Amylopectinosis of the fatal epilepsy Lafora disease resists autophagic glycogen catabolism

Abstract

In this Correspondence, B. Minassian and colleagues report that GHF201, an autophagy activator shown to diminish abnormal glycogen aggregates in a mouse model of Adult Polyglucosan Body Disease, fails to reduce such accumulations in a mouse model of Lafora disease.

Figure 1. The autophagic activator GHF201 does not impact PBs in the Epm2a^-/- mouse model of LD.

(A) Representative images of PASD-stained hippocampus, cortex, cerebellum, and striatum of mice treated with vehicle control or GHF201. Scale bar: 100 µm. (B) Histochemical quantification of PBs in different brain regions. (C) Biochemical quantification of total and insoluble (PB) glycogen in brain, heart, and skeletal muscle. (D, E) Representative immunohistochemistry (IHC) images with signal quantification of anti-GFAP (D) and anti-Iba1 (E) in hippocampus showing no amelioration of astrogliosis or microgliosis, respectively. Scale bar: 200 µm. Data information: Quantification of (B–E) based on n = 9 WT vehicle-treated, n = 7 WT GHF201-treated, n = 11–12 LKO vehicle-treated, and n = 12 LKO GHF201-treated mice. Statistically significant differences (Mann-Whitney tests) were demonstrated between WT and LKO mice, but not between GHF201 and vehicle-treated LKO mice for (B–D). Significance levels are indicated as *P < 0.05; ****P < 0.0001. All error bars represent SE. Source data are available online for this figure.