Ambry Genetics-Led Research Collaboration Clears Path to Understanding Optic Atrophy in Mitochondrial Disease

Ambry Genetics Corporation demonstrated that defects in a gene called FDXR are associated with optic atrophy, or loss of vision, in some patients with mitochondrial disease. The company collaborated with a research laboratory and a children’s medical center to find the disease-causing mechanism and move closer to a possible treatment for the condition.

The study, titled “Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy,” was published in the journal Human Molecular Genetics.

Initially, researchers at Ambry used a special technique called diagnostic exome sequencing (a way of analyzing only the parts of genes involved in protein production) to find mutations in the FDXR gene in 17 patients with optic atrophy and other signs of abnormal mitochondrial function. The gene produces a protein called ferredoxin reductase, which participates in the normal functioning of mitochondria.

“Because this is such a rare mutation, we needed to reach out to other labs to see if the clinical presentation was similar across all available patients,” Deepali Shinde, Ambry researcher, said in a press release. “Without their collaboration, we would not have been able to complete the project.”

In cells from the patients cultured in the laboratory, the effects of the mutation on mitochondrial function could be reversed by supplying them with a normal FDXR gene.

Ambry collaborated with the Jackson Laboratory, a biomedical research institution, and showed that laboratory mice with defects in the FDXR gene experienced loss of vision and impaired gait, much like humans with mutations in the same gene.

“The FXDR mutation in mice revealed an eye disorder phenotype and other complex mitochondrial deficiencies similar to human patients, thus endorsing Ambry’s initial findings,” Jackson Laboratory researcher Dr. Laura Reinholdt said.

Also, Taosheng Huang, MD, Ph.D., the Director of the Program of Mitochondrial Medicine at the Cincinnati Children’s Hospital Medical Center (CCHMC), collaborated with Ambry on multiple-institute studies focused on understanding the disease mechanism in order to develop a treatment. Ambry Genetics reports that the initial results have been promising.

“This is a great collaboration between industry and academic researchers where we are collaborating instead of competing with each other,” Dr. Huang said. “A majority of the FDXR patients die in early childhood; understanding the disease mechanisms will help us develop effective treatments.”

“Not only were we able to help the affected families, we were also able to demonstrate that this research has an impact beyond those affected,” said Ambry scientist and Laboratory Director for Clinical Genomics, Sha Tang. “These findings can play a role in patients’ healthcare management as well as family planning.”