Stem Cell Therapy May Be Protective in Cases of Huntington’s Disease

This paper examines methods to improve potential beneficial effects of stem cell therapy in Huntington’s disease.

ABSTRACT

Lercanidipine boosts the efficacy of mesenchymal stem cell therapy in 3-NP-induced Huntington’s disease model rats via modulation of the calcium/calcineurin/NFATc4 and Wnt/β-catenin signalling pathways.

Neurochem Int. 2019 Sep 17:104548. doi: 10.1016/j.neuint.2019.104548. [Epub ahead of print]

Elbaz EM1, Helmy HS1, El-Sahar AE2, Saad MA3, Sayed RH4.

Author information

Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; School of Pharmacy, Newgiza University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: [email protected].

Abstract

3-Nitropropionic acid (3-NP) induces a spectrum of Huntington’s disease (HD)-like neuropathologies in the rat striatum. The present study aimed to demonstrate the neuroprotective effect of lercanidipine (LER) in rats with 3-NP-induced neurotoxicity, address the possible additional protective effect of combined treatment with bone marrow-derived mesenchymal stem cells (BM-MSCs) and LER, and investigate the possible involvement of the Ca2+/calcineurin (CaN)/nuclear factor of activated T cells c4 (NFATc4) and Wnt/β-catenin signalling pathways. Rats were injected with 3-NP (10 mg/kg/day, i.p.) for two weeks and were divided into four subgroups; the first served as the control HD group, the second received a daily dose of LER (0.5 mg/kg, i.p.), the third received a single injection of BM-MSCs (1 x 106/rat, i.v.) and the last received a combination of both BM-MSCs and LER. The combined therapy improved motor and behaviour performance. Meanwhile, this treatment led to a marked reduction in striatal cytosolic Ca2+, CaN, tumour necrosis factor-alpha, and NFATc4 expression and the Bax/Bcl2 ratio. Combined therapy also increased striatal brain-derived neurotrophic factor, FOXP3, Wnt, and β-catenin protein expression. Furthermore, haematoxylin-eosin and Nissl staining revealed an amelioration of striatum tissue injury with the combined treatment. In conclusion, the current study provides evidence for a neuroprotective effect of LER and/or BM-MSCs in 3-NP-induced neurotoxicity in rats. Interestingly, combined LER/BM-MSC therapy was superior to cell therapy alone in inhibiting 3-NP-induced neurological insults via modulation of the Ca2+/CaN/NFATc4 and Wnt/β-catenin signalling pathways. LER/BM-MSC combined therapy may represent a feasible approach for improving the beneficial effects of stem cell therapy in HD.

PMID: 31539560

DOI: 10.1016/j.neuint.2019.104548