autism has a strong genetic basis, although the genetics of autism are complex; this arises due to interactions among multiple genes, the environment, and epigenetic factors which do not change DNA sequencing but are heritable and influence gene expression. Many genes have been associated with autism through sequencing the genomes of affected individuals and their parents. Nevertheless, many candidate genes have been located, with only small effects attributable to any particular gene. Most loci individually explain less than 1% of cases of autism. Several lines of evidence point to synaptic dysfunction as a cause of autism. Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with cell adhesion. Mostly instead, involve proteins that regulated synapse structure, cell signaling and/or neuronal maturation.

In an article published in the journal Nature Neuroscience, investigators report how low doses of romidepsin – a drug approved in the United States for the treatment of lymphoma – restores gene expression and social deficits are reversed in a murine model of autism. The new study is thought to be the first to demonstrate that it may be possible to alleviate this primary ASD symptom by targeting a large number of genes associated with the disorder. In their study, three days of treatment with low-dose romidepsin reversed social deficits in mice with the deficient SHANK3 gene, which is a known risk factor for ASD. The inversion of social deficits lasted for 3 weeks. The loss of SHANK3 interrupts the NMDA receptor, which helps to regulate emotions and cognition. The interruption caused problems in communication between brain cells and led to social deficits related to ASD. Researchers have shown that romidepsin is able to reverse social deficits by restoring gene function through an epigenetic mechanism.

Epigenetic mechanisms are genetic processes capable of activating and deactivating genes and altering their expression without modifying their underlying DNA code. There are several ways in which epigenetic mechanisms can alter gene expression without changing their DNA. For example, they can silence genes by attaching chemical labels to their DNA. However, the main epigenetic mechanism at work in ASD is the one that remodels the chromatin structure. One of the important findings of the new study is that it may be possible to address a large number of ASD-related genes with just one drug. Romidepsin is a modifier of histones, which are proteins that help organize DNA in the nucleus. The drug dissolves densely packed chromatin: the result is to restore gene expression by making genes more accessible to their regulators. With the help of genome screening, the researchers found that romidepsin restores gene expression in most of the 200 and more genes, which have been “silenced” in the autistic mouse model used in the study.

It is not an immaterial result: if the cause of autism is a genetic defect, only a genetic remedy can correct it. Could rhomidepsin be the starting milestone to pave the way?

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Qi L et al. Nature Neurosci. 2018 Mar 12.

Zhu W et al. Am J Med Genet A. 2018 Feb 9.

Engineer CT et al. Autism Res. 2018 Jan;11(1):59-68. 

Koberstein JN et al. Sci Signal. 2018 Jan 16; 11(513).

Latest

Prodotti per la casa e danno alle cellule della mielina: il pericolo invisibile che danneggia maggiormente i bambini

L'esposizione umana alle sostanze chimiche ambientali, soprattutto durante le...

Synucleinopathy diagnosis is “under the skin”: biopsy as the next generation tool for early detection

Synucleinopathies are neurodegenerative illnesses that cause phosphorylated alpha-synuclein protein...

Newsletter

Don't miss

Prodotti per la casa e danno alle cellule della mielina: il pericolo invisibile che danneggia maggiormente i bambini

L'esposizione umana alle sostanze chimiche ambientali, soprattutto durante le...

Synucleinopathy diagnosis is “under the skin”: biopsy as the next generation tool for early detection

Synucleinopathies are neurodegenerative illnesses that cause phosphorylated alpha-synuclein protein...

Il ruolo delle vitamine liposolubili nelle sindromi neuropsichiatriche

Introduzione La salute mentale è una componente integrale ed essenziale...
Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

Vaccino per allergia da fieno: gli svedesi fanno passi da gigante

L'allergia è diventata una malattia comune e centinaia di milioni in tutto il mondo soffrono di rinite allergica o febbre da fieno, con disagio...

Perchè compaiono le occhiaie? Una breve rassegna legata allo stile di vita

Perché spuntano le occhiaie? Quel fastidioso contorno occhi considerato da tutti un inestetismo, le occhiaie, sono qualcosa di cui tutti vorrebbero sbarazzarsi con uno schiocco...

La sindrome di Elijah Patino: un mistero che ora ha un gene ed un nome

Elijah Patino è un bambino di sette anni felice e in buona salute ora, ma ci è voluto un po’ per arrivarci. Per gran...