Research Briefs

Heartburn Meds Ineffective for Asthma?

For nearly 20 years, doctors blamed acid reflux, in part, for triggering severe asthma symptoms such as coughing, sneezing, and breathlessness. They often prescribed heartburn medication for asthma sufferers to help them with these symptoms.

A new national study, led in Illinois by a medical school researcher, has found that the longstanding practice of prescribing heartburn medication is ineffective and unnecessarily expensive for asthma patients who don’t exhibit symptoms associated with acid reflux such as heartburn or stomach pain.

“Now we know that we should not be using these medications for the treatment of asthma if the patient does not have reflux symptoms,” said Lewis Smith, MD, a professor of medicine and principal investigator of the Illinois Consortium for the American Lung Association’s Asthma Clinical Research Centers. Dr. Smith also is associate vice president for research at Northwestern University.

Asthma sufferers spend as much as $10 million annually on prescription heartburn medication because they believe it will help control attacks of wheezing, coughing, and breathlessness. About 23 million people in this country have asthma. An estimated 12 million individuals with asthma have an “attack” each year, and 2 million visit the emergency room.

The results of this study, published in the April 9 issue of the New England Journal of Medicine, are considered to be the most comprehensive evaluation to date of the efficacy of prescription heartburn medication to control respiratory flare-ups in asthmatics whose symptoms have not been well-controlled by other therapies.

Dr. Smith said the medication has been prescribed to asthma sufferers because “when you have a patient who is not doing well, you are always looking for ways that make sense to try to make them better. We should be trying these medications, but if the patient doesn’t get any better, we should stop them.”

On/Off Switch Determines Cell Fate

How does a human cell remember its past and decide its future? This is the six-million-dollar question that biomedical researchers have long sought to answer in their attempts to control cell fate and develop better cellular therapy.

Working with human bone marrow stem cells that can turn into bone or muscle, investigators at Children’s Memorial Research Center have demonstrated how these cells make decisions that determine their fate. William T. Tse, MD, PhD, assistant professor of pediatrics, and colleagues found that stem cells respond to environmental stimulation by dynamically balancing the production of bone- or muscle-forming factors.

Published in the April 21 issue of the Proceedings of the National Academy of Sciences, the research described the cells’ ability to control their fate with a “bistable switch” mechanism—similar to an on/off light switch. This mechanism explains important concepts in stem cell biology such as memory and plasticity. Further understanding these concepts may help researchers discover critical developmental genes that can be applied to cell fate control and cellular therapies.

Stem Cells Reverse MS, Diabetes

Autologous stem cell transplants can “reset” the immune systems of people with Type 1 diabetes or multiple sclerosis, according to research led by Northwestern’s Richard K. Burt, MD, associate professor of medicine.

His study published in the April 15 issue of the Journal of the American Medical Association showed that patients who underwent chemotherapy to destroy their immune systems and then received transplants of their own stem cells became insulin free—several of them for more than three years.

In Type 1 diabetes, the immune system attacks and ultimately destroys the insulin-secreting beta cells in the pancreas. After the transplant, patients showed an increased level of C-peptide, a byproduct of insulin production that indicates improved functioning of the beta cells.

The same approach appeared to reverse the neurological dysfunction of early-stage multiple sclerosis (MS). “This is the first time we have turned the tide on this disease,” said Dr. Burt, who is also chief of immunotherapy for autoimmune diseases at the medical school. He conducted the clinical trial at Northwestern Memorial Hospital.

Patients in the small phase I/II trial continued to improve for up to 24 months after the stem cell transplants, then stabilized. They experienced improvements in functioning affected by MS, including walking, ataxia, limb strength, vision, and incontinence. This study appeared in the March issue of The Lancet Neurology.

MS is an autoimmune disease in which the immune system attacks the central nervous system. In its early stages, the disease is characterized by intermittent neurological symptoms, called relapsing-remitting MS. During this time, individuals with the disease will either fully or partially recover from the symptoms experienced during the attacks.

New ALS Gene Discovery

Northwestern investigators in a collaborative study identified a new gene whose mutations cause 4 percent of inherited cases of ALS (amyotrophic lateral sclerosis). The study, reported in the February 27 issue of Science, points to a common cellular deficiency in the fatal neurological disorder, said Teepu Siddique, MD, Les Turner ALS Foundation/Herbert C. Wenske Foundation Professor in the Davee Department of Neurology and Clinical Neurological Sciences at the medical school. The new research is part of a national collaboration directed by Dr. Siddique, principal investigator for the “Genetics of ALS” project funded by the National Institutes of Health (NIH).

In earlier research Dr. Siddique and colleagues discovered the first and second ALS genes (the SOD1 gene in 1993 and the ALSIN gene in 2001) leading to familial, or inherited, ALS. They also identified ALS-related loci on chromosomes 9, 15, 16, and X.

The new study found mutations in the FUS/TLS gene in ALS families participating in the NIH-funded, multi-center project and included, among others, a large Italian family previously studied by Drs. Siddique and Pietro Cortelli of the University of Modena in Italy.

ALS causes the death of motor neurons in the central nervous system, which compromises the brain’s ability to send signals to the body’s muscles. This leads to loss of voluntary muscle movement, paralysis, and, eventually, death from respiratory failure. The cause of most cases of ALS is unknown.

“The purpose of this national study is to understand what causes the degeneration and death of motor neurons in order to find new cellular models of ALS, with the ultimate goal of advancing research that leads to a treatment,” explained Dr. Siddique. “Approximately 10 percent of ALS cases are inherited.”

The discovery of mutations in FUS/TLS shows a convergence of molecular pathway defects that damage motor neurons. FUS, like a previously identified familial ALS gene, TDP-43, is also a member of a class of proteins that bind RNA in neurons, according to Dr. Siddique.

The lead author on the Science paper was Robert H. Brown Jr., MD, of the University of Massachusetts, one of three institutions that collaborate with Dr. Siddique on the national study.

Presenting Smoothie Disease Fighters

Instead of a dreaded injection with a needle, someday getting vaccinated against disease may be as pleasant as drinking a yogurt smoothie.

A medical school scientist has developed a new oral vaccine using probiotics, the healthy bacteria found in dairy products like yogurt and cheese. He has successfully used the approach in a preclinical study to create immunity to anthrax exposure. Using the same method, he has also developed a breast cancer vaccine and vaccines for various infectious diseases.

This new generation vaccine has big benefits beyond eliminating the “Ouch!” factor. Delivering the vaccine to the gut—rather than injecting it into a muscle—harnesses the full power of the body’s primary immune force within the gut.

“This is potentially a great advance in the way we give vaccines to people,” said Mansour Mohamadzadeh, PhD, the lead author and an associate professor of medicine in gastroenterology at Northwestern. “You swallow the vaccine, and the bacteria colonize your intestine and start to produce the vaccine in your gut. Then it’s quickly dispatched throughout your body. If you can activate the immune system in your gut, you get a much more powerful immune response than by injecting it. The pathogenic bacteria will be eliminated faster.”

Most vaccines consist of protein and won’t maintain their effectiveness after being digested by the stomach. However, the lactobacillus protects the vaccine until it is in the small intestine.

The Northwestern study was reported in the March 17 issue of the Proceedings of the National Academy of Sciences.