FDA-approved drug holds promise for children with genetic disease

In the nearly five decades since Mucolipidosis Type IV, or ML4, was first identified, children with the disease have had little promise of ever having a “normal” life. ML4 generally strikes their nervous system early and hard. Most never learn to walk or talk and have a maximum mental capacity of about 18 months. By their teen years, the disease steals their eyesight, and by their 20s, their life is at stake. But just in the past few months, research using an already FDA-approved drug is giving parents like Randy and Caroline Gold of Atlanta hope. “I think that this drug is the first of many treatments that will be available to kids with ML4,” Randy Gold said. “We are incredibly excited because it is the first opportunity to treat a kid affected by ML4.” Gold is president of the Mucolipidosis Type IV Foundation, an international nonprofit focused on funding research directed at understanding the genetic disease and developing treatments. The Golds’ 10-year-old daughter, Eden, was diagnosed with ML4 in 2009. The couple haven’t been shy about soliciting donations for the foundation to help fund research or talking about their experiences caring for Eden. They’ve been on the front lines since 2012 doing what they could to not only improve Eden’s life but the lives of all kids with ML4.

They first shared their story here last summer. At the time, the Golds simply wanted to raise awareness about nonprofit they founded called J-Screen, which makes comprehensive saliva-based genetic carrier screening accessible affordable across the United States. As this year’s ML4 International Research Conference approached late last month, Randy Gold reached out again, excited about the promise of this new research. He knows the drug is not going to instantly turn Eden into a “typical” kid; that she is not going to wake up tomorrow and get herself dressed for school. And yet, it’s hard not to be excited about this first treatment. “We’re certain more treatments will have to follow,” Gold said. “Unfortunately, this drug is not one and done.” According to Dr. Rebecca Oberman, executive director of ML4 Foundation, ML4 is a lysosomal storage disorder where wastes that would normally be degraded removed from healthy cells accumulate in cells throughout the body, causing particular damage to the brain, central ner- vous system, and retina. One of the first effects of this disease is widespread neurological inflammation throughout the brain, which the another and instead and amplifies many of cogWith funding from the nitive and motor problems foundation, researchers in children. Neuroinbe an test ng the drug flammation has been iden- a year ago in mice cells, tified as an early and signif- then expanded to do more icant aspect of ML4 disease advanced testing to validate and is also present in many their findings. The results diseases. were published in the May ML4 researchers at Masissue of The Journal of sachusetts General HospiHuman Molecular Genetics. tal discovered that FingoliFurther testing is now mod, a drug that is already being done in a bigger study approved by the FDA for of live mice, with study treatment of multiple scle- results expected late this rosis in appears to year. reduce this neuroinflamma“This is the first time with tion in ML4 cells and also to this disease that we have a restore neurons, which were drug that shows a level of resnot functioning due to the cue, taking a cell and return- buildup of cellular waste it to a healthier state,” matter, back to a more nor- Oberman said. “If the results mal function. from the mouse study are as these other children, the g ing i and other places across the U.S. and Just in past three years, foun- dation has funded nearly $1 million in research with another $5 million funded positive as we hope, it could by the National Institutes mean a clinical trial in kids of Health. with ML4 in 2019, giving us Oberman created a model the first opportunity to treat for the oundation that kids requires scientists to work that the FDA agrees will have collaboratively, which she a positive impact on them. believes leads to treatment It’s not a cure, but it will treat options being discussed that a major symptom of this disotherwise would not have ease, neurological inflamma- been on table. tion. I can’t tell you now what Indeed, almost every day it will look like in each indi- she is on a conference call to vidual child, we know move from idea to research this is treating laboratory. that is a significant part of In this case, Oberman said, this disease.” one scientist mentioned What shouldn’t be lost in possibility of a drug com- this is the ML4 Foundation pound that should be tested, is based here in Atlanta and another had the ability to do is the engine fostering much the testing, and once that of the research internation- was done, another could ally in Israel, Italy, Boston do genetic analysis of the these with something but something Europe. the f the the the cells, and still another could look at the gene expression of those cells. “In under a year, this group of researchers from Georgia Tech, Harvard and the Weizmann Institute in Israel a paper based on their collaborative data showing Fingolimod was effective,” Oberman said. extraordinary level of research is what we need to be able to go to the FDA and say we need to use this in children.” And that’s not all. Many treatments for major diseases are found by studying rare diseases like ML4, Oberman said, noting researchers studying ML4 see lessons for diseases like Alzheimer’s that also exhibit neuroinflammation. That’s huge. Not just for kids suffering with ML4, but for the rest of us. published “That other

PHOTOS CONTRIBUTED BY BETH INTRO PHOTOGRAPHY Dr. Rebecca Oberman, ML4 Foundation executive director, runs a discussion among parents of children with ML4 at a conference in Atlanta. She says a drug being tested could provide “the first opportunity to treat these kids with something that the FDA agrees will have a positive impact on them.”