Twins with rare genetic disorder could hold clue to cure for Ebola

Chris Hempel has spent the last eight years fighting for the lives of her twin girls. Her 10-year-old daughters, Addi and Cassi, both have Niemann-Pick Type C, an incredibly rare hereditary disease that's caused primarily by mutations in the NPC1 gene, which is responsible for the body's ability to metabolize lipids.

"This gene is critical," Hempel told CBS News. "If it's nonoperational, it's catastrophic. As a result of it not even working they have childhood Alzheimer's."

To help their daughters, Hempel and her husband, Hugh, have gone far beyond the measures most parents could ever imagine. They've spent years contacting any doctor or scientist that might be of help to their family and started a foundation to raise money for Niemann-Pick research. Most remarkably, the couple -- whose story was featured last year in the Wall Street Journal -- worked with doctors, researchers, the National Institutes of Health, the U.S. Food and Drug Administration and the Niemann-Pick community to fast-track a Phase 1 clinical trial for a drug Chris Hempel helped to create.

But one thing Hempel never imagined was that her family would end up in the middle of some of the most promising scientific research on Ebola.

It's estimated that there are currently just 500 known cases in the world of Niemann-Pick Type C, a neurodegenerative condition that causes delay and loss of cognitive and motor function, neurological problems and seizures. The disease causes a harmful buildup of lipid proteins in organs including the spleen, liver, lungs, bone marrow and brain, and eventually proves fatal; patients usually die before they reach adolescence. Addi and Cassi began to show signs of Niemann-Pick at age 2. Despite receiving exceptional care, their health continues to decline, said Hempel. They have regular seizures and both are unable to walk or talk.

Out of necessity, the Hempels, who live in Reno, Nevada, became involved in the scientific community for rare diseases, which typically is severely underfunded. "When our twins were first diagnosed we wanted to give a lot of ourselves," said Hempel. "We were getting requests from researchers who wanted to study the cells of children like mine."

But scientists studying rare diseases weren't the only ones interested in Addi and Cassi's DNA. Virologists wanted it as well. It turns out two rare diseases -- one viral and one genetic -- are connected in an unexpected way.

In 2011, Hempel received a Google news alert on a story from Science Daily about a new study published in the journal Nature: "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1." In other words, a person without a functioning NPC1 gene appears to be incapable of catching the Ebola virus.

In the paper, the researchers noted the skin cells for their study had come from the Coriell Institute for Medical Research, a biobank and independent non-profit organization for human genomics in Camden, New Jersey. Several years before, Hempel had donated skin cells from Cassi and Addi to Coriell for scientists to use in lab-based research.

"I read the articles and instantly realized that the cells used in the Ebola experiments were from kids and families like mine," she said. "My first thought was 'holy cow' followed by a strange visual of our cells floating around in petri dishes with the Ebola virus and people suited up in Hazmat suits."

She emailed Dr. Kartik Chandran, associate professor of microbiology and immunology at Albert Einstein College of Medicine in the Bronx, N.Y., a coauthor of the study, to request a copy of the paper and learn more about his research.

Chandran, who has been studying Ebola for a decade, has for the last five years focused his research on how the virus uses the NPC1 gene as a receptor to infect human cells. Through his work, he's discovered that once the virus has entered into the cell membrane it latches on to the protein made by the NPC1 gene. But if cells do not produce the protein -- due to a mutation in this gene -- the virus cannot enter the cells. Similar research has also found AIDS and the Marburg virus also exploit the protein made by the NPC1 gene.

"They try to infect my twin' cells with Ebola and AIDS, and they can't infect them," Hempel said of virologists who have studied the NPC1 gene. "Their cells are on lockdown. Their NPC receptor doesn't even work."

As is the case with the more than 20,000 genes that make up the human genome, every person has two copies of the NPC1 gene. Both copies of Addi and Cassi's NPC1 gene have mutations, which causes Niemann-Pick disease. Hempel and her husband each have one functioning NPC1 gene and the other with mutations. The disease that afflicts the Hempel girls is a result of both parents passing on their mutated copies.

Though her daughters appear to be Ebola-resistant due to their genetic makeup, Hempel said subsequent research has indicated that she and her husband, with one mutated gene, are also probably more likely to survive the virus compared to the general population.

Chandran's studies back this up. In one study, Chandran and his team gave Ebola to mice that had mutations in both copies of the NPC1 gene and another control group with two working copies of the gene. He found the mice without NPC1 mutations died from Ebola within a week of infection, whereas the mice with faulty copies of the gene did not get sick. In another study, soon to be published, Chandran added a third group of mice that had one working copy of the gene and one with mutations. That group of mice still became ill when they were infected with Ebola, but they recovered much faster and survived.

"In those mice there's some kind of advantage that helps their immune system mount a very effective defense," Chandan told CBS News. He conducted his Ebola research in partnership with other institutions, including the U.S. Army Medical Research Institute of Infectious Diseases, Netherlands Cancer Institute and Harvard Medical School.

Chandran said he hopes his research will lead to the development of drug that uses NPC1 to stop an Ebola infection.

"What we're trying to do is develop small molecule therapy that would incapacitate the gene temporarily, and then take them off the drug and everything goes back to normal," he said.

Hempel believes the drug Chandan hopes to develop could also benefit patients with Niemann-Pick since the ability to "turn on" the NPC1 gene could effectively cure the disease. However, Chandran says he doesn't want to create any false expectations -- especially since an Ebola drug that targets this gene will take years to develop.

But Hempel says she is hopeful, and her work has already come full circle. In a number of lab experiments cyclodextrin, the drug she helped to develop and which her daughters currently take, effectively killed the AIDS virus in petri dishes. A clinical trial of the drug on AIDS patients will soon to be underway at the University of California Davis School of Medicine.

"It's so mind-boggling that I can hardly express how I think about it in my mind and heart and what it feels like to be able to part of something this far reaching to advance research," said Hempel. "It also provides me a sense of relief from a terrible burden that I carry from giving my children this gene that is killing them. I am starting to piece together the puzzle as to why we have this gene in the first place."