FP802 dihydrochloride

5xFAD transgenic mice and wild-type littermates^[1]

10 and 40 mg/kg

p.o., daily for 4 months

Showed no apparent adverse effects on the liver, kidney, or heart.
Reduced the complex formation of GluN2B with TRPM4 in the 5xFAD mice at both 10 and 40 mg/kg.
Reduced complex formation of GluN2A with TRPM4 at 40 mg/kg.
Significantly decreased the interaction between NMDAR and TRPM4 without affecting the total protein levels of GluN2A, GluN2B, or TRPM4.
Led to a significant increase in the time 5xFAD mice spent in the target quadrant and the frequency with which they crossed the platform's prior location at the dose of 40 mg/kg, compared to vehicle.
Increased the time 5xFAD mice spent exploring the novel object in the Novel Object Recognition (NOR) test and the displaced object in the Novel Location Recognition (NLR) test relative to vehicle treatment.
Prevented the shift of mitochondrial morphologies from normal to pathological phenotypes in both CA1 and CA3.
Effectively preserved dendritic trees in 5xFAD mice as compared to controls, as demonstrated by increased total dendritic length and numbers of crossings in the Sholl analysis.
Prevented the increase in the density of 'apparent orphaned synapses' in both stratum oriens (CA1 basal dendrites) and stratum radiatum (CA1 apical dendrites) of 5xFAD mice.
Prevented the loss of excitatory and inhibitory synapses and the associated structural deterioration of postsynaptic densities (PSD) in the basal and apical dendrites of CA1 neurons, thereby preserving synaptic integrity in 5xFAD mice.
Led to a 25-40% reduction in Aβ plaque load, significantly limiting plaque development without completely preventing its formation.

Male SOD1^G93A transgenic mice and wild-type littermates^[2]

40 mg/kg

s.c., daily from ~week 15 for 4 weeks

Disrupted he interaction of TRPM4 with the NMDAR subunit GluN2B in mice spinal cord.
Significantly better neurological scores and less body weight loss than vehicle-treated controls.
Significantly improved motor performance (increased total distance traveled and rearing frequency in the open field).
Significantly extended the lifespan of SOD1^G93A mice (survival median increased from 151 to 164 days).
Preserved larger soma sizes of lumbar spinal motor neurons compared to the control group at week 19.
Significantly reduced serum NfL levels while showing no effect on spinal microglial response or EAAT2 expression.
Showed no adverse effects on liver, kidney, heart, or blood counts.