Anti-nausea drug reduces Alzheimer's-advancing astrocytes in mice, biotech says

A recent announcement from Hoth Therapeutics highlighted the promising results of their drug candidate, HT-ALZ, in a mouse model of Alzheimer’s disease. The company, utilizing the anti-nausea molecule aprepitant, has found significant reductions in astrocyte coverage in the brain, alongside improvements in cognitive function.

The hippocampus, a brain region commonly affected early in Alzheimer’s, showed notable decreases in astrocyte coverage with both 20-mg and 40-mg doses of HT-ALZ compared to control groups. This reduction was not only confined to the hippocampus but also observed in the cortex. The decrease in astrocytes was linked to enhanced cognitive abilities in the treated mice, suggesting the drug’s potential in mitigating some of the disease's detrimental effects.

Astrocytes, star-shaped cells crucial for brain immunity and neuron maintenance, play a dual role in Alzheimer’s. While some astrocytes help break down harmful amyloid beta plaques, others exacerbate the condition by secreting amyloid beta themselves. Hoth Therapeutics’ HT-ALZ, derived from aprepitant—a molecule that binds to the neurokinin 1 receptor and has been FDA-approved since 2003—appears to rebalance this dynamic.

Aprepitant, known commercially as Emend and used to prevent nausea and vomiting in chemotherapy patients, is now showing potential beyond its original application. By reducing the area of the brain covered by reactive astrocytes, HT-ALZ is not only presenting a novel approach to Alzheimer's treatment but also improving cognitive outcomes in experimental models.

Reactive astrocytes, which respond to Alzheimer's and other neurological issues, are larger and often contribute to the disease's progression by producing toxic byproducts. These cells, in their reactive state, attempt to break down amyloid beta into urea, inadvertently facilitating the disease. Preliminary evidence from Hoth Therapeutics indicates that treatment with HT-ALZ results in fewer reactive astrocytes compared to untreated controls.

The drug’s development as an oral soluble film, as detailed on Hoth’s website, suggests a user-friendly administration method, potentially enhancing patient compliance. This innovative delivery could make HT-ALZ a convenient option for patients, provided it progresses successfully through clinical trials.

Hoth Therapeutics' CEO, Robb Knie, expressed optimism in their September 17 release, noting the significant reductions in astrocyte activity and the associated cognitive improvements as pivotal points in their development process. This confidence reflects the broader potential impact of HT-ALZ on Alzheimer’s treatment paradigms.

Currently, Hoth is delving deeper into whether HT-ALZ treatment affects the size or total number of astrocytes. Initial findings indicate that treated mice exhibit a lower number of reactive astrocytes compared to controls, which could be a critical factor in the drug’s efficacy.

In summary, Hoth Therapeutics’ HT-ALZ shows considerable promise in addressing Alzheimer’s disease by targeting astrocyte activity and enhancing cognitive function. With its origins in an established anti-nausea medication, this drug candidate may offer a new pathway for treatment, pending further research and validation in clinical settings.