PhD Scientific Days 2025

Poster Session III. - K: Theoretical and Translational Medicine

Studying the effect of cariprazine in induced neurons directly reprogrammed from fibroblasts of patients with Huntington’s disease

Előadó neve

Abbas Anna Anoir

Neptun code

CCOMF0

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

+36703232602

Előadó e-mail címe

abbas.anna@semmelweis.hu

Az előadás címe

Studying the effect of cariprazine in induced neurons directly reprogrammed from fibroblasts of patients with Huntington’s disease

Szerző(k) neve és munkahelye

Anna Anoir Abbas¹, Idris J. Jimoh², Anikó Göblös³, Roger A. Barker⁴, Zoltán L. Veréb³, Johan Jakobsson⁵, Lajos Kemény⁶, Tibor Pankotai⁶, Judit Mária Molnár², Karolina Pircs⁷

1: HCEMM, Semmelweis University
2: Semmelweis University
3: University of Szeged
4: University of Cambridge
5: Lund University
6: HCEMM, University of Szeged
7: HCEMM, Semmelweis University, Lund University

Bemutatás módja

Poszter

Szekció

Poster Session III. - K: Theoretical and Translational Medicine

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Huntington’s disease (HD) is an uncurable autosomal dominant progressive neurodegenerative disorder. The role of the dopaminergic system in developing HD symptoms is crucial, as the central dopaminergic pathways are overactivated in HD. Several drugs can reduce dopaminergic overactivity. However, their effectivity on psychiatric symptoms is limited. Moreover, the treatment of apathy and cognitive symptoms still remains challenging in HD. Cariprazine, a third-generation antipsychotic, is acting as a dopamine D3 and D2 receptor agonist. Previous results showed a positive effect in HD patients after cariprazine treatment. Clinical studies indicated positive effects in early-stage HD patients after cariprazine treatment in some psychiatric symptoms such as depressed mood, apathy and cognitive function in patients. Moreover, cariprazine also improved dopamine imbalance in the prefrontal cortex.
In this study, we investigate the effects of cariprazine using a novel in vitro model of HD, employing donor-derived aged induced neurons (iNs). Our objective is to elucidate the putative therapeutic effects of cariprazine and its mechanism of action, with a particular focus on autophagy. Using a reverse translational approach, we applied cariprazine treatment to iNs directly reprogrammed from fibroblasts of healthy controls, drug-naïve HD patients, and cariprazine-treated HD patients. High-content automated microscopy coupled with immunocytochemistry was employed for morphological and autophagy analyses. Our findings indicate that cariprazine treatment ameliorates the neurite abnormalities characteristic of HD-iNs. Furthermore, cariprazine modulated autophagic processes, suggesting a potential role in restoring subcellular autophagic dynamics. Notably, treatment with cariprazine led to a reduction in HTT gene expression. Comparative analyses with other D2/D3 antipsychotic agents suggest that these effects are attributed to the unique structural properties of cariprazine. This study provides compelling evidence supporting the therapeutic potential of cariprazine in HD.

University

Semmelweis University

Supervisor

Karolina Pircs

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7375

Start

14:12

End

14:18