“That's what this drug is doing, it's getting you back on your game. It's refeeding the brain that is being starved in Alzheimer."
T3D-959, a dual peroxisome proliferator activated receptor (PPAR) delta/gamma agonist with 15-fold higher PPAR delta potency, was studied in 36 patients with mild-to-moderate Alzheimer disease. Subjects were randomized to 1 of 4 doses of T3D-959 daily for 14 days—3 mg, 10 mg, 30 mg, or 90 mg—assessed for safety and tolerability, and evaluated for changes from baseline in cerebral metabolic rate of glucose (FDG-PET imaging), functional connectivity of the hippocampus (BOLD-fMRI) and cognitive function (ADAS-Cog11 and DSST).
The results show multiple signals of efficacy, Didsbury notes, from changes in the metabolome, changes in glucose metabolism in the brain, and improvements in cognitive testing. FDG-PET results demonstrated changes in brain glucose uptake in a dose-dependent fashion and may increase relative glucose uptake in needed regions of the brain. The cognitive evaluation by ADAS-Cog11 demonstrated that all ApoE4-negative patients improved 4.8–6.1 points at low and mid (3 mg–30 mg) doses, while ApoE3-positive patients improved 1–3.5 points at mid and high (30 mg–90 mg) doses. DSST results revealed an average improvement of 2.4 points in subjects with moderate Alzheimer and 7 points in subjects with mild Alzheimer regardless of the dose or genotype.
Didsbury adds that T3D-959 is essentially treating Alzheimer disease as a chronic anorexia of the brain because the brain is not receiving the energy needed—a result of insulin resistance.
After the completion of the phase IIa trial, a phase IIb will be underway where subjects with mild-to-moderate Alzheimer disease will be dosed with T3D-959 for 6 months. Researchers will assess cognitive performance and look at glucose metabolism in the brain using FDG-PET brain scans.