Bipolar disorder disrupts\u00a0daily life, causing severe shifts in mood and energy, flipping between extreme highs and deep lows. Most\u00a0patients\u00a0who are prescribed currently available drugs\u00a0for the condition\u00a0like mood stabilizers\u00a0don\u2019t\u00a0benefit much from them,\u00a0and instead,\u00a0have to\u00a0grapple with side effects from these medicines. The\u00a0demand for\u00a0new\u00a0therapies\u00a0that are\u00a0both effective and\u00a0not associated with significant side effects\u00a0is\u00a0pressing.\u00a0New therapies in the clinic hope to meet this demand.\u00a0<\/p>\n
Current standards of care:\u00a0patient\u00a0needs\u00a0unmet\u00a0\u00a0<\/p>\n
Bipolar disorder affects\u00a0more than 40 million people in the world, and the depressive phase is the predominant and most disabling state for\u00a0the majority of\u00a0patients.\u00a0It causes physical changes in the brain\u2019s emotion control\u00a0centers\u00a0and the chemical messengers, which then disrupt\u00a0how the emotional and thinking\u00a0centers\u00a0communicate. \u00a0\u00a0<\/p>\n
The condition\u00a0is marked by persistent low mood, loss of interest, fatigue, and impaired functioning. Patients lose an average of more than one month of work each year and face elevated risks of hospitalization and suicide.\u00a0\u00a0<\/p>\n
The current standard of care relies\u00a0largely on\u00a0mood stabilizers and atypical antipsychotics, often used in combination,\u00a0explained Kevin Finney,\u00a0president and\u00a0chief executive officer (CEO)\u00a0of Autobahn Therapeutics, a California-based\u00a0neurodrug\u00a0developer.\u00a0\u00a0<\/p>\n
\u201cMore than half of\u00a0the\u00a0patients do not receive adequate relief from currently available therapies, which are limited by modest efficacy and significant side effects, including weight gain, sexual dysfunction, movement disorders, and metabolic complications. For many patients, those side effects compound the very symptoms they are already managing,\u201d said Finney.\u00a0<\/p>\n
He pointed out that this burden is\u00a0evident\u00a0in atypical depression, \u201ca prominent and highly underserved subpopulation.\u201d It is characterized by\u00a0heightened\u00a0appetite, hypersomnia, and low energy.\u00a0<\/p>\n
\u201cSome standard-of-care treatments actively worsen these symptoms, and there has been no fundamentally new mechanism of action approved in bipolar depression in years,\u201d said Finney, whose company is\u00a0developing a treatment for\u00a0the condition.\u00a0<\/p>\n
Autobahn Therapeutics\u2019\u00a0elunetirom\u00a0reaps positive clinical results\u00a0<\/p>\n
Autobahn\u2019s\u00a0elunetirom\u00a0is an oral, once-daily, brain-targeted thyroid hormone receptor agonist, which acts as a central nervous system (CNS)-selective thyroid hormone receptor beta agonist.\u00a0\u00a0<\/p>\n
\u201cIt is designed to do something different from essentially every antidepressant developed over the last 40 years,\u201d said Finney.\u00a0<\/p>\n
Rather than modulating neurotransmitters like serotonin, dopamine, or norepinephrine, Finney explained that\u00a0elunetirom\u00a0targets thyroid hormone receptors in the brain to boost cellular energy and drive neuroplasticity, the brain\u2019s ability to form and strengthen connections. In other words, it is designed to help restore healthy brain function rather than simply manage symptoms. As\u00a0currently approved treatments tend to not be\u00a0efficacious enough\u00a0or have\u00a0poor tolerability\u00a0in\u00a0patients, these unmet needs are what\u00a0elunetirom\u00a0is designed to address.\u00a0<\/p>\n
It is\u00a0similar to\u00a0the neuroplasticity mechanism\u00a0that psychedelics<\/a>\u00a0follow, Finney explained. \u201cIt is the same pathway behind much of the excitement around psychedelics.\u201d\u00a0<\/p>\n The difference, however, is that the drug comes\u00a0with no psychoactive effects and,\u00a0it being a once-daily oral tablet, there is no treatment burden as\u00a0patients can take it at home without having to\u00a0make frequent\u00a0visits to\u00a0the clinic.\u00a0<\/p>\n Synthetic thyroid hormones\u00a0have\u00a0been used\u00a0off-label\u00a0in depression for more than 50 years, which offer decades of human evidence that this pathway matters in mood.\u00a0\u00a0<\/p>\n \u201cThe underlying biology is not new,\u201d said Finney. \u201cWhat has been missing is a way to access that benefit in the brain without the peripheral effects of thyroid hormone, such as effects on the heart. That is the problem\u00a0elunetirom\u00a0is built to solve: bringing the benefit of thyroid hormone biology to the brain while limiting activity in the rest of the body.\u201d\u00a0<\/p>\n Topline results\u00a0from a phase 2 study in 21 patients\u00a0shed some light on the drug\u2019s benefit.\u00a0Patients were given\u00a0elunetirom\u00a0along with their usual treatment regiment, which\u00a0comprises\u00a0mood stabilizers and antipsychotics. The candidate\u00a0was found to successfully reduce depression severity in patients with bipolar disorder. About 75% of patients responded to the treatment after six weeks and 50% of them were in remission by then. A statistically significant 16.8-point\u00a0Hamilton Depression Rating Scale (HAMD)-17 improvement was observed, hitting the primary endpoint of the study.\u00a0The\u00a0HAMD-17 is a test used to measure the severity of depression in patients and to check how well\u00a0a\u00a0treatment is working.\u00a0\u00a0<\/p>\n \u201cFor the millions of people living with bipolar depression who have not found adequate relief, these recently reported data offer real encouragement,\u201d said Finney. \u201cJust as important, we saw the onset of statistically significant improvement as early as week two, which points to a rapid antidepressant effect. And\u00a0elunetirom\u00a0was safe and well-tolerated, with no severe or serious treatment-related adverse events.\u201d\u00a0<\/p>\n Patients improved across the symptoms linked to atypical depression, including energy, sleep, and appetite, which are the areas that today\u2019s treatments often make worse, Finney pointed out.\u00a0<\/p>\n \u201cThe patient-reported measures told the same story,\u201d he\u00a0said. \u201cThe functional recovery was just as striking.\u201d\u00a0<\/p>\n Patients reported feeling \u201csignificantly better\u201d based on the Patient Global Impression and the Symptoms of Depression Questionnaire.\u00a0Quality of life improved too.\u00a0Patients\u00a0who entered the study\u00a0were losing\u00a0an average of 2.7 days of work each week. This dropped to 0.4 days after six weeks of taking\u00a0elunetirom.\u00a0<\/p>\n \u201cFor people who have lived with this illness for years, restoring that much daily functioning is profound,\u201d said Finney.\u00a0<\/p>\n Meanwhile,\u00a0Israeli company\u00a0Syremis\u00a0Therapeutics\u00a0launched\u00a0with $165 million late last year to tackle\u00a0depression\u00a0associated with\u00a0bipolar disorder, major depressive disorder<\/a>, and schizophrenia.\u00a0Its candidate\u00a0for bipolar depression, however,\u00a0is an NMDA receptor antagonist.\u00a0ST-901, which is in the investigational new drug (IND)-enabling stage, is meant to work by blocking\u00a0the NMDA (N-methyl-D-aspartate) receptor. This receptor\u00a0controls\u00a0glutamate levels \u2013 the brain\u2019s main\u00a0excitatory neurotransmitter.\u00a0By regulating glutamate, ST-901 could prevent its overactivation, thereby resetting brain chemistry in depression.\u00a0<\/p>\n Targeting glutamate: RAP-219 for mania\u00a0<\/p>\n Mania is a core symptom of bipolar disorder.\u00a0It affects the brain by hyper-activating the\u00a0amygdala, the\u00a0emotional\u00a0center\u00a0of the brain,\u00a0and dulls the prefrontal cortex, which\u00a0is responsible for\u00a0judgement and impulse control. As dopamine tends to spike during manic episodes, the\u00a0amygdala\u00a0goes into overdrive.\u00a0\u00a0<\/p>\n Rapport Therapeutics\u2019 RAP-219\u00a0is designed to target the TARP\u03b38 protein, a helper protein attached only to AMPA receptors\u00a0in specific parts of the brain. These AMPA receptors respond to glutamate. Once RAP-219 binds to a specific part of the receptor, it changes the shape\u00a0so as to\u00a0dial down overactive brain signals.\u00a0\u00a0<\/p>\n Topline results of a phase 2 trial are expected later this year, after which the company hopes to engage in talks with the U.S. Food and Drug Administration\u00a0(FDA)\u00a0to potentially design a phase 3 program and plan for a new drug application to treat bipolar mania.\u00a0<\/p>\n Also in phase 2 trials is\u00a0ALTO-100. Developed by Alto Neuroscience in California,\u00a0ALTO-100\u00a0is another\u00a0oral small molecule\u00a0that is designed\u00a0to\u00a0enhance\u00a0neural plasticity in the hippocampus, a brain region important for both cognition and mood.\u00a0According to the company, it builds on\u00a0the understanding\u00a0that depression is in part driven by a reduction in hippocampal\u00a0neuroplasticity<\/a> and\u00a0is\u00a0targeted to those patients who\u00a0lack\u00a0this\u00a0neuroplasticity,\u00a0which is\u00a0the brain\u2019s ability to rewire and build new connections.\u00a0\u00a0<\/p>\n ALTO-100 is currently in\u00a0phase 2b development for the treatment of bipolar depression\u00a0on top of the standard of care.\u00a0Topline results are expected\u00a0this year.\u00a0<\/p>\n With\u00a0trials\u00a0ongoing, it looks like 2026 will be a year\u00a0of\u00a0pivotal readouts\u00a0for potential bipolar disorder treatments.\u00a0Elunetirom\u00a0leads\u00a0the charge\u00a0with its encouraging phase 2 results, as well as\u00a0its recent Fast Track Designation from the FDA.\u00a0<\/p>\n Finney foresees a path\u00a0for\u00a0elunetirom\u2019s\u00a0approval. He said: \u201cWith a strong bipolar dataset in hand and major depressive disorder data coming later this year, we believe\u00a0elunetirom\u00a0has the potential to become a franchise-defining treatment across multiple forms of depression.\u201d\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"Bipolar disorder disrupts\u00a0daily life, causing severe shifts in mood and energy, flipping between extreme highs and deep lows.…\n","protected":false},"author":2,"featured_media":551036,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[2996,103,61,60,18649,16944],"class_list":["post-551035","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-clinical-trial","tag-health","tag-ie","tag-ireland","tag-mental-health-issues","tag-small-molecules"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/551035","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=551035"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/551035\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/551036"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=551035"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=551035"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=551035"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}