Subscribe to eTOC

Sidney Carter Award Lecturer: Rose Mary Boustany, MD: On Mysteries of Pediatric Neurogenetic Disorders



Dr. Rose Mary N. Boustany discusses her path toward work on neuronal ceroid lipofuscinosis.

Growing up in Beirut, Rose Mary Boustany, MD, and her sister used to tag along with their father, a general physician, on Sunday home visits. “That attracted me to medicine at a young age,” she said.

From her earliest days in medical school at the American University of Beirut (AUB), and in her pediatric neurology residency at Massachusetts General Hospital, Dr. Boustany — now the director of the Neurogenetics Institute at AUB — found herself fascinated with the brain, and particularly the brains of children.

The need for more pediatric neurologists became clear to her in medical school at AUB. “At the time, there was not a dedicated pediatric neurologist,” she recalled. “The adult neurologists filled in. They were great, and I loved neurology because of them, but there was a gap, and I wanted to fill it because I loved working with children.”

Her first few cases had unusual pediatric neurologic problems, and that solidified her interest. “I treated a little boy with adrenoleukodystrophy, and I figured it out and was so proud of myself,” she said. “The abnormalities in the long-chain fatty acids hadn't yet been described, so it was very much a clinical diagnosis. But it was the correct one.”

Toward the end of her training at Mass General, Dr. Boustany took note of the early explosion in genetics, and felt that she needed to be stronger in that field. “I did a fellowship in neurogenetic disorders and the die was cast. I've been in this field ever since.”

As a clinician at heart, Dr. Boustany wasn't drawn to basic research, but in her work at Mass General, she soon found herself frustrated. “I was always trying to get colleagues to work on something I was interested in, but they wouldn't do it. So I said, I'm going to have to do this myself,” she recalled. After nine years in Boston, she joined the faculty at Duke University School of Medicine as an assistant professor. When not on service, she stipulated that she wanted to work like a post-doc and learn DNA sequencing.

“Two years later I was writing my own grants and had my own lab,” she said.


During her time at Mass General, Dr. Boustany had become intrigued by neuronal ceroid lipofuscinosis (NCL), often called Batten disease, a group of at least 14 genetically distinct neurodegenerative disorders with excessive accumulation of lipopigments (lipofuscin) in the tissues. The infantile, late infantile, juvenile and other forms of NCL differ primarily in age of onset and duration, but they all involve deterioration of vision, seizures, and eventual death, with the infantile form leading to death by about age four, the late infantile form by around early adolescence, and the juvenile form by the mid-20s.

She first encountered NCL while doing fellowship training with Edwin Kolodny, MD, now professor emeritus of neurology at New York University Langone Medical Center in New York.

“I co-directed a lysosomal storage diseases laboratory with him,” she says. “But we'd also get these requests from clinicians who'd just send in urine and blood and a brief summary of the cases, and I had to choose what tests to do.” Those tests, she found, often led to a diagnosis of late infantile or juvenile NCL.

“It's probably the most common neurodegenerative disease of children, more common than metachromatic leukodystrophy or things like that, especially in the aggregate,” she said. “There is quite a bit of NCL, as far as rare diseases go, but at the time I came upon it we knew so little. At the time we didn't even know if one or many genes were involved, how many forms there were, and the obscurity attracted me. I cared for two kids who carried the diagnosis and got so attached to those initial patients, and then I met other patients at a family gathering at the Shriver Center for Mental Retardation.”

The first grant Boustany ever wrote, while still in Boston, was for an attempt to identify genes associated with the NCLs. That was funded in January 1987. In 1995, together with the Harvard group and others, Dr. Boustany identified the first known gene for NCL, the gene for the juvenile variant. Since then, at least 14 genes and more than 150 mutations have been linked to NCL.

Now, she hopes to make the leap toward developing therapies for this incurable group of diseases.

“I have two related patents, both of them using drugs developed for something else as a treatment for NCLs, and that's one area I'm discussing in my lecture,” she says.

Another topic of her lecture is a bit of an accidental discovery made while studying one of the NCL genes. “I had read that sometimes the same genes involved in neurodegeneration also play a role in cancer, so I started studying the antiapoptotic gene CLN3, the gene defective in the juvenile form of Batten disease, in the context of oncology. Our team at Duke discovered that it was CLN3 that was also upregulated in certain cancers. We've determined that it's actually an excellent biomarker for cancers, particularly breast cancer, an area I am working on here at the American University of Beirut — so I also work on breast cancer.”

Five years ago, Dr. Boustany returned to her native Lebanon. “It was always a dream of mine to return home, even though I had resigned myself that I was too involved in my lab and my students and my life in the US,” she says. “But AUB made me an offer I couldn't refuse.”

Since then, she has added another area of pediatric neurology to her plate: autism. “I'm still at the beginning, but we're trying to identify autism susceptibility genes in the Lebanese population,” she says. “So there are now three main projects in my lab, but my primary interest is neurogenetic disorders and dual disabilities in children. At the end of my career, I would like to be able to say that what I did made a difference in the health of neurologically impaired children — that I made their lives just a little bit better.”