John Didsbury, PhD

“We feel that by reestablishing metabolic homeostasis, you can effectively treat mild to moderate Alzheimer.”

John Didsbury, PhD, Founder and CEO of T3D Therapeutics, Inc., spoke with 

 at the 2018 Alzheimer Association International Conference in Chicago, Illinois, about T3D’s desire to go against the grain and trend in the therapeutic development for mild to moderate Alzheimer disease.

Didsbury detailed that while much of the medical community has given up—or at least determined it highly unlikely to be successful&mdash;on developing treatments for patients in the later stages of the disease pathology, T3D is determined to develop a drug for them, hoping to reestablish an equilibrium in the brain’s glucose metabolism. The company’s current investigative therapy, T3D-959, is somewhat of an embodiment of that sentiment.

The 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, with data presented at the conference. Didsbury said that thus far, the therapy has shown signs of efficacy, and ultimately, seeks to address a dysfunction in glucose and lipid metabolism in the brain.

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The founder and CEO of T3D Therapeutics, Inc., spoke about T3D’s desire to go against the grain and trend in the therapeutic development for mild to moderate Alzheimer disease.

John Didsbury, PhD: Going Against the Grain in Established Alzheimer

“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."

John Didsbury, PhD, Founder and CEO of T3D Therapeutics, Inc., sat with 

to speak to the final results of the phase IIa exploratory and feasibility clinical trial of T3D-959 in patients with mild-to-moderate Alzheimer disease. The results were presented by Didsbury at the 2018 Alzheimer’s Association International Conference in Chicago, Illinois.

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&mdash;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.

Study results suggest that agonist stimulation of PPAR delta may be an effective therapeutic strategy to addressing dysfunctional metabolism in Alzheimer disease.

John Didsbury, PhD

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John Didsbury, PhD: Going Against the Grain in Established Alzheimer

John Didsbury, PhD: Phase IIa Trial of T3D-959 in Mild to Moderate Alzheimer Disease