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Degenerative reitnal disease

Degenerative retinal diseases are caused by genetic mutations (ex., retinitis pigmentosa) or pathophysiological damages (ex., AMD and glaucoma) to the retina. Unfortunately, human retinas do not regenerate, therefore visual loss caused by the diseases remains permanent, although current therapeutic approaches could delay the disease progression.
- Retinitis pigmentosa (RP)

Retinitis pigmentosa is a hereditary retinal degenerative disease. It affects people of all ages, from those who experience vision loss after birth to those who develop symptoms after middle age. Early symptoms include night blindness and decreased peripheral vision, gradually affecting the entire retina, and most people eventually lose most of their vision.

- Age-related macular degeneration (AMD)

Age-related macular degeneration (AMD) is known to be the leading cause of vision loss in old age. As it is caused by degeneration of the macula, located in the center of the retina, central vision is initially blurred and then peripheral vision is gradually lost. It is divided into wet AMD, in which angiogenesis is observed in the macula, and dry-AMD, in which only macular drusen is observed, and dry-AMD accounts for more than 85% of patients. In most patients, dry-AMD eventually develops into wet AMD. In the case of wet AMD, neutralizing antibody therapy against angiogenesis factor (VEGF) is effective, but there is no effective treatment for dry AMD.

- Glaucoma

Glaucoma is a disease in which the optic nerve, which connects the eye and the brain, is degenerated, and is closely related to the increase in pressure in the eye (intraocular pressure). Continued use of eye drops reducing intraocular pressure can delay the progression of the disease. However, there is no effective treatment for patients without increased intraocular pressure.

Retinal Regeneration
The retina of mammals, including humans, cannot be restored once damaged, but the retina of amphibians and fish mostly regenerates after damage. It is known that when the retina of fish is damaged, Müller glia cells regenerate new retinal cells by re-differentiating into neural stem cells. However, reprogramming of Müller glial cell is suppressed in human retina for some reason. We discovered PROX1, a protein that inhibits the reprogramming of Müller glia in the injured mammalian retina, and succeeded in restoring the retina regeneration function of Müller glia by removing this substance. We plan to apply it to retinal degenerative diseases to enable vision recovery through retinal regeneration.

Anti-PROX 1 Antibody (CLZ001)
CLZ001 can capture PROX1 in the extracellular space, where PROX1 moves to Müller glial cells to suppress retinal regeneration. Therefore, CLZ001 therapy can promote reprogramming of Müller glial cells to retinal progenitor/stem cells, consequently resume neuronal regeneration in mammalian retinas.

Homeodomain Protein (HP)
Intercellular transfer is a shared property of HPs, which are identified more than 200 in human. The HPs are known to regulate the growth, differentiation, and regeneration of tissues. The excess as well as the loss of HP cause tissue malformation and degeneration. Therefore, we can supply HPs externally or remove HPs by neutralizing antibodies to cure the diseases caused by HP mal-supplies.