Neurodegenerative disorders are often associated to lipid metabolic alterations and secondary inflammatory processes, which can contribute to the progression of the diseases. Lipid and steroid hormone pathways are altered, as an example, in X-linked Adrenoleukodystrophy (X-ALD), a demyelinating disorder characterized by the abnormal accumulation of very long chain fatty acids (VLCFA). A mixture of glyceryl trioleate and glyceryl trierucate (GTOE), well known as Lorenzo's Oil, is able to normalize lipid metabolic alterations in patients although not always the progression of the disease. Our objective was to introduce conjugated linoleic acid isomers (CLA) as therapeutic approach for X-ALD and for other neurodegenerative disorders. In a first study we tested a mixture of GTOE (40 g/day) with CLA (5 g/day) for 2 months, in female heterozygous X−ALD individuals, to determine whether CLA is detected in the liquor and exerts a synergistic effect with GTOE. Since secondary inflammatory processes are present in this pathology, we evaluated Somatosensory evoked potentials (SEPs), interleukins, and other standard biochemical and clinical parameters. After the treatment, CLA was detected in the liquor indicating the passage through the blood-brain barrier and the mixture decreased the VLCFA 26:0 and the ratio 26:0/22:0 in plasma. SEPs were improved after the treatment with the mixture, whereas with dietary GTOE were found unchanged. Inflammation is known to be a crucial factor for X-ALD pathogenesis and other disorders. This concerted action results in an improvement of the SEPs, which is a sign of neurological improvement. Clinical studies are ongoing for testing GTOE+CLA in twelve males ALD patients with different phenotypes. Similar results as for females carriers were obtained. Our results are opening the field for a novel promising therapeutic strategy for X-ALD and other neurodegenerative disorders where inflammation plays a central role.
Conjugated linoleic acid as dietary therapeutic strategy for the treatment of neurodegenerative disorders / A. P etroni, M. Cappa, C. Bizzarri, G. Carta, P. Gonnelli, S. Banni. ((Intervento presentato al 10. convegno Congress of the ISSFAL tenutosi a Vancouver nel 2012.
Conjugated linoleic acid as dietary therapeutic strategy for the treatment of neurodegenerative disorders
A.P. EtroniPrimo
;
2012
Abstract
Neurodegenerative disorders are often associated to lipid metabolic alterations and secondary inflammatory processes, which can contribute to the progression of the diseases. Lipid and steroid hormone pathways are altered, as an example, in X-linked Adrenoleukodystrophy (X-ALD), a demyelinating disorder characterized by the abnormal accumulation of very long chain fatty acids (VLCFA). A mixture of glyceryl trioleate and glyceryl trierucate (GTOE), well known as Lorenzo's Oil, is able to normalize lipid metabolic alterations in patients although not always the progression of the disease. Our objective was to introduce conjugated linoleic acid isomers (CLA) as therapeutic approach for X-ALD and for other neurodegenerative disorders. In a first study we tested a mixture of GTOE (40 g/day) with CLA (5 g/day) for 2 months, in female heterozygous X−ALD individuals, to determine whether CLA is detected in the liquor and exerts a synergistic effect with GTOE. Since secondary inflammatory processes are present in this pathology, we evaluated Somatosensory evoked potentials (SEPs), interleukins, and other standard biochemical and clinical parameters. After the treatment, CLA was detected in the liquor indicating the passage through the blood-brain barrier and the mixture decreased the VLCFA 26:0 and the ratio 26:0/22:0 in plasma. SEPs were improved after the treatment with the mixture, whereas with dietary GTOE were found unchanged. Inflammation is known to be a crucial factor for X-ALD pathogenesis and other disorders. This concerted action results in an improvement of the SEPs, which is a sign of neurological improvement. Clinical studies are ongoing for testing GTOE+CLA in twelve males ALD patients with different phenotypes. Similar results as for females carriers were obtained. Our results are opening the field for a novel promising therapeutic strategy for X-ALD and other neurodegenerative disorders where inflammation plays a central role.
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