Circadian Rhythm Disorder, Migraine, Diabetes Drug

Small molecule compounds that selectively antagonist the photoreceptor molecule melanopsin (Opn4) expressed in retinal ganglion cells. They suppress non-visual light responses and can be used as drugs to improve diseases involving light responses and as research reagents for optogenetics.

Advantages

  • Stronger inhibitory activity than the existing Opn4 antagonist opsinamide (AA92593 reagent)
  • No cytotoxicity and no effect on visual function
  • Local administration such as eye drops is possible

Current Stage and Key Data

  • In vitro : New antagonists inhibited mouse and human melanopsin even in the presence of the Opn4 activator retinal (AA92593 was difficult to inhibit melanopsin in the presence of retinal).
  • In vivo : When the antagonists were administered into the vitreous of human Opn4-expressing transgenic mice, they suppressed the light reflex (pupil constriction). They also alleviated the deviation of the circadian clock and improved glucose tolerance.

Partnering Model

We are looking for partnerships with companies that focus on developing drugs to treat circadian rhythm disorders, sleep disorders, migraines, and diabetes, as well as selling research reagents. We are open to joint research and commercial licensing.

  • Examples of potential partners: Pharmaceutical/biotech or research reagent companies.

Background

Melanopsin (Opn4), a photosensitive protein present in the retina, responds most effectively to blue light and plays a central role in biological responses to light in mammals, including humans. Melanopsin-expressing retinal ganglion cells (mRGCs) are particularly essential for non-visual responses. These responses include pupil constriction upon light exposure, regulation of the circadian clock, sleep, mood, and learning ability, and Opn4 knockout mice exhibit abnormalities in these responses. It has also been reported that melanopsin contributes to the exacerbation of light-induced pain in migraine patients, and that melanopsin-mediated changes in light and dark environments affect blood glucose control. Therefore, melanopsin is expected to be a potential drug target for circadian rhythm disorders, including sleep disorders, migraine, and diabetes.

Patents and Publications

  • Paper submission in preparation, patent pending.

Principal Investigator

Megumi HATORI (Institute of Transformative Bio-Molecules, Nagoya University, Tokai National Higher Education and Research System)

 

Project ID:BK-05305

 

Medicine

Updated
Published

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