Researchers studying a protein linked to a rare, severe disease have made a discovery that sheds light on how cells meet their energy needs during a severe metabolic crisis. The findings could lead to new treatments for the disease and open new avenues of research for other conditions involving impaired fat metabolism.

When scientists at the Centre for Genomic Regulation (CRG) in Barcelona first identified a handful of protein-coding genes called TANGO in 2006, they had no idea that one of them, TANGO2, would eventually be linked to a life-threatening disorder in children. In 2016, the researchers found that mutations in TANGO2 cause a rare disease now officially recognized as TANGO2 Deficiency Disorder (TDD).

There are about 110 known patients with TDD worldwide, though there are thought to be an estimated six to nine thousand undiagnosed patients in total.

A study led by UMass Chan Medical School researchers has demonstrated that a gene therapy to correct a mutation that causes maple syrup urine disease (MSUD) prevented newborn death, normalized growth, restored coordinated expression of the affected genes and stabilized biomarkers in a calf as well as in mice.

“Simply put, we believe the gene therapy demonstrated in both animal species, especially in the cow, very well showcases the therapeutic potential for MSUD, in part because the diseased cow, without treatment, has a very similar metabolic profile as the patients,” said Dan Wang, Ph.D., assistant professor of genetic & cellular medicine.

Dr. Wang is co-principal investigator with Heather Gray-Edwards, DVM, Ph.D., assistant professor of genetic & cellular medicine; Guangping Gao, Ph.D., the Penelope Booth Rockwell Chair in Biomedical Research, director of the Horae Gene Therapy Center, director of the Li Weibo Institute for Rare Diseases Research and chair and professor of genetic & cellular medicine; and Kevin Strauss, MD, adjunct professor of pediatrics and head of therapeutic development at the Clinic for Special Children in Gordonville, Pennsylvania.

A rare genetic disease that ravages some but spares others has baffled researchers — until now.

Researchers found that a genetic variant, HAQ-STING, acts as a shield against COPA Syndrome, a discovery that could lead to life-changing gene therapies. For families long plagued by the disease, the revelation was both an explanation and a beacon of hope.

A breakthrough in understanding COPA syndrome.