{"id":41654,"date":"2012-12-18T00:00:00","date_gmt":"2012-12-18T06:00:00","guid":{"rendered":"https:\/\/www.unmc.edu\/newsroom\/2012\/12\/18\/a-bright-smile-drives-genetic-research\/"},"modified":"2022-08-29T14:33:42","modified_gmt":"2022-08-29T19:33:42","slug":"a-bright-smile-drives-genetic-research","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/newsroom\/2012\/12\/18\/a-bright-smile-drives-genetic-research\/","title":{"rendered":"A bright smile drives genetic research"},"content":{"rendered":"

\nTammy Kielian, Ph.D., turned to the computer in her office and pulled up a picture of childhood joy: a young girl with glasses, with a sunbeam of a smile, the kind that reaches into your chest.<\/p>\n

\n“This is Olivia,” Dr. Kielian said.<\/p>\n

\nDr. Kielian, a professor of pathology and microbiology in the College of Medicine, beamed a little herself.<\/p>\n

\n“She’s a pistol,” Dr. Kielian said, then stopped, and looked at the picture again.<\/p>\n

\nThis is why she works now. This is why she does what she does.<\/p>\n

\nOlivia, the go-getter, the girl with the indefatigable smile, is Dr. Kielian’s 9-year-old niece; her sister’s youngest kid.<\/p>\n

\nA while ago they noticed Olivia’s vision was getting worse.<\/p>\n

\nShe went through two pairs of glasses before her family could blink.<\/p>\n

\nA second-opinion suggested it might be the first sign of something else, and it was. Genetic testing confirmed Olivia has juvenile neuronal ceroid lipofuscinosis, better known as<\/p>\n

\nJuvenile Batten disease. It’s inherited, autosomal recessive, neurodegenerative. That was a little over a year ago.<\/p>\n

\nJuvenile Batten occurs in about one in 100,000 live births, Dr. Kielian said. That’s very rare — but it still adds up to plenty of kids. That’s a lot of families that will mark time in two ways — from the day before they heard the diagnosis and the day after.<\/p>\n

\n“It changes everything,” Dr. Kielian said.<\/p>\n

\nLook at that picture again.<\/p>\n

\nBasically: Mutation of the gene CLN3 results in lysosomal storage problems. An abnormal amount of protein and lipids become trapped inside the cells. Like when the garbage disposal breaks, the body can’t clean the clog.<\/p>\n

\nAs the material accumulates in brain cells, neurons in the central nervous system begin to die. The first symptom is loss of vision. Then seizures. Then cognitive loss, then motor loss. Then premature death.<\/p>\n

\nA lot of kids who have it are gone by their late teens.<\/p>\n

\nFor the past dozen years or so, Dr. Kielian’s lab has investigated immune responses in the brain. She had an idea that maybe this had something to do with it; maybe her research might have an impact. She had to try.<\/p>\n

\nDavid Pearce, Ph.D., an expert in the field, has published 60 papers on Batten. Dr. Kielian emailed the director of the Sanford Children’s Health Research Center in Sioux Falls, S.D., and proposed a collaboration. Almost immediately, her computer dinged with his reply. Then her phone rang, too.<\/p>\n

\nDr. Pearce was excited. In this much unexplored field, her approach was novel.<\/p>\n

\nCall it fate, coincidence — whatever.<\/p>\n

\nHer research expertise was in line to make an impact on this disease.<\/p>\n

\nSoon, Dr. Pearce’s mouse models — mice with mutated CLN3 genes, just like in these kids — were headed to UNMC.<\/p>\n

\nAnd in these mice, Dr. Kielian found that the two types of brain cells she studies — the microglia, the brain’s first line of defense, and the astrocyte, which supports neuron viability — are activating early. Very early.<\/p>\n

\n“We believe that when these cells turn on early, they inadvertently contribute to an environment that, down the road, leads to neuron death,” Dr. Kielian said.<\/p>\n

\nScientists see it all the time: sometimes our antibodies work against us.<\/p>\n

\n“An overactive immune system may be contributing to this disease’s pathogenicity,” Dr. Pearce said.<\/p>\n

\nNow, one of the goals in the study of Juvenile Batten is to slow down this process to give these kids more years and better ones.<\/p>\n

\nDr. Kielian hopes — along with investigators grateful for the fresh perspective — that her work will inspire other researchers.<\/p>\n

\nMeanwhile, Olivia is doing it all with abandon. She’s in gymnastics and Girl Scouts. She’s learning braille. Her mom has her in everything, has her breathing life in with great gasping gulps.<\/p>\n

\nLike Olivia ever had a problem with that.<\/p>\n

\nThere are good days and there are bad.<\/p>\n

\nKids who have Juvenile Batten disease can sometimes rage against the dying of the light or they can seem detached.<\/p>\n

\nThis awful thing steals them, neuron by neuron. Sometimes parents don’t even tell their kids they have it. Sometimes that’s for the best.<\/p>\n

\nOlivia understands that someday she may not see. Right now, that’s what she knows.<\/p>\n

\nDr. Kielian asked her sister and her husband if there was anything they didn’t want her to talk about for this story. No, they said. Say everything.<\/p>\n

\n“Seizures will initially be controlled by medication,” Dr. Kielian said. “Eventually they won’t.”<\/p>\n

\nNow, a catch in her voice: “Cognitive loss will occur.”<\/p>\n

\nDr. Kielian soldiered on: “Speech will go. She won’t really be able to communicate anymore. She’ll be in a wheelchair. After that, bedridden. And then the end.”<\/p>\n

\nSilence.<\/p>\n

\nOne second. Two …<\/p>\n

\n“Strangely enough, it doesn’t seem real right now,” Dr. Kielian said.<\/p>\n

\nNo, of course it doesn’t. Right now, she’s doing something. Right now, she’s getting funding, and readying proposals for more. Right now, she’s making presentations at national conferences and investigators are praising her new ideas.<\/p>\n

\nRight now, her sister is seeing this — her sister is going to conferences, too, meeting the scientists who are so hard at work.<\/p>\n

\nRight now, their fight has only just begun.<\/p>\n

\nBut this is different. This isn’t in theory.<\/p>\n

\nThis isn’t your typical investigation. This isn’t abstract.<\/p>\n

\nThey are on the clock.<\/p>\n

\nShe nodded at the assessment, repeated it with a whisper: “We’re on the clock.”<\/p>\n

\nBut science doesn’t work like that. Research moves at its own pace; and Dr. Kielian has to detach herself — as a professional and a scientist. Her lab knows this story, of course. And she might mention her niece in an opening sentence at a conference. But, there is no picture of Olivia and her sunbeam smile in the lab or at presentations. There is no impassioned plea. There can’t be.<\/p>\n

\nResearch doesn’t work like that.<\/p>\n

\nInstead, all she can do is push her sadness into a box and use it as fuel. And she does. And she will. This is what she’ll work on forever.<\/p>\n

\n“And I will always do it for her,” she said. Always, for that go-getter girl with the smile you can feel in your chest.<\/p>\n

\n“Always,” Dr. Kielian said. “That will never change.”<\/p>\n<\/div><\/div>","protected":false},"excerpt":{"rendered":"

A 9-year-old with Juvenile Batten disease
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