Aug 4, 2020

4D Molecular Therapeutics Launches Phase 1 Clinical Trial for Choroideremia Gene Therapy

Eye On the Cure Research News

Gene therapy delivered by intravitreal injection

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Gene therapy developer 4D Molecular Therapeutics (4DMT) has dosed the first patient in its Phase 1 gene therapy clinical trial for people with choroideremia, a progressive, vision-robbing inherited retinal disease. The trial will enroll 15 patients at two sites: Retina Foundation of the Southwest in Dallas and the Moran Eye Center, University of Utah, in Salt Lake City. While the primary goal of the study is to evaluate safety, investigators will also look for evidence of efficacy.

4DMT’s emerging choroideremia gene therapy is administered through an injection into the vitreous, the soft gel in the middle of the eye. Intravitreal injections are less invasive than the subretinal injections frequently used to administer gene therapies. The injection of 4DMT’s choroideremia gene therapy contains human-engineered viral containers that deliver healthy copies of the REP-1 into retinal cells to augment the mutated copies of REP-1 that cause cell and vision loss.

4DMT uses a process known as directed evolution in the design of its adeno-associated virus (AAV) gene delivery systems to maximize effectiveness and safety. Directed evolution involves the creation of millions of different AAV containers — also known as capsids— for penetrating cells with the therapeutic genetic cargo. The capsid that can penetrate cells best and minimize safety and resistance risks is then selected to use in the treatment of humans.

“4DMT is highly innovative in its approaches to designing and developing gene therapies,” says Brian Mansfield, PhD, executive vice president for research and interim chief scientific officer at the Foundation Fighting Blindness. “We are pleased to see their gene therapy move into human studies and look forward to reports for safety and efficacy.”

4DMT is also conducting preclinical studies for X-linked retinitis pigmentosa (RPGR mutations) and wet age-related macular degeneration.

Choroideremia is an X-linked inherited retinal disease causing progressive vision loss, primarily in males. Females are usually unaffected carriers of the disease, but are sometimes affected, as well. Choroideremia affects multiple cells types in the retina including the choroid, a layer of vasculature in the outer retina. Choroideremia also leads to loss of photoreceptors, the cells that make vision possible, and the retinal pigment epithelium which provides support for photoreceptors.

Roche, a global pharmaceutical company, is partnering with 4DMT to clinically and commercially develop its emerging gene therapies.