Alto’s Groundbreaking Biomarker Test Shows Promising Results in Treating Depression

As JP Morgan week kicked off in 2023, Alto Neuroscience was named number seven on BioSpace’s NextGen Bio 2023 list and brought with it positive data from a groundbreaking study of major depressive disorder. The company’s AI-enabled biomarker platform, ALTO-100, evaluates brain function measures such as EEG and computerized behavioral tests to identify patients most likely to respond to their therapies. This enhanced understanding of the brain’s activity, along with their therapies, will be a game-changer in the treatment of depression.

Alto’s Phase IIa study sought to find out if there was a way to predict which patients would respond positively to the innovative therapy ALTO-100, a treatment that seeks to restore the brain’s plasticity. This groundbreaking therapy is believed to provide the brain with the flexibility to adapt to new information. CEO Amit Etkin, M.D., Ph.D. expressed his enthusiasm for ALTO-100’s potential in a recent interview with BioSpace.

ALTO-100 has demonstrated impressive results in treating MDD patients with cognitive issues. Topline data revealed that 61% of patients with a certain biomarker saw a 50% reduction in their depression symptoms, compared to 33% of those without the biomarker. This powerful treatment could be a game-changer for those suffering from MDD and related cognitive issues.

The biomarker-defined patient group saw a remarkable 15.5-point decrease in their Montgomery–Åsberg Depression Rating Scale (MADRS) scores after just six weeks of treatment, far exceeding the 10.6-point reduction seen in the biomarker-negative cohort.

With an encouraging tolerability profile reported in more than 395 patients, the experimental treatment has quickly moved to the next phase of testing. Tuesday marked the start of the Phase IIb study, with the first patient enrolled right away. This marks yet another milestone in the company’s ambitious plans to bring the treatment to the public.

The results of this study could have a major impact on Alto’s development of treatments for this subgroup of responders. By identifying which subgroups would benefit from the therapy, Alto can present the highlights of the data at JPM Wednesday afternoon, potentially revolutionizing the way treatments are developed. Importantly, it would also allow Alto to identify those for whom the therapy would not be effective.

A Paradigm Shift

A revolution is taking place in the field of precision neuropsychiatry. Gone are the days of a trial-and-error approach to treating depression, post-traumatic stress disorder, anxiety disorder and other neuropsychiatric illnesses. Now, a more precise and targeted approach is being embraced, with the hope of delivering more effective results.

When it comes to treatments for various diseases and conditions, our drug arsenal is surprisingly limited. We have biological treatments, but without biomarkers to characterize the patient receiving the treatment, we can’t optimize the effectiveness of these treatments. That’s why biomarkers are so important – they can help us understand the biological makeup of a patient and tailor treatments accordingly. By leveraging biomarkers, we can make a greater impact on the lives of those affected by various illnesses.

Depression is an increasingly common issue in America, with nearly one in ten citizens reporting a depressive episode in 2020, according to research from Columbia University. But Dr. Etkin, a leading expert in the field, believes that this widespread mental health disorder can’t possibly have a single biological cause. He insists that we must acknowledge the complexity of the issue and seek out more holistic solutions.

Drugs are often failing in clinical development, not due to lack of effectiveness, but because the appropriate patients for whom they are effective have not been identified. Alto is leading the charge in this revolution, with a blood test to determine which currently marketed drugs will work best for each individual patient. Joining Alto in this mission is Tel Aviv-based biotech Genetika+, which is also developing a blood test for this purpose.

Genetika+ unites a patient’s genetic and environmental backgrounds to provide a comprehensive picture of their health, utilizing clinical data and patient history. By understanding a person’s genetic makeup, Genetika+ can determine how a drug may impact the body, from the liver to the brain. As Talia Cohen Solal, Ph.D., CEO and co-founder of Genetika+, explains, this insight can “tell [the patient] whether a drug is going to make it past the liver to the brain.”

Using cutting-edge stem cell technology, Dr. Cohen Solal has developed a groundbreaking process for creating a “brain in a dish” for every patient using their own blood cells. By exposing these customized models to different antidepressants, she is able to determine which one will be most effective at improving the effects of the illness on the individual’s brain. High throughput and high content screening are used to identify the ideal treatment option, offering the promise of personalized and highly effective treatments for mental health issues.

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