NCT03855631: Epi-KAB

Exploiting Epigenome Editing in Kabuki Syndrome: a New Route Towards Gene Therapy for Rare Genetic Disorders

Completed Last updated 1 December 2020

What this trial tests

trial testing Intervention on primary cultured cells in Kabuki Syndrome 1 in 8 participants. Completed in 27 November 2020.

Timeline

28 September 2020

Primary endpoint
27 November 2020

27 November 2020

Quick facts

Lead sponsor	University Hospital, Montpellier
Status	Completed
Study type	OBSERVATIONAL
Enrollment	8
Start date	28 September 2020
Primary completion	27 November 2020
Estimated completion	27 November 2020
Sites	1 location across France

Drugs / interventions tested

• Intervention on primary cultured cells

Conditions studied

• Kabuki Syndrome 1 — all drugs for Kabuki Syndrome 1 →

Sponsor

University Hospital, Montpellier

Who can join

6 and older, any sex, with Kabuki Syndrome 1. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Starting from isolating primary cells from affected patients, an in vitro disease model system for KS will be developed. Using alternative strategies to obtain patient-derived mesenchymal stem cells, an integrative approach will be adopted for defining both the transcriptional and epigenetic regulatory networks perturbed upon the loss of function of KMT2D. Combining the self-renewal potential of mesenchymal stem cells (MSCs) with CRISPR/Cas9 technology, an epigenome editing approach as therapeutic strategy to rescue the activity of MLL4 will be developed.

A step forward is expected towards the understanding of those the molecular mechanisms governing the aetiology of Kabuki Syndrome (KS) and that the proposed in vitro disease model will provide to the scientific community an experimental system to study the KS. Importantly, the aim is to define the molecular bases of KS and to develop a therapeutic strategy that could ameliorate some of the abnormalities associated with KS.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Challenges and advances in clinical applications of mesenchymal stromal cells.
   Zhou T, Yuan Z, Weng J, Pei D, et al · · 2021 · cited 489× · PMID 33579329 · DOI 10.1186/s13045-021-01037-x
2. Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing.
   Zhang S, Shen J, Li D, Cheng Y. · · 2021 · cited 266× · PMID 33391496 · DOI 10.7150/thno.47007
3. A Brief Overview of Global Trends in MSC-Based Cell Therapy.
   Jovic D, Yu Y, Wang D, Wang K, et al · · 2022 · cited 186× · PMID 35344199 · DOI 10.1007/s12015-022-10369-1
4. Human Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Acquire Rejuvenation and Reduced Heterogeneity.
   Wruck W, Graffmann N, Spitzhorn LS, Adjaye J. · · 2021 · cited 48× · PMID 34604216 · DOI 10.3389/fcell.2021.717772
5. CRISPR/Cas systems: Delivery and application in gene therapy.
   Huang J, Zhou Y, Li J, Lu A, et al · · 2022 · cited 47× · PMID 36483767 · DOI 10.3389/fbioe.2022.942325
6. New frontiers to cure Alport syndrome: COL4A3 and COL4A5 gene editing in podocyte-lineage cells.
   Daga S, Donati F, Capitani K, Croci S, et al · · 2020 · cited 36× · PMID 31754267 · DOI 10.1038/s41431-019-0537-8
7. The comparison of ZFNs, TALENs, and SpCas9 by GUIDE-seq in HPV-targeted gene therapy.
   Cui Z, Liu H, Zhang H, Huang Z, et al · · 2021 · cited 33× · PMID 34938601 · DOI 10.1016/j.omtn.2021.08.008
8. The power and the promise of CRISPR/Cas9 genome editing for clinical application with gene therapy.
   Guo N, Liu JB, Li W, Ma YS, et al · · 2022 · cited 32× · PMID 36100322 · DOI 10.1016/j.jare.2021.11.018