Nanobody May Lead to Treatment for Retinitis Pigmentosa

A team of scientists from the University of California, Irvine, believe they have discovered a special antibody which may lead to a treatment for Retinitis Pigmentosa, a condition that causes loss of central vision, as well as night and color vision.

The study, Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain, was published in Nature Communications.

Retinitis Pigmentosa (RP) is a group of inherited eye diseases that affect the retina in the back of the eye. It is caused by the death of cells that detect light signals, known as photoreceptor cells. There is no known cure for RP, and the development of new treatments for this condition relies on cell and gene therapies.

UCI researchers have targeted their study on a specific molecule which they believe will provide a treatment for Rhodopsin-associated autosomal dominant RP (adRP). The molecule, Rhodopsin, is a key light-sensing molecule in the human retina. It is found in rod photoreceptor cells, and mutations in the Rhodopsin gene are a primary cause of adRP.

For this study, researchers used a special type of llama-derived antibody, known as a nanobody, that can halt the process of Rhodopsin photoactivation, allowing it to be investigated at high resolution.

Scientists discovered that these nanobodies target an unexpected site on the Rhodopsin molecule, near the location where retinaldehyde binds. They also found that the stabilizing effect of these nanobodies can also be applied to Rhodopsin mutants that are associated with retinal disease, suggesting their use as therapeutics.

Researchers hope to improve nanobodies’ ability to recognize Rhodopsin from other species including mice, for which several pre-clinical models of adRP are available. They also have plans to use these nanobodies to address a long-term goal in the field of structurally resolving the key intermediate states of Rhodopsin from the inactive state to the fully ligand-activated state.

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Sources:

Arum Wu, David Salom, John D. Hong, Aleksander Tworak, Kohei Watanabe, Els Pardon, Jan Steyaert, Hideki Kandori, Kota Katayama, Philip D. Kiser, Krzysztof Palczewski. Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-40911-9

University of California – Irvine. (2023, September 7). Nanobody may lead to treatment for Retinitis Pigmentosa. ScienceDaily. Retrieved September 8, 2023 from www.sciencedaily.com/releases/2023/09/230907105900.htm
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