Sometimes, big discoveries come from unexpected places.

Such is the case with Mitchell syndrome, an ultra-rare orphan disease discovered by Houston Methodist researcher Hyunglok Chung, Ph.D. that may prove to be the key to unlocking secrets of common diseases like multiple sclerosis (MS), Alzheimer's disease and Huntington's disease.

Dr. Chung specializes in using fruit fly models to diagnose and develop therapeutics for rare human diseases. Prior to joining the Houston Methodist Department of Neurology in 2023, he was a pivotal member of the Undiagnosed Disease Network as a postdoctoral fellow in the lab of renowned Baylor College of Medicine researcher Dr. Hugo Bellen.

Over the course of six years, Dr. Chung and his colleagues published over 20 papers and helped identify 12 rare genetic diseases, including Mitchell syndrome. Named after Mitchell Herndon — the first person to be diagnosed with the disorder and suffer its fatal effects — Mitchell syndrome causes a progressive loss of mobility, motor control, hearing, vision and cognitive function. So far, it has only been identified in 25 patients.

While investigating potential therapies for Mitchell syndrome, Dr. Chung discovered that myelin breakdown results in an accumulation of very long-chain fatty acids (VLCFA) in the brain that can cause brain cell-damaging inflammation. If lipid accumulation could be reduced, treatment could be applicable to other diseases.

In a study published in Cell Metabolism, Dr. Chung and colleagues 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 caught the attention of Dr. Jun Li, chair of the Department of Neurology at Houston Methodist. Dr. Li recruited Dr. Chung to Houston Methodist to establish a lab studying neuroinflammation as well as a Drosophila functional core, neither of which existed previously at the hospital.

"The fly gene is easy to manipulate, and we can generate a mutation with no ethical issue," said Dr. Chung. "It is quick, and about 70 percent of human disease-causing genes are found in flies. The model is gaining more and more appreciation these days."

It is also easy to get fruit fly studies approved by the FDA, helping to accelerate investigations on rare genetic diseases. When a clinician sees a patient who cannot be diagnosed, geneticists can analyze the whole genome or whole exome sequence to find variants likely to be pathogenic. The case can then be assigned to a model organism researcher like Dr. Chung to assess for phenotypic similarities to the patient.

"Lots of neurological phenotypes in humans can be assessed in fruit flies, including seizure, motor skills, aging and neuroinflammation," explained Dr. Chung.

Chung will continue working on the fly model and helping rare disease patients at Houston Methodist, but he will also 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.

To learn more about Dr. Chung and the impact of his work on Mitchell syndrome, check out the full Methodology article here.