Gene Therapies for Monogenic Autism Spectrum Disorders

Novel genome editing and transient gene therapies have been developed the past ten years, resulting in the first in-human clinical trials for monogenic disorders. Syndromic autism spectrum disorders can be caused by mutations in a single gene. Given the monogenic aspect and severity of syndromic ASD, it is an ideal candidate for gene therapies. Here, we selected 11 monogenic ASD syndromes, validated by animal models, and reviewed current gene therapies for each syndrome. Given the wide variety and novelty of some forms of gene therapy, the best possible option must be decided based on the gene and mutation.

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Mutation analysis of the NRXN1 gene in autism spectrum disorders

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2016-0031 ◽

2016 ◽

Vol 19 (2) ◽

pp. 17-22 ◽

Cited By ~ 6

Author(s):

H Onay ◽

D Kacamak ◽

AN Kavasoglu ◽

B Akgun ◽

M Yalcinli ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Autism Spectrum Disorders ◽

Children And Adolescents ◽

Gene Mutations ◽

Autism Spectrum ◽

Syndromic Autism ◽

Spectrum Disorders ◽

Strong Candidate ◽

Reduced Penetrance

AbstractThe aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient. The S14L and L748I mutations have been described in the patients with autism before. Both of these mutations were inherited from their father. In this study, two of 30 (6.7%) autism spectrum disorder (ASD) patients carrying NRXN1 gene mutations were detected. It indicates that variants in the NRXN1 gene might confer a risk of developing nonsyndromic ASD. However, due to the reduced penetrance in the gene, the causal role of the NRXN1 gene mutations must be evaluated carefully in all cases.

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Proteomics and Metabolomics Approaches towards a Functional Insight onto AUTISM Spectrum Disorders: Phenotype Stratification and Biomarker Discovery

International Journal of Molecular Sciences ◽

10.3390/ijms21176274 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6274

Author(s):

Maria Vittoria Ristori ◽

Stefano Levi Mortera ◽

Valeria Marzano ◽

Silvia Guerrera ◽

Pamela Vernocchi ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Biomarker Discovery ◽

Chromosomal Abnormalities ◽

Single Gene ◽

Clinical Decision Support Systems ◽

Clinical Decision ◽

Autism Spectrum ◽

Added Value ◽

Diagnostic Tools ◽

Spectrum Disorders

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.

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Assessment and Treatment in Autism Spectrum Disorders: A Focus on Genetics and Psychiatry

Autism Research and Treatment ◽

10.1155/2012/242537 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Merlin G. Butler ◽

Erin L. Youngs ◽

Jennifer L. Roberts ◽

Jessica A. Hellings

Keyword(s):

Autism Spectrum Disorders ◽

Chromosomal Abnormalities ◽

Psychiatric Treatment ◽

Single Gene ◽

Challenging Behaviors ◽

Autism Spectrum ◽

Metabolic Disturbances ◽

Dna Deletions ◽

Assessment And Treatment ◽

Spectrum Disorders

Autism spectrum disorders (ASDs) are neurobehavioral disorders characterized by abnormalities in three behavioral domains including social interaction, impaired communication, and repetitive stereotypic behaviors. ASD affects approximately 1% of children and is on the rise with significant genetic mechanisms underlying these disorders. We review the current understanding of the role of genetic and metabolic factors contributing to ASD with the use of new genetic technology. Fifty percent is diagnosed with chromosomal abnormalities, small DNA deletions/duplications, single-gene conditions, or metabolic disturbances. Genetic evaluation is discussed along with psychiatric treatment and approaches for selection of medication to treat associated challenging behaviors or comorbidities seen in ASD. We emphasize the importance of prioritizing treatment based on target symptom clusters and in what order for individuals with ASD, as the treatment may vary from patient to patient.

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Faculty Opinions recommendation of Lessons learned from studying syndromic autism spectrum disorders.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726890122.793545845 ◽

2018 ◽

Author(s):

Genevieve Konopka

Keyword(s):

Autism Spectrum Disorders ◽

Autism Spectrum ◽

Lessons Learned ◽

Syndromic Autism ◽

Spectrum Disorders

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Providing Interventions for Young Children With Autism Spectrum Disorders

Journal of Early Intervention ◽

10.1177/1053815111429970 ◽

2011 ◽

Vol 33 (4) ◽

pp. 321-332 ◽

Cited By ~ 21

Author(s):

Phillip S. Strain ◽

Ilene S. Schwartz ◽

Erin E. Barton

Keyword(s):

Autism Spectrum Disorders ◽

Young Children ◽

Children With Autism ◽

Autism Spectrum ◽

Future Research ◽

The Past ◽

Children With Asd ◽

Comprehensive Service ◽

Spectrum Disorders ◽

The One

Over the past 25 years, we have learned a great deal about the diagnosis, treatment, and impact of autism spectrum disorders (ASD) on young children and their families. The authors describe several overarching themes that have emerged in the educational research on young children with ASD. The focus of their article is on education-based research because public education remains the one comprehensive service to which all children with ASD are entitled to free of charge. Four themes (i.e., inclusion, systematic and effective instruction, intensity, and social context) are described in terms of the major findings and impact on policy and practices. The authors conclude with a summary of implications for future research for the next 25 years.

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IMPROVING SOCIAL COMMUNICATION SKILLS IN AUTISM SPECTRUM DISORDERS USING PROGRAMMABLE TOY ROBOTS

SOCIETY INTEGRATION EDUCATION Proceedings of the International Scientific Conference ◽

10.17770/sie2021vol3.6149 ◽

2021 ◽

Vol 3 ◽

pp. 173-184

Author(s):

Gilberto Marzano ◽

Simone Zorzi ◽

Valeria Tambato

Keyword(s):

Autism Spectrum Disorders ◽

Social Communication ◽

Autism Spectrum ◽

Exploratory Research ◽

Rapid Progress ◽

The Past ◽

Social Communication Skills ◽

Autistic People ◽

The Social ◽

Spectrum Disorders

Autism spectrum disorders (ASD) are a group of lifelong disabilities that affect people’s ability to communicate and understand social cues. An individual with ASD has difficulties in recognizing body language, making eye contact, and understanding other people’s emotions. Rapid progress in technology offers increasing possibilities for innovation in treatment for individuals with ASD.In recent years, advances have enabled programmable toy robots (PTRs) to help individuals improve their social skills and communication abilities. Over the past decade, the use of PTRs with autistic children has received considerable attention, even though research on this topic is in its infancy.This article analyzes the recent progress in the use of PTRs in the ASD scope. It illustrates an exploratory research conducted on four adolescents with ASD aimed at defining an experiment to evaluate the effectiveness of PTRs in their social communication.The exploratory research results are encouraging, although they demonstrated the complexity in determining the feasibility and validity of robots in the social communication of autistic people.

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«Resource class» model for inclusion of children with ASD from the point of view of education management: risks and possibilities

Autism and Developmental Disorders ◽

10.17759/autdd.2016140306 ◽

2016 ◽

Vol 14 (3) ◽

pp. 55-62

Author(s):

O.G. Pogonina

Keyword(s):

Autism Spectrum Disorders ◽

Inclusive Education ◽

Children With Autism ◽

Autism Spectrum ◽

Point Of View ◽

Class Model ◽

Education Management ◽

The Past ◽

Spectrum Disorders ◽

Disor Ders

«Resource class», or «Resource zone», is a model of inclusive education for children with autism spectrum disorders that has proved its effectivity in integraing children to comprehensive school system for the past five years. A resource class is a place where the resources for inclusion of a child with autism of other mental disor¬ders into the school community are gathered. Here, the point of ‘resource class’ model is explained, described are the experience of introduction of resource zone technology, risks and problems appearing when creating a resource class in school. Member of the council of the Regional public organization to help children with autism spectrum disorders «Contact», educators, shares her experience in creating a resource class for autistic children with parents’ effort in «School № 2009» in Moscow.

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