RO0711401 / Roche - LARVOL DELTA

Impedance-based phenotypic profiling of metabotropic glutamate receptor ligand responses in SCA1 human iPSC-derived neuronal cultures. (PubMed, Neurobiol Dis) - "To specifically characterize mGluR1 function, mGluR1-specific positive- and negative allosteric modulators (Ro0711401 and JNJ16259685 respectively) were tested. Results showed reduced mGluR1 and decreased mGluR5 RNA expression levels and diminished mGluR1/5 responses in the SCA1 hiPS cell-derived neuronal cultures. These results underline the potential utility of impedance measurements for characterizing GPCR function and pharmacological testing in a high-throughput manner in patient-derived neuronal cultures."

Journal • Ataxia • CNS Disorders • Movement Disorders • GRM1

Targeting mGlu1 Receptors in the Treatment of Motor and Cognitive Dysfunctions in Mice Modeling Type 1 Spinocerebellar Ataxia. (PubMed, Cells) - "Using mice modeling SCA1, it has been demonstrated that a drug that amplifies mGlu1 receptor activation (mGlu1 receptor PAM, Ro0711401) improves motor coordination without the development of tolerance when cerebellar dysfunction manifests (i.e., in 30-week-old heterozygous ataxin-1 [154Q/2Q] transgenic mice)...This treatment also enhanced hippocampal levels of the endocannabinoid, anandamide, without changing the levels of 2-arachidonylglycerol. These findings suggest that mGlu1 receptor PAMs may be beneficial in the treatment of motor and nonmotor signs associated with SCA1 and encourage further studies in animal models of SCA1 and other types of SCAs."

Journal • Preclinical • Ataxia • CNS Disorders • Cognitive Disorders • Movement Disorders

Modulation of thalamic and cortical GABA transporter: the potential mechanism for the anti-absence activity of mGlu5 receptors. (Neuroscience 2016) - "It has been demonstrated that acute treatment with positive allosteric modulators (PAMs) of mGlu1 and mGlu5 metabotropic glutamate receptors (RO0711401 and VU0360172, respectively) dose dependently reduces the incidence of spike-and wave discharges (SWDs), which are the EEG hallmarks of absence epilepsy, in spontaneously epileptic WAG/Rij rats. Identical findings were obtained in pre-symptomatic WAG/Rij rats (20-24 days of age) and in age-matched non-epileptic Wistar control rats, suggesting that the regulation of GAT-1 by mGlu5 receptors is not restricted to epileptic animals. Our data raise the possibility that activation of mGlu5 receptors controls the incidence of absence seizures by enhancing GABA uptake in the cortico-thalamo-cortical circuitry, thereby restraining the endogenous activation of GABAA and GABAB receptors."

Biosimilar • Epilepsy