The future of disease diagnosis may lie in
a breathalyzer-like technology currently under development at the University of
Wisconsin-Madison.
New research published online in Metabolism demonstrates a simple but
sensitive method that can distinguish normal and disease-state glucose
metabolism by a quick assay of blood or exhaled air.
Many diseases, including diabetes, cancer,
and infections, alter the body’s metabolism in distinctive ways. The new work
shows that these biochemical changes can be detected much sooner than typical
symptoms would appear—even within a few hours—offering hope of early disease
detection and diagnosis.
“With this methodology, we have
advanced methods for tracing metabolic pathways that are perturbed in
disease,” says senior author Fariba Assadi-Porter, a UW-Madison biochemist and scientist at the Nuclear Magnetic Resonance
Facility at Madison.
“It’s a cheaper, faster, and more sensitive method of diagnosis.”
The researchers studied mice with metabolic
symptoms similar to those seen in women with polycystic ovary syndrome (PCOS),
an endocrine disorder that can cause a wide range of symptoms including
infertility, ovarian cysts, and metabolic dysfunction. PCOS affects
approximately one in 10 women but currently can only be diagnosed after puberty
and by exclusion of all other likely diseases—a time-consuming and frustrating
process for patients and doctors alike.
“The goal is to find a better way of
diagnosing these women early on, before puberty, when the disease can be
controlled by medication or exercise and diet, and to prevent these women from
getting metabolic syndromes like diabetes, obesity, and associated problems
like heart disease,” Assadi-Porter says.
The researchers were able to detect
distinct metabolic changes in the mice by measuring the isotopic signatures of
carbon-containing metabolic byproducts in the blood or breath. They injected
glucose containing a single atom of the heavier isotope carbon-13 to trace
which metabolic pathways were most active in the sick or healthy mice. Within
minutes, they could measure changes in the ratio of carbon-12 to carbon-13 in
the carbon dioxide exhaled by the mice, says co-author Warren Porter, a UW-Madison professor of zoology.
One advantage of the approach is that it
surveys the workings of the entire body with a single measure. In addition to
simplifying diagnosis, it could also provide rapid feedback about the
effectiveness of treatments.
“The pattern of these ratios in blood
or breath is different for different diseases—for example cancer, diabetes, or
obesity—which makes this applicable to a wide range of diseases,” explains
Assadi-Porter.
The technology relies on the fact that the
body uses different sources to produce energy under different conditions.
“Your body changes its fuel source. When we’re healthy we use the food
that we eat,” Porter says. “When we get sick, the immune system takes
over the body and starts tearing apart proteins to make antibodies and use them
as an energy source.”
That shift from sugars to proteins engages
different biochemical pathways in the body, resulting in distinct changes in
the carbon isotopes that show up in exhaled carbon dioxide. If detected
quickly, these changes may signal the earliest stages of disease.
The researchers found similar patterns
using two independent assays—nuclear magnetic resonance spectroscopy on blood
serum and cavity ring-down spectroscopy on exhaled breath. The breath-based
method is particularly exciting, they say, because it is non-invasive and even
more sensitive than the blood-based assays.
In the mice, the techniques were sensitive
enough to detect statistically significant differences between even very small
populations of healthy and sick mice.
The current cavity ring-down spectroscopy
analysis uses a machine about the size of a shoebox, but the researchers
envision a small, handheld breathalyzer that could easily be taken into rural
or remote areas. They co-founded a company, Isomark LLC, to develop the
technology and its applications. They hope to explore the underlying biology of
disease and better understand whether the distinctive biochemical changes they
can observe are causative or side effects.
