OTI breakthrough discoveries in glaucoma disease

The trabecular meshwork (TM) located at the front of the eye between the cornea and sclera, and at the drainage angle near the iris is a porous 3D spongelike structure, responsible for 85-90% of the aqueous outflow exterior drainage and the remaining 10-15% outflow exits through the uveal track. Similar to blood pressure, intraocular pressure (IOP) is synchronized with the cardiovascular heartbeat with diurnal variance. In non-glaucoma eyes, the diurnal IOP fluctuation ranges between 3-5mmHg. In glaucoma eyes, the IOP diurnal fluctuation becomes irregular with random spikes, and high frequency of such random spikes, imposes a metabolic stress on the retinal ganglion cells (RGC) located at the back of the eye. The IOP diurnal irregularities in patients with glaucoma are caused by the pressure sensor functional irregularities, underpinning the pressure sensing cell loss or metabolic stress.   Figure adapted from Minimally Invasive Glaucoma Surgery, 2021 at the courtesy by Prof. Keith Barton.  

 Illustration of the pressure sensor anatomy and structure. The pressure sensor is the chief regulator of IOP, composed of pressure sensing cells and the underlying basement membrane, similar in relation to RPE and its underlying Bruch’s membrane. Like RPE and cornea endothelium cells, the pressure sensing cells derive from the neural crest during embryonic development, lack of self-renew in adulthood. The pressure sensing cell loss reaches to a certain threshold (unknow, e.g. 60% loss), patients become poor or non-responders to current IOP lowering medication at which point an invasive 40 mechanic drainage surgery (e.g. tube shunt) becomes inevitable, however that fails at 50% in 5 years. Therefore, the pressure sensing cell loss is the culprit of the RGC loss in the back of the eye in patients with glaucoma. Early intervention to protect the pressure sensor from damage and preserving the pressure sensing cells is of strategic importance.    

Figure adapted from Clin Exp Ophthalmol. 2022 at the courtesy by Prof. KE Keller and Prof. DM Peters. The content discovery in this diagram re: pressure sensor as IOP chief regulator is patented, Inventor; Tina Guanting Qiu. US Publication #US2024/00024348A1 and PCT 1 # PCT/18/356,875. Title: methods and compositions for treating glaucoma and related conditions. US publication on Jan 25th 2024.

 OTI-2024 is adenosine A1 receptor agonist, has dual MOAs via a fast mode vascular effect and a slow mode of MMP therapeutic. It contains two different drugs in one molecule, alike two sides of one coin, one side is the IOP lowering drug (no longer important), the other side is the MMP therapeutic agent, which offers the first cure for treating glaucoma blindness. 

OTI-2024 represents a new MMP platform therapy to offer the first curative solution for treating non-responders in advanced stage glaucoma  due to its superiority of clinical safety and MMP therapeutic potency.  It has the potential to fully  stop the vision loss through MMP trabecular meshwork rejuvenation for early to moderate stage glaucoma.