After Civil War Drove Her From Her Homeland, She Went on to Discover the Genes Causing Spinocerebellar Ataxia and Rett Syndrome

As originally reported in Discover Magazine, Huda Zoghbi took an unexpected route to winning the Breakthrough Prize in Life Sciences in 2017 for her discoveries of the genes responsible for two rare neurological disorders. She spent medical school in a city at civil war, sleeping in a small closet in her university basement. While she was in the US that summer, she found herself trapped by closed borders, and she couldn’t go home. She continued on to become a neurologist here, personally developing an expertise in diseases that were still largely misunderstood. Decades later, she emerged triumphant in her dedication to the diseases, the winner of a $3 million dollar prize. She had identified the genes causing spinocerebellar ataxia and Rett syndrome, two crippling and fatal disorders.

From Lebanon to Nashville

Zoghbi grew up in Lebanon and was accepted into American University in Beirut, the most prestigious medical school in the Middle East. Amidst her studies though, civil war beset the country, and her city was hit full force with the violence of the conflict. The danger of moving through the city necessitated her full commitment to her schooling; she had no choice but to spend six months of her studies spending the night in a sleeping bag in a cramped basement of the university, full of medical students unshaken in their drive to understand health.

Living without fresh air and freedom took a toll though, and in the summer, her brother was injured by shrapnel.  Her father wanted to give them space from the violence overtaking their home. They sent her and her brother to spend that summer with cousins they had in the US, and the ultimately joined family in Texas. They didn’t realize then though that by the time the summer was over, she wouldn’t have the chance to go home. The war had destroyed peace in her home, the countries borders were shut, she was shut out. So she began to reinvest her life into the US. It was late in the year to apply to medical schools, but she got entrance into Meharry Medical College, and she was off to Nashville.

She spent her education there before continuing onto her residency in Baylor College of Medicine, where she continues to work now. Here she discovered her passion for neurology when she sampled it in her rotations. She said to Discover magazine:

“It was like a big puzzle, but it had a certain logic to it. And I’ve always liked puzzles.”

Here she was introduced to two young women who displayed what she later learned to be Rett syndrome, which would later became a center of her studies.

Rett Syndrome

Rett syndrome is a rare neurological disorder that primarily affects females and profoundly affects behaviour and development. Though the girls begin to reach milestones, they regress when they are around one year old, often losing fine motor skills, the ability to walk and talk, and cognitive skills. Other symptoms include repetitive hand movements, which are constant while awake, social anxiety, and symptoms appearing like autism.

Zoghbi had two patients come in with extremely similar characteristics. While before Rett syndrome was often lumped in with autism, she thought their similar symptoms must mean it was something else, and genetic. She developed an interest in the disease and began to study it more intensively. Like many rare diseases, it had little research or knowledge surrounding it. She hypothesized it to be genetic disorder because of the commonality between cases, but at the time she was unable to go further than this, as identifying the specific gene abnormality is a much harder question. So she studied molecular genetics, to get to the bottom of the case.

While she had been a practicing expert in pediatric neurology for years, she entered the lab as a freshman. Zoghbi had come into the field with her mind set on Rett syndrome, but she decided to put that to the back burner until she had developed her skills as a researcher. She began her first major project focusing on spinocerebellar ataxia (SCA), an ultra-rare disease that begins to present symptoms when patients are in their 40s. The disease has devastating effects, progressively robbing patients of their ability to balance, speak, swallow, and eventually breathe. While studying this disease, she garnered the skills to understand genetic research, and after eight years in the lab, she emerged with her first major success: her and Harry Orr had found the gene causing SCA. This allowed her to research therapeutic options based on this knowledge.

After that great accomplishment, she was able to return to studying Rett syndrome. Her and researchers in her lab employed these skills. Zoghbi and Ruthie Amir are crediting with finding the Rett syndrome gene causing faulty coding for the MECP2 protein. She was able to take this finding and connect it to other neurological diseases that have mutations in the same gene, including some types of autism, intellectual disabilities, and juvenile schizophrenia. Her findings were the key to unlocking some fixes. Since a Rett syndrome patient would have too much or little of the specific protein, they can work on creating therapies that act on this mechanism.

“It’s been a long haul, and many people told me I was wasting my time, but I’m more convinced than ever of the value of doing basic research. I’ve been at it for 30 years now, and it’s only because of that effort that I can see light at the end of the tunnel—see a path toward interventions that could help my patients with SCA or Rett and other degenerative conditions.” – Huda Zoghbi


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