Over the years, there has been a growing awareness of the links between thyroid hormones and mood disorders, particularly depression. Autobahn Therapeutics, a pioneer in this field, is harnessing this relationship by developing a novel treatment aimed at enhancing the efficacy of depression medications when traditional antidepressants fall short.
Autobahn’s breakthrough centers around the targeted use of thyroid hormone receptors. Historically, physicians observed that patients on hormone replacement therapy for underactive thyroid glands, also known as hypothyroidism, often experienced an unexpected lift in mood. Psychiatrists then began prescribing thyroid medication to patients whose depression didn’t sufficiently respond to standard antidepressant treatments alone.
The thyroid hormone, which is crucial in regulating metabolism, can be problematic when administered as a synthetic variant to individuals who don’t necessarily have deficient thyroid levels. Autobahn CEO Kevin Finney points out that conventional synthetic thyroid hormones can lead to elevated thyroid hormone levels, increasing the risk of cardiovascular issues among other side effects. To circumvent these risks, Autobahn has developed a small molecule, ABX-002, designed for precise targeting. This molecule selectively acts on thyroid hormone receptor beta solely within the brain, which could potentially elevate mood without the systemic side effects associated with broader thyroid hormone elevation.
ABX-002 stands out due to its method of administration and selective activity. It is a prodrug, meaning it remains inactive until it crosses into the brain and is metabolized into its active form by specific brain enzymes. This targeted approach aims to benefit mood regulation processes without influencing other parts of the body. Early trials have shown promise with ABX-002 proving safe and well-tolerated among participants, and preliminary signs of efficacy in mood regulation.
Autobahn’s approach, based on the foundational science by co-founder Thomas Scanlan at Oregon Health & Science University, marks a significant advancement in targeting thyroid hormone receptors for treating mood disorders. The drug’s development is funded through substantial financial backing, including a substantial $100 million obtained to advance ABX-002 into mid-stage clinical trials focused on major depressive disorder and bipolar disorder depression.
This venture into neurological applications represents a strategic pivot for Autobahn. Initially launched in 2020 with a focus on neurological conditions like multiple sclerosis (MS) and adrenomyeloneuropathy, which involve myelin deterioration, Autobahn previously explored using thyroid hormone beta receptor activation for stimulating regenerative processes in nerve sheaths. However, as of 2022, the focus shifted to leveraging this technology for addressing treatment-resistant depression.
Autobahn’s explorations extend beyond depression treatment. A newer compound, ABX-101, also utilizes their brain-targeting technology but aims at modulating sphingosine 1-phosphate (S1P) receptors, marking another promising avenue particularly for immunologic and inflammatory neurodegenerative disorders including MS. This aligns ABX-101 with other S1P modulators already approved for various medical conditions, with Autobahn’s iteration potentially offering enhanced brain-specific receptor targeting.
The financing for these innovative developments is robust, with significant contributions coming through a Series C round led by Newpath Partners and including various prestigious entities like Canaan Partners, Monograph Capital, and Insight Partners among others. This new influx of capital is expected to propel the preclinical research necessary for advancing ABX-101, alongside the ongoing clinical trials for ABX-002.
Autobahn Therapeutics’ advancements represent a considerable move in addressing some of the most challenging aspects of mental health treatment and neurodegenerative diseases. By more accurately targeting the interplay between thyroid hormones and brain function, Autobahn is paving the way for potentially transformative treatments in psychiatric and neurological care.
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