This article first appeared in the St. Louis Beacon, April 03, 2011 - As Dr. Timothy Miller bicycles from his home in Clayton to his lab at the Washington University Medical School, it's safe to assume he's sometimes thinking about the broad potential for his medical research.
An example involves therapy to "erase" mutations or mistakes in cells with too much protein. The cells become toxic, short-circuiting the normal way that they interact with other cells to carry out routine body functions. Symptoms of nerve cells gone wrong because of the protein imbalance include slurred speech and tremors and the wasting away of muscles and minds. The possibility of erasing the mutations to correct neurological disorders is an example of 21st-century medicine that Miller and many scientists think is within reach.
Far-fetched? To ordinary minds perhaps. But not to Miller. He's among researchers moving such possibilities a step closer to reality. His specialty is ALS, commonly called Lou Gehrig's disease, and he hopes to succeed in using a compound to lower the protein in a gene, called SOD1, that is associated with some forms of ALS. He's just beginning the first of three clinical trials to test the therapy on humans. Success is several years off, but this work is generating much excitement here and nationwide.
"We proved that we could lower the level of protein in mouse and rat models. All the data this far suggested that if we lower the level of protein, that's beneficial to people. As soon as we found out that we could lower the level of this toxicity in protein in people, we were thrilled about doing it. We realized this could be a way to treat this form of ALS."
Diversity Of Expertise, But A Sharp Focus
Miller is a scientist at the Hope Center for Neurological Disorders. Its office and a few of its labs are housed in the BJC Institute of Health on Euclid, just east of Forest Park. But most of the center's 84 labs are scattered throughout 19 departments in the university's medical school complex. Despite the diversity of expertise and knowledge of these Hope scientists, all are working on two basic questions about neurological disorders -- what causes nerve cells to die and what can be done to protect them from degeneration. The BJC Institute is the hub where the university hopes to speed up breakthrough treatments for cancer, diabetes, infectious diseases common to women, certain membrane disorders and neurological disorders such as the one Miller has targeted.
The Hope Center itself grew out of the experience of Chris Hobler, who died of ALS at age 39 in 2005. A year earlier, he had founded ALS Hope, which evolved into Hope Happens. It, in turn, set up the Hope Center in collaboration with the Washington University Medical School. Among other things, Hope Happens helps to raise money to underwrite research by the center's 80 scientists, working with assistants in 80 separate labs. The center's funding includes a $10 million challenge grant from the Danforth Foundation.
While far-reaching, the progress Miller has made so far in finding a treatment for ALS is probably the equivalent of one bicycle tire making a single revolution during his five-mile trip to the office. But that's not to dismiss the value of his work; rather, it shows the dedication and determination a scientist must have to make breakthroughs.
"Science involve baby steps," says Anneliese Schaefer, deputy director of the Hope Center. "There might be very rare instances where somebody hits a ball out of the ball park, but the much more common way to get there is through small steps. They're the key. The first thing is to find one more step. It buys more time. If you can buy an extra year for somebody with some of those diseases, that's fantastic."
She says there's "real synergy here" because investigators approach their work from different angles but remain focused on the "common goal of the better understanding of shared mechanisms that underlie neurological disorders."
The Mouse Model And A New Model For Research
In the case of ALS, she says, the research has been helped because university scientists have developed a new mouse model more representative of people with the disease. Creation of the model, she says, is a good example of scientists "working from different approaches and very different mind-sets. It's not all people doing very similar things. They are all doing very different things, but they all are working toward a common end."
Research at the Hope Center, she says, is important because finding therapies and cures would save money since neurological disorders cost society $300 billion and 230,000 deaths each year.
"These are devastating diseases," Schaefer says. "Their impacts are huge. About 7,900 people a day are diagnosed with a neurological disorder. That's twice the number diagnosed with cancer."
The Hope Center defies all the stereotypes of the way science is done. Schaefer, who was a lawyer before earning a doctorate in science, admits to believing some stereotypes of scientists before she became a researcher. She used to think of the research scientist as having few conversations with others and spending the day peering into a microscope in a dimly lit room.
That image certainly doesn't fit the Hope model, which has plenty of open space and collaborative work by scientists who, she says, are constantly interacting with one another, discussing findings, sharing ideas and asking tough questions.
Clinical Trials On The Horizon
Miller, who describes the work as both fun but difficult, came to the center in 2007 from the University of California at San Diego. He believes his work with others will eventually lead to a breakthrough involving the mutation of the gene SOD1 having too much protein.
"An SOD1 with a mutation in it leads to ALS," he says. "This mistake is doing something bad. It's toxic. It's a problem, which led us to the idea that if you decrease the amount of protein that's there because of this mistake, we get less toxicity. It does damage to the motor neurons."
Even so, some of Miller's patients and others asked why lowering the protein level hadn't been done before. The reason is that no therapies have existed to address the issue up to this point.
His approach is to inject a chemical called antisense oligonucleotides into fluid surrounding the brain and spinal cord. In animal tests, the therapy worked and paved the way for testing the chemical in humans.
During the three clinical trials that will be conducted over the next few years, Miller and others will know the impact of the experiments on humans. SOD1-related ALS accounts for only 2 percent of all ALS, Miller acknowledges. The illnesses range from ALS to Alzheimer's, from Parkinson's to Huntington's. Like other Hope scientists, Miller believes that unlocking answers to one neurological disorder might open the doors to treatments, or even cures, for others.
"It's an important place for us to start with a new type of therapy that, in simple terms, goes in and erases the mistake," he said.
Funding for the Beacon's health reporting is provided in part by the Missouri Foundation for Health, a philanthropic organization that aims to improve the health of the people in the communities it serves.
