Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Can't smell anything? This discovery may give you hope

03.09.2012
Gene therapy in mice restores sense of smell, may also aid research into other diseases caused by cilia defects, U-M researchers say

Scientists have restored the sense of smell in mice through gene therapy for the first time -- a hopeful sign for people who can't smell anything from birth or lose it due to disease.

The achievement in curing congenital anosmia -- the medical term for lifelong inability to detect odors -- may also aid research on other conditions that also stem from problems with the cilia. Those tiny hair-shaped structures on the surfaces of cells throughout the body are involved in many diseases, from the kidneys to the eyes.

The new findings, published online in Nature Medicine, come from a team at the University of Michigan Medical School and their colleagues at several other institutions.

The researchers caution that it will take time for their work to affect human treatment, and that it will be most important for people who have lost their sense of smell due to a genetic disorder, rather than those who lose it due to aging, head trauma, or chronic sinus problems. But their work paves the way for a better understanding of anosmia at the cellular level.

"Using gene therapy in a mouse model of cilia dysfunction, we were able to rescue and restore olfactory function, or sense of smell," says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at U-M. "Essentially, we induced the neurons that transmit the sense of smell to regrow the cilia they'd lost."

The mice in the study all had a severe genetic defect that affected a protein called IFT88, causing a lack of cilia throughout their bodies. Such mice are prone to poor feeding and to early death as a result. In humans, the same genetic defect is fatal.

The researchers were able to insert normal IFT88 genes into the cells of the mice by giving them a common cold virus loaded with the normal DNA sequence, and allowing the virus to infect them and insert the DNA into the mouse's own cells. They then monitored cilia growth, feeding habits, and well as signals within and between the nerve cells, called neurons, that are involved in the sense of smell.

Only 14 days after the three-day treatment, the mice had a 60 percent increase in their body weight, an indication they were likely eating more. Cell-level indicators showed that neurons involved in smelling were firing correctly when the mice were exposed to amyl acetate, a strong-smelling chemical also called banana oil.

"At the molecular level, function that had been absent was restored," says Martens.

"By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants," says postdoctoral fellow and first author Jeremy McIntyre, Ph.D.

Martens notes that the research has importance for other ciliopathies, or diseases caused by cilia dysfunction. These include such conditions as polycystic kidney disease, retinitis pigmentosa in the eye, and rare inherited disorders such as Alström syndrome, Bardet-Biedl syndrome, primary ciliary dyskinesia and nephronopthisis.

Scientists believe that nearly every cell in the body has the capacity to grow one or more cilia. In the olfactory system, multiple cilia project from olfactory sensory neurons, sensory cells that are found in the olfactory epithelium, tissue high up in the nasal cavity. Receptors that bind odorants are localized on the cilia, which is why a loss of cilia results in a loss in the ability to smell.

Because the new findings show that gene therapy is a viable option for the functional rescue of cilia in established, already differentiated cells, researchers working on those conditions might be able to use gene therapy to attempt to restore cilia function as well.

Meanwhile, Martens and his team will continue to look for other cilia-related genetic causes of anosmia, including those that are not lethal in humans.

"We hope this stimulates the olfactory research community to look at anosmia caused by other factors, such as head trauma and degenerative diseases," he says. "We know a lot about how this system works – now have to look at how to fix it when it malfunctions." And, he notes because the neurons involved in the sense of smell connect to the nose, delivery of gene therapy treatments would not need to involve invasive procedures.

The study was funded by four parts of National Institutes of Health: the National Institute on Deafness and Other Communications Disorders, the National Institute on Diabetes and Digestive and Kidney Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Eye Institute.

In addition to Martens and McIntyre, the paper's authors include Ariell Joiner, Corey Williams, Paul Jenkins, Dyke McEwen, Lian Zhang and John Escobado from the Martens lab at U-M; Randall Reed from the Johns Hopkins University; Erica Davis, I-Chun Tsai and Nicholas Katsanis from Duke University; Aniko Sabo, Donna Muzny and Richard Gibbs from the Baylor College of Medcine; Eric Green and James Mullikin from the National Institutes of Health Intramural Sequencing Center; Bradley Yoder from the University of Alabama-Birmingham; Sophie Thomas and Tania Attié-Bitach from the Université Paris Descartes; Katarzyna Szymanska and Colin A Johnson from St. James's University Hospital in Leeds, UK; and Philip Beales from University College London, UK.

Reference: Nature Medicine, Advance Online Publication, DOI 10.1038/nm.2860

Grant numbers: R01DC009606, F32DC011990, R01DC004553, R01DC008295, R01DK75996, R01DK072301, R01DK075972, R01HD042601, and R01EY021872.

For more about the Martens lab at the U-M Medical School, visit http://www-personal.umich.edu/~martensj/Home.html

Kara Gavin | EurekAlert!
Further information:
http://www.umich.edu

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>