Teen uncovers new weapons to stop Huntington’s disease

WASHINGTON – David Seong, 18, has always been fascinated by the brain. “I like the body,” he says, “but I really thought the brain was the most complex part.” But that interest in the brain really took off during an internship last summer, at Massachusetts General Hospital in Boston, Mass. His mentor, Jong-Min Lee, was focusing on Huntington’s disease. Before long, David was too. This inherited brain disorder creates rogue proteins that can eventually destroy the mind and body. But the senior at Lexington High School in Massachusetts now thinks he might have a solution: Fight the genetic disease with snippets of genetic material.

David was a finalist in the 2014 Intel Science Talent Search. Run by Society for Science & the Public, the annual competition brings 40 of the brightest U.S. high school seniors to Washington, D.C., to show off their research projects.

The first symptoms of Huntington’s disease typically show up when someone is 35 to 44 years old. As the illness progresses, a patient’s body may begin to writhe about. Their movements will become jerky. The disease also can make it hard for someone to speak or swallow. Eventually, the disorder can begin to erase a person’s memories.

Such a large variety of symptoms actually arise from something very small, a change in one gene. Now, David is looking for ways to fight Huntington’s using weapons that are even smaller. They are snippets of genetic material known as microRNAs.

DNA contains all the information our cells need to function. RNA, a related form of genetic material, is also present in nearly every cell. It copies the information in DNA and uses it to make the proteins that run our cells. But there is another type of RNA. It comes in super-tiny segments.  Called microRNAs, they control how RNA translates DNA’s instructions into new proteins.

After RNA copies information from the DNA for a particular gene, that information can be translated into proteins. But if a microRNA comes along and attaches to the end of that RNA molecule, protein production will not take place. David hoped to harness the power of these controlling little microRNAs against Huntington’s disease.

His target was the gene called HTT (for huntingtin). Mutations in it produce a distorted form of an important protein known as huntingtin. This mutant protein cannot perform its normal job in the nervous system, and instead forms large clumps. And over the course of decades, cells with abnormal huntingtin will die, and the devastating symptoms of Huntington’s disease will emerge. David wanted to find the RNA bits that might bind to RNA as it transcribed the mutant HTT gene.

But the human body produces more than 2,000 different types of microRNAs. Any one might interact with HTT. David used a computer to scan through 23 different databases while working in Lee’s lab. Those databases contained information on all known microRNAs and which RNAs they might bind to. As the teen sifted through those records, he found six candidate microRNAs.

Lee’s lab ordered each of those microRNAs from a company. One by one, David incubated each type of microRNA with human embryonic kidney cells. These are a cell type commonly used in biology. Afterward, he examined whether the microRNAs had bound up RNA that had been copying the HTT gene.

David also tested the microRNAs in combinations. If several targeted the RNA that makes huntingtin, then using them as a combo might give the scientists a better chance of slowing the production of the mutant protein. What’s more, high doses of microRNAs might be bad for patients, David says. So finding a group of microRNAs that could be given together — each at a lower dose than when successfully used alone — might reduce any side effects.

The good news: All six microRNA’s that David turned up in his database screening bound the RNA that had tried to make huntintin. They also worked in groups.  But the teen still needs to determine if the combos are more effective than any one microRNA alone.

Treating Huntington’s disease with microRNAs is still a long way off. Those snippets of genetic material need to be tested in human nerve cells, then whole animals and finally in people. That’s how researchers test whether any candidate drug is both safe and effective. But David is hopeful. “Huntington’s is a model neurodegenerative disease in a way,” he says. “It’s just one gene, one mutation, that causes it.” So it’s a relatively simple system to work with. But “if we could do something about Huntington’s,” he believes, “the methods we use could apply to other more complex diseases as well.”

Power Words

human embryonic kidney cells  A line of cells that were removed from a human fetus in the 1970s, and which have been grown in Petri dishes ever since. These cells divide easily and are very popular in cell biology laboratories.

database   An organized collection of information. 

DNA  (short for deoxyribonucleic acid) A long, spiral-shaped molecule inside most living cells that carries genetic instructions. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

gene  A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

Huntington’s disease  A disease caused by a mutation in the gene Huntingtin. It produces memory problems, psychiatric symptoms, uncontrolled writhing movements and other movement symptoms. It begins mildly, usually in middle-adulthood, and becomes more severe over time. Huntington’s disease affects five to 10 out of every 100,000 people, or 0.1 percent of the population.

internship   A training program where students learn advanced professional skills by working alongside experts. People who participate in these training programs are called interns. Some intern in medicine, others in the sciences, journalism or business.

microRNA   Small chunks of RNA, only about 22 RNA “letters” long that serve a regulatory role. These tiny segments of genetic material bind to large RNA molecules, preventing them from being read to create a protein.

mutation   Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.

neuron or nerve cell  Any of the impulse-conducting cells that make up the brain, spinal column and nervous system. These specialized cells transmit information to other neurons in the form of electrical signals.

nervous system  The network of nerve cells and fibers that transmits nerve impulses between parts of the body.

Petri dish   A shallow, circular dish used to grow bacteria or other microorganisms.

RNA    A molecule that helps “read” the genetic information contained in DNA. A cell’s molecular machinery reads DNA to create RNA, and then reads RNA to create proteins.

transcription  (in biology)  The process of making an RNA copy of DNA. Enzymes open the DNA strands at the location of a particular gene. Then RNA forms, joining up to one of the strands and making a copy of it. The cell then uses this copy in a separate process to make a protein.