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T3D Therapeutics’ drug explores the link between diabetes and Alzheimer’s disease

There’s a growing consensus that two of society’s most rampant public health issues – Type II Diabetes and Alzheimer’s disease – are intertwined. It’s not all about clearing plaques anymore: Insulin modulation is askew in both diseases, which has led researchers to examine sugar metabolism’s link to cognitive decline. North Carolina startup T3D Therapeutics is actually repurposing a […]

There’s a growing consensus that two of society’s most rampant public health issues – Type II Diabetes and Alzheimer’s disease – are intertwined. It’s not all about clearing plaques anymore: Insulin modulation is askew in both diseases, which has led researchers to examine sugar metabolism’s link to cognitive decline.

North Carolina startup T3D Therapeutics is actually repurposing a small molecule drug that was initially being developed for diabetes, and aiming it instead toward Alzheimer’s.

“The similarities of insulin resistance between Type 2 diabetes and Alzheimer’s disease are very striking,” CEO John Didsbury said. After all, they’ve both got amyloid aggregation, oxidative stress, inflammation, neural degeneration and cognitive impairment. Didsbury’s got a grand vision for the efficacy of the small molecule drug: He projects T3D’s once-a-day pill could “slow, stop or reverse the course of Alzheimer’s disease.”

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T3D just received a $1.8 million federal grant to get its experimental Alzheimer’s disease therapy on its legs. It’s otherwise raised another $1.8 million from angel investors since its 2013 launch, and will need about $1 million more in the foreseeable future, Didsbury said.

The drug’s wrapped up phase 1 trials. It’ll use the funding to help support a Phase 2a trial that will test the startup’s lead compound, T3D-959, on 36 patients with mild-to-moderate Alzheimer’s disease.

Didsbury describes the drug as “a nuclear receptor agonist that regulates a myriad of genes involved in energy metabolism, and memory and learning pathways.” It can regulate the WNT pathway, which is vital in memory and learning, and can overcome insulin resistance in the brain, he said.

“The hallmark of Alzheimer’s disease is really low sugar metabolism in the brain,” Didsbury said. “This is actually a better predictor of cognitive decline than amyloid plaque or tau bundle loads.”

The order of operations, he said, goes: Brain insulin resistance can cause increased toxicity of beta amyloid. This, in turn, causes tau alternation that leads to the tangles, which can cause oxidative stress that leads to inflammation, which can cause neuronal cell death.

The small molecule drug is being licensed from DARA Biosciences, at which Didsbury previously served as chief scientific officer. DARA was directing the drug towards diabetes, but the company pivoted away from that indication and into oncological sales. Didsbury said he left DARA and started T3D – with Alzheimer’s in mind.

“I know the molecule exquisitely well,” Didsbury said. “I was putting two and two together, and it kept adding up to 20 for Alzheimer’s disease.”

The drug’s perfectly effective, after all, in treating diabetes, Didsbury said. But there’s a huge difference in the markets. When it comes to pill popping, he argues that diabetes is an area of low unmet medical need. Plenty of drugs on the market do the job just fine. Additionally, there are enormous regulatory hurdles in play when developing a diabetes drug – large cardiovascular outcome trials need to be done, which add to the cost of development significantly. One can be much more lithe in developing an Alzheimer’s drug, he said, as it represents more of an unmet need.

[Image courtesy of stock.xchng user raZna]