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22q11.2 Deletion Syndrome – 20 years of diagnostics and research in Serbia

STREAMLINE 2nd Symposium

On Saturday, September 9th, the second Symposium entitled “22q11.2 Deletion Syndrome – 20 years of diagnostics and research in Serbia” was organized within the STREAMLINE project. This event gathers around families of patients with 22q11.2 deletion syndrome, and also experts in this area, giving them a chance to discuss about latest advances related to this syndrome.

The day started with Dr. Goran Čuturilo and Dr. Danijela Drakulić talking about two decades of 22q11.2 Deletion Syndrome diagnostic and research in Serbia. The opening speech was followed by presentations from representatives of National organization for rare diseases of Serbia (NORBS) and “22q ex YU”, Milica Perić and Vesna Vujičić, who talked about the current activities of their associations. Afterwards, clinicians from the University Children’s Hospital Tirsova, assist. dr Igor Stefanović, dr Srđa Janković and psychologist Sara Bečanović, gave their scientific talks with some practical advices.

STREAMLINE team members spent this wonderful day with patients and their families, enjoying the nature, watching animals and riding horses. This was a great opportunity to better understand the life of patients with 22q11.2 deletion syndrome and their daily struggles, but also to become familiar with their way of thinking and their many talents. Perhaps the most important thing is that this Symposium enabled parents who share the same problems to exchange experiences, to broaden perspectives, and create new contacts.

At the end of the Symposium, the impressions of participants were very positive and some of the people who attended shared their experience on social media, documenting activities and the wonderful atmosphere of this Symposium within STREAMLINE project.

For me, meeting of the families with 22q11 microdeletion children has always been traumatic. But, here I am today smiling and happy! A unique opportunity to meet parents and children with this syndrom from all over Serbia and to finally meet doctors in person and discuss with them. No trauma 💪👊 Our children have grown up. The great parental odyssey and the experience of life as a soldier are behind us. We are ready to share our knowledge and experience with young people becoming parents and to make their everyday life as easy as possible! These children are the most beautiful flowers. Nothing less ❤️🌷 Well done Ančika. Well done Andrija. Long live the life!

Za mene je susret porodica dece 22q11 mikrodelecije uvek bio traumatičan. Evo me danas nasmejana i srećna! Jedinstvena prilika da se sretnemo iz cele Srbije i da otvoreno razgovaramo sa lekarima i da se konačno lično upoznamo. Traume bez 💪👊 Deca su nam porasla. Iza nas je velika roditeljska odiseja i ratno iskustvo. Spremni smo da svoja znanja i iskustva podelimo sa mladim roditeljima i da im olakšamo svakodnevicu koliko toliko! Ova su deca najlepši cvetići. Ništa manje ❤️🌷Bravo Ančika. Bravo Andrija. Živeo život!

Here you can find some shared posts:

We would like to take the opportunity to thank everyone for supporting our Symposium and STREAMLINE project thus far and we are looking forward to host another gathering soon.

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Currently in progress

After reprogramming of the somatic cells of patients with the familial form of 22q11.2 Deletion Syndrome into induced pluripotent stem cells (iPSCs), researchers of the STREAMLINE project are currently conducting the next phase of research – the differentiation of iPSCs into neurons and astrocytes. Neurons and astrocytes originating from patients with 22q11.2DS and healthy controls will be characterized and gene expression profiles will be analyzed by next-generation sequencing to discover sets of differentially expressed genes. These studies can contribute to the discovery of the pathophysiological mechanisms underlying this disease as well as the identification of new potential drugs in the future.

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22q11.2 Deletion Syndrome – 20 Years of Diagnostics and Research in Serbia

We would like to announce the symposium titled “22q11.2 Deletion Syndrome – 20 Years of Diagnostics and Research in Serbia” will take place on September 9, as a part of the STREAMLINE project. This symposium is a great opportunity to meet with patients and families and to discuss the latest achievements in the field of studying the 22q11.2 Deletion Syndrome and neurodevelopmental disorders.

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STREAMLINE at BelBi 2023

The Belgrade Bioinformatics Conference (BelBi2023) was held last week (June 19-23) in Belgrade, Serbia, as a hybrid event. Conference was organized by Institute of Molecular Genetics and Genetic Engineering, University of Belgrade and many other co-organizators. This five-day conference included keynote and invited talks by experts, oral and poster presentations, and workshops. There were three main topics: Biological Data (including bioinformatics databases and algorithms, omics data, spatial transcriptomics, etc), Biomedical Informatics (including genome privacy and security, translational medical informatics, etc) and Theoretical Approaches to Bioinformation Systems (TABIS) (including talks about Computational systems biology, Computational neuroscience, Biological population modelling and many others).
STREAMLINE project was also a part of BelBi2023, through organization of workshop “Bioinformatics approaches in research of neurodevelopmental disorders” that was held on June 23th from 10 to 11 am. The thematic workshop was dedicated to the latest bioinformatics approaches for studying neurodevelopmental disorders. Participants had opportunity to hear dr Danijela Drakulić presenting overview of STREAMLINE exploratory research project, followed by presentation by Sofia Notopoulou (CERTH, Greece): „Multi-omics analysis in a cellular model of Parkinson’s disease“ and presentation by Jamie Wood (Cardiff University):„Transcriptomics guided bioinformatics modelling: Dissecting neurodevelopmental disorders“.
Also, Dr Danijela Drakulić and dr Nataša Kovačević-Grujičić presented poster related to research: “Application of principal component analysis (PCA) and analytical hierarchy process (AHP) in analysis of articulatory characteristics of phonemes of children with 22q11.2 Deletion Syndrome“ during one of poster sessions.

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STREAMLINE thematic workshop “Bioinformatics approaches in research of neurodevelopmental disorders”

It is our great pleasure to announce STREAMLINE thematic workshop “Bioinformatics approaches in research of neurodevelopmental disorders” that will be held at the Metropol Palace Hotel, Belgrade, Serbia, on June 23th from 10 to 11 am. The thematic workshop will be dedicated to the latest bioinformatics approaches for studying neurodevelopmental disorders.

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The presentation of STREAMLINE research activities at 8th Congress of the Serbian Neuroscience Society

8th Congress of the Serbian Neuroscience Society (May 31st – June 2nd, 2023) was held in Belgrade, at the Belgrade Youth Center. The Congress was organised by Serbian Neuroscience Society and Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia. On that occasion, researchers in the area of neuroscience from Serbia and abroad gathered together. The participants had opportunity to present their recent work throughout oral and poster presentations. The Congress also offered networking opportunities and fostered debate among participants. After the first day of the Congress concetrated around opening ceremony and lecture, the second day’s topics were brain stimulation, phase separation in neuronal physiology and pathology and open-access data and resources in neuroscience research; brain metabolism and dietary interventions. The last day was focused on brain disorders and neuroimmunoendocrine interactions.
Our two PhD students, Jovana Kostić and Ivana Simeunović, presented their posters related to the research of 22q11.2 deletions and duplications, which takes place under the auspices of the STREAMLINE project. Jovana Kostić presented „Genomic and clinical findings in patients with 22q11.2 duplication syndrome“ on June 2nd. Among the submitted abstracts, Ivana Simeunović was chosen for the oral presentation of the scientific work „Analysis of cohort of patients with 22q11.2 deletion syndrome – a Single-center Experience from Serbia“.

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22q at the Zoo – Worldwide Awareness Day

On Sunday, May 21st, two of our researchers attended the “22q at the Zoo – Worldwide Awareness Day” in Subotica, at the Palić zoo. The event was organized by non-governmental and non-profit association “22q ex YU”, founded by parents of children with microdeletion 22q11.2 who live in the territory of the former Yugoslavia. The main initiator of the event at worldwide level was the International 22q11.2 Foundation. This worldwide event gathers around families and friends of patients with 22q11.2 syndrome, and also professionals in this area, giving them a chance to socialize and raise public awareness of 22q11.2 syndrome. Participants are recognizable by wearing official “22q at the Zoo” red T-shirts. This year, our two researchers spread awareness at the Subotica zoo by handing out 22q11.2 fact sheets and educating guests and zoo visitors about the syndrome and STREAMLINE goals and activities.

Our researchers spent the day with patients and their families, enjoying the nature, watching animals and visiting kids adventure park. They gained insight into the life of patients with 22q11.2 syndrome and their daily struggles, but also became familiar with their way of thinking and their many talents. They also met people from a nonprofit organization called ’’Zvuci srca’’, which helps the inclusion of disabled individuals into society. Our researchers also got contact information of volunteer patients who will donate their cells for reprograming to iPSCs and thus contribute the research of neurodevelopmental disorders.

On this occasion, participants were introduced to the importance of the STREAMLINE project, the research and application potential of the “iPSC-based” model system. This is supported by the fact that some of the patients present at the event, signed up to donate their somatic cells for reprogramming. To our delight a lot of the participants already knew a lot about our project, some even attended our symposium at the child clinic „Tiršova“ on the 9th of december, 2023.

Here You can find how 22qexyu association saw this event: https://22qexyu.weebly.com/aktivnosti.html

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Spring school: iPSCs as a tool for modelling disease and discovering molecular mechanisms of NDDs

The first STREAMLINE school dedicated to the latest research methodologies and approaches for studding neurodevelopmental disorders was held from 26th to 28th of April. This Spring School was organized by IMGGE and Cardiff University and gathered 21 PhD students from Serbia and Bosnia. During this three-days event the young researchers had an opportunity to learn, throughout lectures and hands on trainings, about cell reprograming strategies, iPSCs maintenance and characterization as well as about current methodologies for their neural differentiation towards functional neurons and glial cells. The attendees got guidelines, from the experts in the field, how to design and deliver patient-based iPSC studies and they became familiar with the latest advances regarding drug development and crucial steps from disease modelling to translational research.  The Spring School offered an excellent environment for fruitful discussions and new connections. The participants also got a chance, through group practice, to design their own patient-based iPSC study by implementing the knowledge they gained. We hope that this experience will be beneficial for their career and for further scientific discoveries.

dan svesti o autizmu

Poremećaji iz spektra autizma i tretmani matičnim ćelijama

Poremećaji iz spektra autizma (ASD) su heterogeni neurorazvojni poremećaji koje karakterišu manje i veće poteškoće u verbalnoj komunikaciji i socijalnim interakcijama, kao i ograničen, stereotipan, repetitivan repertoar ponašanja, interesovanja i aktivnosti.

Procenjuje se da u svetu jedno od sto dece ima autizam (1)

Osobe obolele od autizma često imaju i neko od pridruženih oboljenja uključujući: epilepsiju, depresiju, anksioznost, poremećaj pažnje sa hiperaktivnošću (ADHD) i intelektualnu ometenost.

Oboljenje se četiri puta češće dijagnostikuje kod dečaka nego kod devojčica i može se desi u svakoj porodici, bez obzira na rasnu, nacionalnu i etničku pripadnost, socijalni i ekonomski status (Center for Disease Control and Prevention).

Iako se već u ranom detinjstvu mogu ispoljiti neki  od simptoma ASD, vrlo često se dijagnoza postavlja dosta kasnije (Center for Disease Control and Prevention).

Pretpostavlja se da su uzročnici nastanka poremećaja iz spektra autizma brojni i uključuju genetičke, imunološke i sredinske faktore, te ASD spada u grupu multifaktorijalnih oboljenja. Blizanačke studije i studije porodica ukazuju na veliku naslednost u opsegu od 40-90%. Otkriveno je više od 1000 gena i mesta u genomu koji su povezani sa ASD (2). Pored naslednog opisani su i neki drugi faktori rizika za nastanak ASD, npr. izloženost majki u toku trudnoće hemikalijama (toluen, pesticidi) ili teškim metalima (živa, olovo, arsenat…), infekcije tokom trudnoće, perinatalna trauma, hipoksija, prevremeni porođaj…(2)

Terapije su najčešće usmerena na uklanjanje simptoma koji otežavaju svakodnevno funkcionisanje i umanjuju kvalitet života.  Deca sa autizmom odrastaju u osobe sa autizmom, kojima je potrebna podrška tokom celog života. Naučno je dokazano da se ranim prepoznavanjem, te ciljanom ranom intervencijom značajno može poboljšati životni ishod osoba s autizmom.

Tretmani matičnim ćelijama dece obolele od ASD daju ohrabrujuće rezultate. Tako je autologna transplantacija matičnih ćelija iz krvi pupčanika, sprovedena na dvadesetpetoro obolele decece uzrasta 2 do 5 godina, dovela do ublažavanja simptoma ADS u prvih 6 meseci nakon intravenozne administracije matičnih ćelija, a postignuti efekat se održao i 12 meseci nakon tretmana (3). Međutim, potrebno je naglasiti da ukupni klinički ishod, postignut terapijom matičnim ćelijama, ne može biti u potpunosti efikasan bez dodatne neurorehabilitacije koja uključuje bihejvioralnu i govornu terapiju, psihološku podršku…(2).

U Tabeli se nalazi kratak pregled kliničkih studija terapije ASD matičnim ćelijama sprovedenih poslednjih godina. Informacije preuzete iz (2).

Autori

Godina

Broj pacijenata

Uzrast

Izvor matičnih ćelija

Način administracije

Sun et al. [4]

2020.

12

4–9 godina

Alogene iz pupčane vrpce (mezenhimalne matične ćelije)

intravenozno

Dawson et al. [5]

2020.

180

2-7 godina

Autologne ili alogene iz krvi pupčanika

intravenozno

Riordan et al. [6]

2019.

20

6-15 godina

Alogene iz pupčane vrpce (mezenhimalne matične ćelije)

intravenozno

Chez et al. [7]

2018.

29

2-6 godina

Autologne iz krvi pupčanika

intravenozno

Dawson et al. [3]

2017.

25

2-5 godina

Autologne iz krvi pupčanika

intravenozno

Reference:

(1) Global prevalence of autism: A systematic review update. Zeidan J et al. Autism Research 2022 March.
(2) Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder—A Systematic Review, Justyna Paprocka et al. Brain Sci. 2021 Dec; 11(12): 1606.
(3) Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial: Autologous Umbilical Cord Blood in Autism Spectrum Disorder. Dawson G. eta al. Stem Cells Transl. Med. 2017;6:1332–1339. doi: 10.1002/sctm.16-0474.
(4) Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder. Sun J.M., et al. Stem Cells Transl. Med. 2020;9:1137–1146. doi: 10.1002/sctm.19-0434.
(5) A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder. Dawson G., et al., J. Pediatr. 2020;222:164–173.e5. doi: 10.1016/j.jpeds.2020.03.011.
(6) Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Autism Spectrum Disorder in Children: Safety Profile and Effect on Cytokine Levels. Riordan N.H., et al., Stem Cells Transl. Med. 2019;8:1008–1016.
(7) Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism. Chez M., et al., Stem Cells Transl. Med. 2018;7:333–341. doi: 10.1002/sctm.17-0042.

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Realizacija XV edicije manifestacije UniStem Day

Petnaesta edicija UniStem dana (Dana matične ćelije) održana je 10. marta 2023. Ovo je najveća međunarodna manifestacija posvećena popularizaciji matičnih ćelija, namenjena prvenstveno srednjoškolcima.

U realizaciji ovogodišnje manifestacije učestvovalo je 14 država, 87 univerzitetskih centara i preko 30 000 đaka širom sveta. 

UniStem Day u Beogradu održan je pod okriljem Univerziteta u Beogradu, u organizaciji Instituta za molekularnu genetiku i genetičko inženjerstvo, uz pomoć i podršku STREAMLINE projekta i Bio Save Fondacije. U manifestaciji je učestvovalo oko 150 učenika iz ukupno 18 srednjih škola i gimnazija.

Manifestaciju je zvanično otvorio prof. dr Ratko Ristić, prorektor za međunarodnu saradnju, Univerziteta u Beogradu. Tokom prepodnevnog dela programa, održanog u Svečanoj Sali Rektorata, Univerziteta u Beogradu, đaci su imali priliku da se, kroz naučnopopularna predavanja i kratkometražni dokumentarni film, upoznavanje sa značajem matičnih ćelia i revolucionarnim otkrićima koja pomeraju granice savremene medicine. Ovom prilikom, dr Danijela Drakulić, predstavila je STREAMLINE projekat kroz predavanje o indukovanim pluripotentnim matičnim ćelijama kao model sistemu za proučavanje neurorazvojnih poremećaja. Srednjoškolci su sa velikom pažnjom pratili predavanja i vrlo aktivno učestvovali u diskusiji. U toku programa organizovana je i kratka međuuniverzitetska veb-konferencija u toku koje je beogradska publika imala priliku da pozdravi učesnike manifestacije u organizaciji italijaskih univerziteta iz Breše i Kalabrije.

Deo đaka je imao priliku da učestvuje i u poslepodnevnom delu programa organizovanom u prostorijama Instituta za molekularnu genetiku i genetičko inženjerstvo. U okviru ovih aktivnosti, đaci su  imali priliku da se upoznaju sa Centrom za sekvenciranje genoma i bioinformatiku, takođe, srednjoškolcima je demonstriran rad sa ćelijskim kulturama i zebra ribicama kao model sistemima za istraživanja. Na kraju dana đaci su učestvovali i u kratkom kvizu na kojem su pokazali impresivno znanje usvojeno iz sadržaja prezentovanih u toku manifestacije.

Zahvaljujemo se svim učesnicima i najavljujemo XVI ediciju manifestacije UniStem Day za 22. mart 2024. godine!