Omic Profile in Autism Spectrum Disorder: From Cellular Level Towards Future Treatments
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Blood sample collection for ASD cells model production and Omic studies.
- Who it may be relevant to
- Registry conditions: Autism Spectrum Disorder. Basic parameters: 3 years — 15 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This is an interventional non pharmacological study in pediatric patientis affected by Autism Spectrum Disorder. It ams to create a collection of iPSCs and hiNSCs derived from deeply characterized ASD patients, to omics-characterize the cells, and to study the behavioral pattern of microglia-like cells in the onset of ASD.
Detailed description
ASD is a neurodevelopmental disorder affecting about 1 in 36 children and with a frequency increasing over time, thus delineating a significant social and public health problem that needs to be faced, as well as an important field of study and research.
This project starts from the idea that complex diseases such as ASD must be tackled with a multidisciplinary approach.
The investigators are collecting a large number of somatic cells from ASD patients who have been highly characterized and stratified in subgroups from a clinical, genetic, neurological and neuropsychological point and reprogramming these cells into induced pluripotent stem cells from which the cells of three embryonic germ layers originate.
Combining the expertise of the two Units, the project will have two short-term results:
1. a large collection of cell models from highly characterized ASD patients that can be shared with scientific community to speed up the understanding of the causes of the disease 2. the knowledge of pathological pathways of cells belonging to well characterized patients: omic analyses will be correlated to clinical/genetic data to understand if a specific subgroup has specific omic profile or the same profile is common to all ASD subgroups, if a specific clinical feature or genetic polymorphism is correlated with omic data.
Interventions
- Biological Blood sample collection for ASD cells model production and Omic studies
The blood sample collection performed in the study is for research purposes only and therefore not collected for clinical purposes. The patient cohort is extensively studied and well stratified, so cell models production and subsequent Omic analyses could be cross-referenced with detailed phenotype data.
Primary outcome measures
- Measurement of severity of ASD core symptoms with ADOS2 [Time frame: 1 year]
- Measurement of severity of ASD core symptoms with SRS 2 [Time frame: 1 year]
- Measurement of developmental abilities with Griffiths III scales [Time frame: 1 year]
- Measurement of cognitive abilities with Wechsler scales [Time frame: 1 year]
- Measurement of cognitive abilities with Leiter 3 scales [Time frame: 1 year]
- Quantification of emotional and behavioral problems with CBCL [Time frame: 1 year]
- Verification on iPSs of presence/absence of expression of stem cell genes and genes from the three embryonic layers [Time frame: 1 year]
- Percentage of hiNSCs differentiating into astrocytes, oligodendrocytes, and neurons [Time frame: 1 year]
- Measurement of length of neurite growth in hiNSCs [Time frame: 1 year]
- Measurement of concentration of distinct lipid molecular species in ASD derived cells and control derived cells in order to assess the differences in lipidomic profiles [Time frame: 1 year]
Eligibility criteria
Inclusion criteria
- Defined ASD diagnosis according to DSM-5 criteria
- Age 3-15 years
- Informed consent signed by the guardians/legal representatives.
Exclusion criteria
- Exclusion criteria for Group 1 will be: having a defined genetic diagnosis or an overall clinical presentation strongly suggestive for a syndromic condition. For this definition we will apply the criteria ASD associated with at least one of the following: >=3 facial anomalies, >=1 major/>=2 minor malformation (following EUROCAT classification), clinical issue affecting >=2 systems. Children showing such phenotypes but having no current genetic diagnosis could not be included in the study. Patients with a syndromic presentation and confirmed genetic diagnosis will be included in the Syndromic Group 2.
- No standardized test to establish diagnosis
- Parents refusing to complete the consent form
- Impossible blood sample collection.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
Italy · 1 center
- Foundation IRCCS Carlo Besta Neurological Institute — Milan
Publications
- Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, Reilly SK, Lin L, Fertuzinhos S, Miller JA, Murtha MT, Bichsel C, Niu W, Cotney J, Ercan-Sencicek AG, Gockley J, Gupta AR, Han W, He X, Hoffman EJ, Klei L, Lei J, Liu W, Liu L, Lu C, Xu X, Zhu Y, Mane SM, Lein ES, Wei L, Noonan JP, Roeder K, Devlin B, Sestan N, State MW. Coexpression networks implicate human midfetal deep cortical proj PMID 24267886
- Wen Z, Nguyen HN, Guo Z, Lalli MA, Wang X, Su Y, Kim NS, Yoon KJ, Shin J, Zhang C, Makri G, Nauen D, Yu H, Guzman E, Chiang CH, Yoritomo N, Kaibuchi K, Zou J, Christian KM, Cheng L, Ross CA, Margolis RL, Chen G, Kosik KS, Song H, Ming GL. Synaptic dysregulation in a human iPS cell model of mental disorders. Nature. 2014 Nov 20;515(7527):414-8. doi: 10.1038/nature13716. Epub 2014 Aug 17. PMID 25132547
- Waizbard-Bartov E, Fein D, Lord C, Amaral DG. Autism severity and its relationship to disability. Autism Res. 2023 Apr;16(4):685-696. doi: 10.1002/aur.2898. Epub 2023 Feb 14. PMID 36786314
- Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67-81. doi: 10.1002/ana.20315. PMID 15546155
- Turco EM, Giovenale AMG, Sireno L, Mazzoni M, Cammareri A, Marchioretti C, Goracci L, Di Veroli A, Marchesan E, D'Andrea D, Falconieri A, Torres B, Bernardini L, Magnifico MC, Paone A, Rinaldo S, Della Monica M, D'Arrigo S, Postorivo D, Nardone AM, Zampino G, Onesimo R, Leoni C, Caicci F, Raimondo D, Binda E, Trobiani L, De Jaco A, Tata AM, Ferrari D, Cutruzzola F, Mazzoccoli G, Ziviani E, Pennuto PMID 36411275
- Sellgren CM, Sheridan SD, Gracias J, Xuan D, Fu T, Perlis RH. Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors. Mol Psychiatry. 2017 Feb;22(2):170-177. doi: 10.1038/mp.2016.220. Epub 2016 Dec 13. PMID 27956744
- Ryan KJ, White CC, Patel K, Xu J, Olah M, Replogle JM, Frangieh M, Cimpean M, Winn P, McHenry A, Kaskow BJ, Chan G, Cuerdon N, Bennett DA, Boyd JD, Imitola J, Elyaman W, De Jager PL, Bradshaw EM. A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants. Sci Transl Med. 2017 Dec 20;9(421):eaai7635. doi: 10.1126/scitranslmed.aai7635. PMID 29263232
- Rosati J, Ferrari D, Altieri F, Tardivo S, Ricciolini C, Fusilli C, Zalfa C, Profico DC, Pinos F, Bernardini L, Torres B, Manni I, Piaggio G, Binda E, Copetti M, Lamorte G, Mazza T, Carella M, Gelati M, Valente EM, Simeone A, Vescovi AL. Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies. Cell Death Dis. 2018 Sep 17;9(10):937. doi: 10.1038/s41419-018-0990- PMID 30224709
Identifiers
NCT: NCT07427940 · PNRR-MCNT1-2023-12377520 · PNNR Funding