Potential blood biomarker for SPG28 identified

Biochemical studies shed light on disease mechanism

A potential blood-based biomarker has emerged from a study of SPG28 mice. Mice blood samples were compared with samples from people with SPG28, identifying a class of compounds affected by the loss of function of the DDHD1 gene.


Hereditary spastic paraplegia is a genetic neurological disorder characterized by spasticity of the lower limbs, and spastic paraplegia type 28 is one of its subtypes.

Spastic paraplegia type 28 is a hereditary neurogenerative disorder with an autosomal recessive inheritance caused by loss of function of DDHD1. DDHD1 encodes phospholipase A1, which catalyzes phospholipids to lysophospholipids such as phosphatidic acids and phosphatidylinositols to lysophosphatidic acids and lysophoshatidylinositols.

Quantitative changes in these phospholipids can be key to the pathogenesis of SPG28, even at subclinical levels. By lipidome analysis using plasma from mice, we globally examined phospholipids to identify molecules showing significant quantitative changes in Ddhd1 knockout mice. We then examined reproducibility of the quantitative changes in human sera including SPG28 patients. We identified nine kinds of phosphatidylinositols that show significant increases in Ddhd1 knockout mice. Of these, four kinds of phosphatidylinositols replicated the highest level in the SPG28 patient serum. All four kinds of phosphatidylinositols contained oleic acid. This observation suggests that the amount of oleic acid-containing PI was affected by loss of function of DDHD1.

Our results also propose the possibility of using oleic acid-containing PI as a blood biomarker for SPG28.

SOURCE:  Biomedicines 2023, 11(4), 1092; https://doi.org/10.3390/biomedicines11041092

Oleic Acid-Containing Phosphatidylinositol is a Blood Biomarker Candidate for SPG28

Takuya Morikawa 1, Masatomo Takahashi 2, Yoshihiro Izumi 2, Takeshi Bamba 2, Kosei Moriyama 1,3, Gohsuke Hattori 4, Ryuta Fujioka 5, Shiroh Miura 6, Hiroki Shibata 1

1. Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

2. Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

3. Department of Nutritional Sciences, Nakamura Gakuen University, 5-7-1, Befu, Jonan-ku, Fukuoka 814-0198, Japan

4. Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka 830-0011, Japan

5. Department of Food and Nutrition, Beppu University Junior College, 82, Kitaishigaki, Oita 874-8501, Japan

6. Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, 454, Shitsukawa, Toon 791-0295, Japan

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