Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: T3D Therapeutics, Inc.
T3D-959 is a dual agonist of the peroxisome proliferator activated nuclear receptor delta/gamma, aka PPARδ/γ. It is being developed as an oral therapy for Alzheimer’s disease. In 2013, T3D Therapeutics acquired this compound from DARA BioSciences. In 2010 and 2011, DARA BioSciences had tested DB959 in Phase 1 trials for dyslipidemia and type 2 diabetes, but subsequently shifted its focus to oncology care products.
The PPAR family of proteins help regulate blood sugar and triglyceride levels. PPAR activation affects these measures by boosting insulin sensitivity, and this approach has become a mainstay for correcting insulin resistance in diabetes therapy. The rationale for evaluating PPAR agonists in Alzheimer's is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease, sometimes called Type 3 diabetes (Sep 2006 conference news; de la Monte and Tong, 2014). Unlike other PPAR-targeted diabetes drugs that have been previously evaluated in Alzheimer's, T3D-959 is not a thiazolidinedione.
The peer-reviewed literature contains one preclinical research paper on T3D-959, by scientists affiliated with T3D Therapeutics. It reports a treatment benefit on spatial navigation and memory in rats previously injected with streptozotocin, a pancreatic cancer chemotherapy that poisons insulin-producing beta cells and is used to model diabetes in rodents (Tong et al., 2016).
In July 2015, a Phase 1/2 study began enrolling 36 people with mild to moderate Alzheimer's disease to compare a two-week course of either 3, 10, 30, or 90 mg of T3D-959, taken once daily. This trial does not have a placebo group. It is a biomarker proof-of-mechanism study, in that the primary outcomes are change from baseline of cerebral glucose metabolism as measured by FDG-PET, and change from baseline of functional connectivity between the precuneus/posterior cingulate cortex and hippocampus as measured by resting-state fMRI. The Digit Symbol Substitution Test, ApoE subgroup analysis, blood lipid metabolomics, and ADAS-cog 11 constitute secondary outcomes. Conducted in Florida and South Carolina, this trial is set to run through July 2016.
- de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol. 2014 Apr 15;88(4):548-59. Epub 2013 Dec 28 PubMed.
- Tong M, Deochand C, Didsbury J, de la Monte SM. T3D-959: A Multi-Faceted Disease Remedial Drug Candidate for the Treatment of Alzheimer's Disease. J Alzheimers Dis. 2016;51(1):123-38. PubMed.
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