Scientists Discover Urinary Biomarker That May Help Track ALS
A study in Neurology suggests that analyzing levels of the protein p75ECD in urine samples from people with amyotrophic lateral sclerosis (ALS) may help monitor disease progression as well as determine the effectiveness of therapies. The study was supported by NINDS and NCATS.
Dr. Mary-Louise Rogers, senior research fellow at Flinders University in Adelaide, Australia, and Dr. Michael Benatar, professor of neurology at the University of Miami, and their teams discovered that levels of urinary p75ECD increased gradually in patients with ALS as their disease progressed over a 2-year study period.
“It was encouraging to see changes in p75ECD over the course of the study, because it suggests an objective new method for tracking the progression of this aggressive disease,” said Dr. Amelie Gubitz, program director at NINDS. “In addition, it indicates the possibility of assessing whether levels of that protein decrease while patients try future treatments, to tell us whether the therapies are having any beneficial effects.”
Further analysis of the samples from 54 patients revealed that those who began the study with lower levels of urinary p75ECD survived longer than did patients who had higher levels of the protein initially, suggesting that it could be a prognostic marker of the disease and may inform patients about their illness. Benatar and his team noted that this may be useful in selecting participants for clinical trials and in improving study design.
ALS is a fatal neurodegenerative disease in which motor neurons—cells that control muscle activity such as walking, talking and breathing—gradually die off, resulting in paralysis. There is no cure for ALS.
Study Identifies African-Specific Genomic Variant Associated with Obesity
An international team of researchers has conducted the first study of its kind to look at the genomic underpinnings of obesity in continental Africans and African Americans. They discovered that approximately 1 percent of West Africans, African Americans and others of African ancestry carry a genomic variant that increases their risk of obesity, a finding that provides insight into why obesity clusters in families. Researchers at NHGRI and their African collaborators published their findings Mar. 13 in the journal Obesity.
People with genomic differences in the semaphorin-4D gene were about 6 pounds heavier than those without the genomic variant, according to the study. Most of the genomic studies conducted on obesity to date have been in people of European ancestry, despite an increased risk of obesity in people of African ancestry.
Obesity is a global health problem, contributing to premature death and morbidity by increasing a person’s risk of developing diabetes, hypertension, heart disease and some cancers. While obesity mostly results from lifestyle and cultural factors, including excess calorie intake and inadequate levels of physical activity, it has a strong genomic component.
The burden of obesity is, however, not the same across U.S. ethnic groups, with African Americans having the highest age-adjusted rates of obesity, said Dr. Charles Rotimi, chief of NHGRI’s Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch and director of the Center for Research on Genomics and Global Health at NIH.
“Eventually, we hope to learn how to better prevent or treat obesity,” Rotimi said.
NIH-Funded Study Helps Explain How Zebrafish Recover from Blinding Injuries
Researchers at Vanderbilt University have discovered that in zebrafish, decreased levels of the neurotransmitter gamma-aminobutyric acid (GABA) cue the retina, the light-sensing tissue in the back of the eye, to produce stem cells. The finding sheds light on how the zebrafish regenerates its retina after injury and informs efforts to restore vision in people who are blind. The research was funded by NEI and appeared online Mar. 9 in Stem Cell Reports.
“This work opens up new ideas for therapies for blinding diseases and has implications for the broader field of regenerative medicine,” said Dr. Tom Greenwell, NEI program officer for retinal neuroscience.
For years, vision scientists have studied zebrafish to understand their retinal regenerative capacity. Zebrafish easily recover from retinal injuries that would permanently blind a person. Early studies in zebrafish led to the idea that dying retinal cells release signals that trigger support cells in the retina called Muller glia to dedifferentiate—return to a stem-like state—and proliferate.
However, recent studies in the mouse brain and pancreas suggest GABA, a well-characterized neurotransmitter, might also play an important role in regeneration distinct from its role in communicating local signals from one neuron to the next. Scientists studying a part of the brain called the hippocampus found that GABA levels regulate the activity of neural stem cells. When GABA levels are high, the stem cells stay quiet, and if GABA levels decrease, then the stem cells start to divide, explained Dr. James Patton, Stevenson professor of biological sciences at Vanderbilt and senior author of the new study in zebrafish retina. A similar phenomenon was reported in mouse pancreas.
Based on these findings, Patton and his student Mahesh Rao hypothesized that GABA might be involved in the zebrafish retina’s regeneration response. To test their idea, Patton and Rao injected GABA inhibitors into undamaged zebrafish eyes and found that the fish developed a regenerative response; that is, Muller glia in the retina dedifferentiated and proliferated. Conversely, increasing GABA levels after inducing retinal damage suppressed proliferation of dedifferentiated Muller glia.
The findings supported the researchers’ hypothesis that decreased GABA signaling is a cue for regeneration in the zebrafish retina.
“This is the first report to show a regenerative role for GABA in the zebrafish retina,” said Patton.
Patton and co-authors are conducting ongoing work to determine if the dedifferentiated Muller glia can turn into functional retinal cells, such as the light-activated photoreceptors. They are also exploring whether altering GABA signaling might coax a regenerative response in the retina of other species such as mice.