From The Humble Fly, Great Discoveries Are Made

Currently, treatment only suppresses the progress of the condition. The issue, Chung says, is antioxidants can’t penetrate the blood-brain barrier, and once the phenotype reaches the brain, it cannot be stopped. Chung has discovered that N-acetylcysteine amide (NACA), a blood-brain barrier penetrating antioxidant, can suppress the symptoms in the Mitchell Syndrome fly model. Chung, Bellen, Tiphanie Vogel, MD and Robert Bucelli, MD, PhD, are currently team-up with Nacuity, a pharmaceutical company for NACA, applying with the Federal Drug Administration (FDA) for the compassionate use of NACA to treat the syndrome’s patients. The Herndon family began The Mitchell and Friends Foundation, which provides support to families and research of the disease named for their son. Chung is the foundation’s scientific advisor. In early June, the foundation held its first summit at Houston Methodist. The foundation presented a $25,000 check to Jun Li, MD, PhD, the John M. O’Quinn Foundation Presidential Distinguished Chair in Neurology, Professor of Neurology and Chair of the Stanley H. Appel Department of Neurology at Houston Methodist, with more coming to support Chung’s ongoing research. The power of gathering and networking among the patients’ family is powerful, and they are trying to raise a fund to support research in Mitchell Syndrome using a different platform such as Tiktok. In researching a follow-up question to the Mitchell Syndrome, Chung teamed up with Hyun-Kyung Lee’s lab at Baylor College of Medicine and discovered that myelin breakdown results in an accumulation of VLCFA in the brain that can cause inflammation that damages brain cells. If lipid accumulation could be reduced, treatment could be applicable to other diseases, such as MS. Their research showed that reducing the levels of VLCFA and S1P had a beneficial effect on MS pathologies in a preclinical model, revealing a more effective treatment for MS patients. This work has been recently published in Cell Metabolism. Thus, research into an ultra-rare disease with little funding proved that no disease should go ignored. This work caught the attention of Li at Houston Methodist, and Li wanted to bring Chung to Houston Methodist, where he could establish a lab studying neuroinflammation as well as a Drosophila functional core, neither of which existed previously at the hospital. In March, Chung joined Houston Methodist as an assistant professor at Department of Neurology and also appointed as a director of Drosophila functional core at Houston Methodist Research Institute.

The fly model is also easy to get FDA-approved drug screening in a short time. This makes the model perfect for the work of rare genetic disease studies. When a clinician sees a patient who cannot be diagnosed, the human geneticists step in and analyze the whole-genome sequence or whole-exome sequence of the patient, allowing them to discover the types of variants that patient has and likely to be pathogenic. Then, the case is assigned to a model organism researcher, like Chung, who studies the neurologic phenotype of the fly to determine if the variant is pathogenic and if there are any phenotypic similarities to the patient. Lots of neurological phenotypes in human can be assessed in fruit flies, including seizure, motor skills, aging and neuroinflammation. Chung will continue working on the fly model and help rare disease patients with fly modeling here at Houston Methodist. But this will only occupy half of his time. The other half will be dedicated to determining the unexplored role of lipid metabolism in neuroinflammation. “My ultimate goal is to open new therapeutic inroads into branches of rare and common neurodegeneration research using a fly model,” said Chung.