Repurposed TLR4 inhibitor (TAK-242) to block inflammatory signaling after ischemic stroke.
- Non-surgical treatment of ischemic stroke.
- TAK-242 has shown to be well-tolerated in clinical trials.
- Inhibits the release of multiple cytokines mediated by TLR4.
Stroke can affect people of all ages, including children. Many people with ischemic strokes are older (60 or more years old), and the risk of stroke increases with age. Stroke is the leading cause of disability and the third leading cause of death in the United States. More than 700,000 persons per year suffer a first-time stroke in the United States, with 20% of these individuals dying within the first year after the stroke. If current trends continue, this number is projected to reach 1 million per year by the year 2050. Current treatments for ischemic stroke involve either a small treatment window after injury (<3 hr) or surgical intervention, therefore there is a considerable unmet need for new, more effective and safe therapies.
A growing body of evidence suggests that in situ inflammatory responses are induced in brain tissue and significantly contribute to the brain injury in ischemic stroke, and inhibitors or blockades of inflammatory responses attenuate ischemic brain injury. Toll-like receptors (TLRs) are a family of signal transduction molecules that are critical for the induction of immunity and in host defense. TLR4-mediated signaling has been implicated in the pathogenesis of ischemic injury in the heart, liver, kidney, lung and brain and it has been observed that modulation of TLR4 inhibits inflammatory response in ischemic brain and attenuates ischemic brain injury. TAK-242, is a novel small molecule that selectively inhibits TLR4-mediated signaling from the intracellular domain of TLR4, and inhibits various kinds of inflammatory mediators induced by the activation of TLR4.
In vivo cytokine inhibition and neurological performance data in mice are available.