Highlights: 

  • Vertigoheel improves visual, spatial, and olfactory memory in aged rats and cognitively impaired mice. 
  • Treatment with vertigoheel stimulates the branching of neurons, which ehances brain connectivty. 

Humans become increasingly susceptible to cognitive impairment (CI) with age, eventually facing difficulties with memory, attention, reasoning, and problem-solving skills. To date, limited therapies for CI exist, as the underlying mechanisms driving CI have yet to be elucidated fully. Due to the lack of available treatments for CI, scientists have leveraged pre-existing drugs to expedite the development of potential treatments. 

Accordingly, in a new study published in Frontiers in Neuroscience, researchers from Germany investigated the potential cognitive-protective effects of the drug vertigoheel, which has a well-established safety record. Ott and colleagues showed that treating cognitively impaired mice and aged rats with vertigoheel enhances memory and cognition across multiple behavioral tests, including the novel object recognition (NOR) test, the T-maze test, and the Morris water maze (MWM) test. Additionally, the investigators found that vertigoheel treatment leads to increased growth of neurites, neuron structures vital to memory formation and storage. 

Vertigoheel Boosts Memory and Cognition

To evaluate the effects of vertigoheel on cognitive function, Ott and colleagues employed a series of behavioral memory tests in aged rats and CI mice, whose impairment was induced via injection with scopolamine hydrobromide – an agent commonly used to model cognitive decline. The tests demonstrated that treatment with vertigoheel successfully boosts multiple features of cognition, including visual recognition memory, working spatial memory, and olfactory memory. 

The most significant results were seen in the T-maze test, which assessed the rodents’ spatial learning and memory abilities as they navigated a T-shaped maze, providing insights into their decision-making processes and memory retention. First, the investigators allowed CI mice to explore the maze freely; however, one arm of the maze was closed, leaving CI mice with only one arm to explore. Then, the German research team allowed CI mice to re-explore the maze with both arms open and calculated the number of times (spontaneous alternations) they entered the newly opened arm. 

Since mice have a natural proclivity to explore unfamiliar areas, Ott and colleagues determined that more spontaneous alternations indicated improved memory. Accordingly, CI mice treated with vertigoheel had significantly higher spontaneous alternations than untreated mice, suggesting that vertigoheel enhances spatial memory and learning. 

(Ott et al., 2023 | Frontiers in Neuroscience) Vertigoheel improves spatial memory. Untreated CI mice (grey) have the fewest spontaneous alternations, indicating impaired spatial memory. Spontaneous alternations are significantly higher in those treated with increasing doses of vertigoheel (SCO+VH-04) and donepezil (a positive control), indicating improved spatial memory. (q.d., daily; b.i.d., twice a day)

Vertigoheel Improves Neuron Health

Normal cognitive function cannot exist without healthy neurons, as they form the intricate networks responsible for processing and transmitting information within the brain. Among the several factors sustaining neuron health, neurites are at the top of the list. These neuronal structures are not only paramount to memory formation but also the communication between neurons. With this in mind, Ott and colleagues sought to determine whether vertigoheel’s cognitive protective effects stemmed from cellular changes in neurites. 

To examine vertigoheel’s effect on neurites, the investigators harvested neurons from the hippocampus – the brain region responsible for learning and memory – and treated them with vertigoheel in vitro (in a dish) at varying concentrations. Moreover, the investigators assessed neurite outgrowth, specifically measuring neurite length. The results showed vertigoheel significantly stimulated neurite outgrowth, with treated neurons exhibiting longer neurites than untreated neurons. These findings suggest that vertigoheel’s cognitive protective effects are potentially linked to increased neurite outgrowth. 

(Ott et al., 2023 | Frontiers in Neuroscience) Vertigoheel stimulates neurite outgrowth. Hippocampal neurons treated with vertigoheel (concentration 3:1) for 7 days exhibit greater elongation of neurites than vehicle-treated neurons (not treated with vertigoheel), indicating increased neurite outgrowth.

Repurposing Drugs to Advance Aging Therapeutics

The development of novel therapeutics is a long, arduous, and costly process that, unfortunately, limits the scope of available treatments for several diseases, like CI. In efforts to accelerate drug development and advance drug innovation, scientists have explored harnessing existing therapeutics, like vertigoheel, with extensive safety and pharmacological profiles to treat conditions with minimal existing therapies. In this study, Ott and colleagues successfully treated cognitive impairment with the pre-existing drug vertigoheel, demonstrating that repurposing drugs for conditions with unmet medical needs, particularly those tied to aging, is a promising avenue that can bring innovative longevity treatments to the market faster.