Gene therapy restores sense of smell, may aid research into other diseases caused by cilia defects
These are live olfactory sensory neurons, the cells responsible for detecting odors. Cells infected by a common cold virus (green) carrying cilia genes can now make cilia (red). Credit: University of Michigan Health System
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.
This is the surface of a healthy olfactory epithelium, the tissue in the nose involved in the sense of smell. Cilia project from olfactory sensory neurons and form a dense mat across the surface of the nasal cavity. Credit: University of Michigan Health SystemThe 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.
More information: Nature Medicine, Advance Online Publication, DOI 10.1038/nm.2860
Journal reference: Nature Medicine
Provided by University of Michigan Health System
- Scientists study cilia -- microscopic hair May 05, 2006 | not rated yet | 0
- Connecting cilia: Cellular antennae help cells stick together Apr 24, 2012 | not rated yet | 0
- Researchers identify new role for cilia protein in mitosis Apr 04, 2011 | not rated yet | 0
- Olfactory bulb size may change as sense of smell changes Jun 16, 2008 | not rated yet | 0
- How cells' sensing hairs are made Jun 08, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
Medical research 3 hours ago | 5 / 5 (1) | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research May 17, 2013 | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
2 hours ago | not rated yet | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
2 hours ago | not rated yet | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
7 hours ago | not rated yet | 0
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
3 hours ago | 5 / 5 (1) | 0 |
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
2 hours ago | not rated yet | 0
The devastating effect of Alzheimer's disease on bilingual people has been thrown into focus in Canada, where the sudden loss of a second language can leave sufferers feeling like strangers in their own country.
5 hours ago | not rated yet | 0