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Abstract Details

Functional studies and therapeutic strategies for SLC20A2-associated primary brain calcification
General Neurology
P6 - Poster Session 6 (12:00 PM-1:00 PM)

The five causative genes: SLC20A2, PDGFB, PDGFRB, XPR1 and MYORG for IBGC have been discovered in the past several years. The variants of SLC20A2 is the most frequent in the patients with familial IBGC in Japan (40-50%).

Idiopathic basal ganglia calcification (IBGC), also known as Fahr’s disease or recently, prevailingly, as primary familial brain calcification (PFBC), is a rare neurodegenerative disease. IBGC is characterized by abnormal mineral deposits, mostly calcium, in brain regions, mainly the bilateral basal ganglia, in addition thalamus, cerebellum and others. There is no effective therapy now.

We made Chinese hamster ovary (CHO) cells expressing SLC20A2 variant proteins using the Flp-In system (Flp-In CHO cells). We also made patient-derived iPSCs and differentiated the iPSCs into the target cells, the endothelial cells (ECs). Inorganic phosphate (Pi) transport activity was measured with 32 P assays.

Although Pi transport activity was abolished in the cells with all examined SLC20A2 variants except one variant, activity was maintained at 27.8% of the reference level in cells with a certain variant. The variant was discovered by chance in healthy members of an IBGC family. All procedures were approved by the ethic committees.

We confirmed that SLC20A2 variants caused the loss of function of the Pi transport activity in both Flp-In CHO cells and disease-specific iPSCs. A partial reduced Pi transport function of Pit2 might not be sufficient to induce brain calcification of IBGC.

These results also show that the pathophysiology IBGC is based on the dyshomeostasis of Pi in the brain. High levels of Pi in the interstitial space (ISF), CSF and perivascular space of blood capillaries may cause the deposits of mainly calcium and other many kinds of minerals. Mineralization may be more suitable for this condition than calcification. The partial increase of PiT-2 activity may lead to improved clinical manifestation.

Isao Hozumi, MD, PhD (Gifu Pharmaceutical University)
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Yuichi Hayashi (Department of Neurology, Gifu University Grad) Yuichi Hayashi has nothing to disclose.
Takayoshi Shimohata, MD, FAAN (Department of Neurology, Gifu University) Dr. Shimohata has nothing to disclose.
Takashi Inuzuka, MD, FAAN (Gifu Municipal Hospital) No disclosure on file