Repair Inducing Cognition Enhancers (RICE)

Therapeutic research in neurodegeneration mainly focusses on molecular mechanisms and disease hallmarks, but improvement on the functional level is often neglected. Therefore, the “repair team” of the NIC&R group couples a cognitive readout to molecular interventions in treatment of CNS damage so that we can provide a translational interpretation towards first-in-man trials. We focus on neurodegenerative disorders such as multiple sclerosis and Alzheimer’s disease.

You can contact us for:

• Functional and molecular readouts in animal models of multiple sclerosis and Alzheimer’s disease
• Molecular and cellular setups in relation to oligodendrocyte differentiation
• In vitro and in vivo gene-editing tools to modulate (epi)genetic processes on the cellular level (e.g. CRISPR/Cas9, in vivo micro-electroporation)

Short Bio

This research is integrated within the NIC&R group and is related to the research of Niels Hellings and Bieke Broux.

Peer reviewed pubmed (ncbi) publications: 110

Hirsch index Web of Science: H=32 (Sum of citations: 2997)

Hirsch index Google scholar : H=40 (Sum of citations: 4397)

Hirsch index Scopus: H=32 (Sum of citations: 3177)

Key publications

1. Donders Z., Skorupska I.J., Willems E., Mussen F., Van Broeckhoven J., Carlier A. *, Schepers M.*, Vanmierlo T. *Beyond PDE4 Inhibition: A Comprehensive Review on Downstream cAMP Signaling in the Central Nervous System
   Biomed Pharmacother. 2024 Aug;177:117009.
   
   
2. Willems E., Schepers M., Piccart E., Wolfs E., Hellings N., Ait-Tihyaty M., Vanmierlo T. The Sphingosine-1-Phosphate Receptor 1 Modulator Ponesimod Repairs Cuprizone-induced Demyelination and Induces Oligodendrocyte Differentiation
   FASEB J 2024 Jan 31;38(2):e23413. 
   
   
   
3. Tiane A., Schepers M., Reijnders R.A., van Veggel L., Chenine S., Rombaut B., Dempster E., Verfaillie C., Wasner K., Grunewald A., Prickaerts J., Pishva E., Hellings N, van den Hove D.*, and Vanmierlo T.* From methylation to myelination: epigenomic and transcriptomic profiling of chronic inactive demyelinated multiple sclerosis lesions
   Acta Neuropathol. 2023 Aug;146(2):283-299.
   
   
   
4. Schepers M., Paes D., Tiane A., Rombaut B., Piccart E., van Veggel L., Gervois P, Wolfs E., Lambrichts I., Brullo C., Bruno O., Fedele E., Ricciarelli R., ffrench-Constant C., Bechler M.E., van Schaik P., Baron W., Lefevere E., Wasner K., Grünewald A., Verfaillie C., Baeten P., Broux B., Wieringa P., Hellings N., Prickaerts J.*, and Vanmierlo T. *Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin-damaging hallmarks of multiple sclerosis
   Brain Behav Immun. 2023 Mar;109:1-22.
   
   
   
5. Paes D., Schepers M., Rombaut B., van den Hove D., Vanmierlo T. , Prickaerts J.
   The molecular biology of PDE4 enzymes as pharmacological targets: An interplay of isoforms, conformational states, and inhibitors
   Pharmacol Rev. 2021 Jul;73(3):1016-1049.
   
   
   
6. Koulousakis P. ^*, Tiane A^*. Hellings N., Prickaerts J. van den Hove D. ^*, Vanmierlo T. ^* A perspective on causality assessment in epigenetic research on neurodegenerative disorders. Neural Regeneration Research 2023 (in press) (IF 6.06)
   
   
   
7. Tiane A., Schepers M., Riemens R., Rombaut B., Vandormael P., Somers V., Prickaerts J., Hellings N., van den Hove D. ^*, Vanmierlo T.^* DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation. Cell Mol Life Sci. 2021 Oct;78(19-20):6631-6644. (IF 9.18)
   
   
   
8. Rombaut B., Kessels S., Schepers M., Tiane A., Paes D., Solomina Y., Piccart E., van den Hove D., Brône B., Prickaerts J. and Vanmierlo T. PDE inhibition in distinct cell types to reclaim the balance of synaptic plasticity. Theranostics. 2021 Jan 1;11(5):2080-2097. (IF 11.60)
   
   
   
9. van Veggel L.^*, Spaas J.^*, Schepers M., Tiane A., van Horssen J., Wilson D.M.III, Moya P., Piccart E., Hellings , Eijnde B.O., Derave W., Schreiber R., Vanmierlo T. Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders. Cell Mol Life Sci. 2021 May;78(10):4615-4637 (IF 9.18)
   
   
   
10. Martens N.^*, Schepers M.^*, Zhan N., Leijten F., Voortman G., Tiane A., Rombaut B., Poisquet J., van de Sande N., Kerksiek A., Kuipers F., Jonker J., Liu H. , Lütjohann D. ^*, Mulder T. ^*,
    Vanmierlo T. ^* 24(S)-Saringosterol prevents cognitive decline in a mouse model for Alzheimer’s disease. Mar Drugs. 2021 Mar 27;19(4):190. (IF 6.09)

Patent applications

• 10/10/2019 publication PCT Patent Application with Application numbers EP18165843.6 PCT/EP2019/05495 WO 2019/193091 on “Selective PDE4D inhibitors against demyelinating diseases”
• 02/06/2021 “COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR USE IN NEURODEGENERATIVE DISORDERS” - EP21177320.5

• Oligodendrocyte differentiation
• Epigenetic editing (CRISPR-dCas)
• Pyrosequencing
• Functional and molecular readouts in animal models of multiple sclerosis and Alzheimer’s disease
• Molecular and cellular setups in relation to microglial functioning
• In vitro and in vivo gene-editing tools to modulate (epi)genetic processes on the cellular level
• (e.g. CRISPR/Cas9, in vivo micro-electroporation)
• In silico: Exon composition mapping and isoform expression profiling (using ExonArray data or qPCR).
• In vitro:Isoform-specific knockdown and characterization of neuronal differentiation.
• In vivo: Cognitive phenotyping of rodents in behavioural tests.