Sanford Research lab director Kevin Francis, Ph.D., discovered his love for science when he dissected a frog and shark during high school anatomy class in West Virginia.
“The intricacies of how different systems are connected and how one system affects another just blew me away,” Dr. Francis said.
So he studied biology and chemistry in college, then learned about neurodevelopment and diseases of the nervous system while earning his Ph.D. at The Medical University of South Carolina. He became involved with rare diseases of the nervous system during a postdoc at the National Institutes of Health.
In 2015, Dr. Francis brought that interest to Sanford Research, where a key focus is on rare diseases affecting children.
“It’s a really unmet scientific need,” he said. Children affected by the diseases he studies have a severely diminished quality of life and often early lethality.
Learn more: How CoRDS rare disease registry gives hope and impacts research
Families with a child who has this type of rare disease find a glimmer of hope in research like Dr. Francis’. And that makes his research more meaningful than simply studying cells and molecules. He knows the names of individual children who could be affected by his results. He gets regular updates from their families about how they’re doing and how other research efforts are going.
“That brings a whole other sense of urgency to the research,” Dr. Francis said.
And when he gets a grant to support his research, like a recent award of $83,718 from a family foundation for a yearlong project on the lysosomal storage disorder Batten disease, he feels a special sort of gratitude.
“These families have worked really hard to fundraise money to give to my group to do that research,” he said. “So I’m thankful to them for that … and hopeful that what we do find will translate for some of these kids.”
Batten disease steals skills, then kills
Batten disease is a rare, inherited, fatal neurological disorder for which no cure exists. Symptoms for most forms of Batten disease begin in childhood, according to the National Institutes of Health. They can include loss of vision, seizures, delay and loss of skills, dementia and abnormal movements. The symptoms progress over time, robbing children of the ability to move, communicate, think — and eventually to even survive.
About two to four in every 100,000 children in the U.S. are believed to have a form of Batten disease, the NIH estimates.
Parents of a child with Batten disease each carry a gene causing the disease, with a one in four chance of their child inheriting the disease. More than a dozen variants of Batten disease exist, ranging in severity, age of emergence and rate of progression.
Several labs at Sanford Research conduct studies on Batten disease. Dr. Francis’ lab looks at a variant of Batten disease called CLN6, named after a gene that directs a protein of the same name. Symptoms of children with this variant typically show up after they are a few years old, the NIH says. Most children then die in late childhood or early teen years.
Part of the work in Dr. Francis’ lab focuses on genes that affect how cells break down nutrients and small molecules. When functioning properly, enzymes in the lysosomes, which are organelles within the cells, act as a cleaning crew for the cell. But when a gene mutation disrupts that cleaning process, materials accumulate within the cell and lead to diseases collectively called lysosomal storage disorders.
Batten disease is among those.
“It’s extremely detrimental to cell health and tissue function and overall human health,” Dr. Francis said.
His lab seeks to understand why the CLN6 gene is especially important in some cell types. Specifically, they’re looking at the gene’s role in nervous system cells, particularly astrocytes, about which less is known. They want to know how signal interactions between cells happen.
Aiming to save kids
There is currently no FDA-approved treatment to prevent symptoms of Batten disease from appearing, or to stop or reverse the effects of Batten disease once symptoms do appear. But research has focused on trying to develop therapies to replace mutated genes or to provide the proteins that aren’t working properly.
“Everything we’re trying to do now is, once we have a child who is diagnosed with Batten disease, what can we do to either stabilize their symptoms or ideally reverse the symptoms?” Dr. Francis said.
The grant Dr. Francis’ team received will allow them to spend a year diving deeper into some of their promising preliminary work.
They’ll use a couple of certain molecules, or compounds, that target a specific protein that regulates how proteins fold inside a cell. The pharmaceutical company that developed these compounds, Anavex, has developed others, too, that are in clinical trials for other diseases.
Dr. Francis’ lab aims to see how the compounds affect different types of nervous system cells. They also want to see if the compounds could slow the progression in their mice models that mimic the disease, how they might do that, and whether they can lengthen lifespan.
“I’m hoping working with Anavex can prove to be beneficial for Batten disease patients,” Dr. Francis said. “Maybe we could also use this as kind of a model project that we can apply to other rare diseases as well.”
The grant comes from a foundation named for Charlotte and Gwenyth Gray, sisters in California who were diagnosed with Batten disease in 2015 at ages 4 and 2. Their parents, Gordon and Kristen Gray, began the foundation along with fundraising efforts to support research in the hope of improving outcomes for children with Batten disease, including their own.
Career of seeking therapies
Dr. Francis’ hope for his work on this grant is to move a promising compound into an early phase clinical trial for some children with Batten disease.
Dr. Francis’ hope for his career is to change the fate of people facing a rare disease diagnosis.
“I got interested in working with rare diseases because there’s so little we understand about them, and there are only a handful that really have true therapies,” he said.
Someday, he’d like to look back on a career that looks like this: “I made some kind of a definable impact. Maybe I’ve helped us understand how human development works a little bit better … or ideally I’ve found some kind of a therapy for a disease or two or 10,” Dr. Francis said.
“And I’ve been able to help people.”
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Posted In Children's, Genetics, Neurology, Research, Sanford Stories