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Novel in vitro approaches to study X-linked adrenoleukodystrophy

C Pérez-García(1,2) M L Molina(1) C Bueno(1) E Geijo-Barrientos(1) S Martínez(1)

1:Instituto de Neurociencias - UMH; 2:Universidad Católica de Murcia- UCAM

X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder caused by mutations in ABCD1 gene, causing the absence or dysfunction of ALDP, a peroxisomal transmembrane protein responsible of transportation of very long-chain fatty acids (VLCFA) from cytosol into peroxisome. Consequently, there is an accumulation of VLCFA in plasma and tissues. The clinical spectrum of X-ALD patients is wide variable, ranging from several phenotypes without correlation with genotype. The most devastating phenotype is characterized by an aggressive inflammatory demyelination. Unfortunately, there is not an effective therapy for all affected patients, highlighting the need for research.


A therapeutical option could be the use of bone marrow derived-mesenchymal stem cells (BMSCs). BMSCs have been proposed as a therapeutical approach in many neurological diseases as they have beneficial effect both in direct (cell-to cell contact) and indirect (paracrine signaling) mechanisms.


Here, we are developing a novel in vitro model to study X-ALD from dental pulp stem cells (DPSCs). We could analyse that DPSCs from a X-ALD patient showed specific phenotypical differences in comparison to healthy DPSCs. Also, X-ALD DPSCs could be differentiated into neural-like cells. Immunocytochemistry experiments revealed that X-ALD neural-like cells showed specific mature neural markers expression. Electrophysiological assays were carried out to further characterize X-ALD neural-like cells. These cells exhibited significant differences in amplitude and kinetics of sodium and potassium currents. Interestingly, when X-ALD neural-like cells were directly co-cultured with BMSCs, they rescued a healthy phenotype. Further investigation of the effect of BMSCs on X-ALD cells may provide relevant insights into X-ALD research.

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