The dopamine agonist pramipexole could help restore the ability to feel pleasure in patients with mood disorders, supporting Alto Neuroscience’s investigational depression drug that uses the same active compound, according to an independent study conducted by a Swedish university, as announced on June 16.
The randomized, double-blinded and placebo-controlled PRIME-PRAXOL study was conducted at Lund University in Sweden. It enrolled more than 80 patients diagnosed with major depressive disorder, bipolar depression or dysthymia. The study focused on pramipexole, a dopamine agonist known for its antidepressant effects across the brain. Pramipexole is already approved as Boehringer Ingelheim’s Mirapex for Parkinson’s disease and restless leg syndrome.
Alto Neuroscience is developing ALTO-207, an investigational treatment that combines fixed doses of pramipexole with the antiemetic ondansetron. According to Alto, this combination—currently being tested in mid-stage trials—allows higher doses of pramipexole at a more rapid titration by preventing side effects that would otherwise limit dosing.
Results from the independent study were published in Nature Medicine and showed that pramipexole significantly improved anhedonia scores measured by the Snaith-Hamilton Pleasure Scale (SHAPS), which assesses how much pleasure patients derive from daily activities. The study also found stronger benefits for patients with major depressive disorder compared to those with dysthymia. Improvements were maintained throughout six months of observation.
Jefferies told investors on Monday that Alto “is looking to disrupt the [central nervous system] paradigm by leveraging precision psychiatry” through its use of biomarkers during development, Jefferies said. It expects Alto's stock could “move significantly higher” if any Phase 2b readouts next year deliver promising results. Several mid-stage studies are underway for ALTO-207 across multiple indications including major depressive disorder and bipolar depression; a pivotal Phase IIb dataset in treatment-resistant depression is expected in late 2027.
