Breaking News
February 17, 2019 - MUSC researchers discover new mechanism for a class of anti-cancer drugs
February 17, 2019 - HPV misconceptions are causing women to miss smear tests
February 17, 2019 - Sanofi and Regeneron Offer Praluent (alirocumab) at a New Reduced U.S. List Price
February 17, 2019 - Researchers say auditory testing can identify children for autism screening
February 17, 2019 - New method analyzes how single biological cells react to stressful situations
February 17, 2019 - WVU gynecologic oncologist investigates novel treatment for cervical and vaginal cancers
February 17, 2019 - ADHD diagnoses poorly documented
February 17, 2019 - Majority of gender minority youth do not identify with traditional sexual identity labels
February 17, 2019 - AbbVie, Teneobio enter into strategic transaction to develop potential treatment for multiple myeloma
February 17, 2019 - Lower Birth Weight May Up Risk for Psychiatric Disorders
February 17, 2019 - Scientists identify reversible molecular defect underlying rheumatoid arthritis
February 17, 2019 - Moffitt researchers shed light on how CAR T cells function mechanistically
February 16, 2019 - Female Anatomy May Play Big Role in Sperm’s Success
February 16, 2019 - BMI may mediate inverse link between fiber intake, knee OA
February 16, 2019 - Movement impairments in autism can be reversed through behavioral training
February 16, 2019 - Studies address racial disparities in postpartum period and cardiovascular health
February 16, 2019 - Scientists implicate hidden genes in the severity of autism symptoms
February 16, 2019 - Decreased deep sleep linked to early signs of Alzheimer’s disease
February 16, 2019 - Neuroscientists show how the brain responds to texture
February 16, 2019 - Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
February 16, 2019 - What Can I Do About Sweating? (for Teens)
February 16, 2019 - Companies navigate dementia conversations with older workers
February 16, 2019 - Newly developed stem cell technologies show promise for treating PD patients
February 16, 2019 - Collaborative material research could advance self-assembling nanomaterials
February 16, 2019 - Researchers take major step in creating technology that mimics the human brain
February 16, 2019 - Erasing memories associated with cocaine use reduces drug seeking behavior
February 16, 2019 - Artificial intelligence can accurately predict prognosis of ovarian cancer patients
February 16, 2019 - Racial disparities in cancer deaths on the decline for America
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Children with ASD more likely to face maltreatment, study finds
February 16, 2019 - Study finds genetic vulnerability to use of menthol cigarettes
February 16, 2019 - H-RT should be the standard of care for men with low risk prostate cancer, study shows
February 16, 2019 - New technique using patients’ own modified cells could help treat Crohn’s disease
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
Nasal delivery of leptin hormone may help ease breathing problems during sleep

Nasal delivery of leptin hormone may help ease breathing problems during sleep

image_pdfDownload PDFimage_print

Experimenting with mice, Johns Hopkins Medicine researchers have added to evidence that a hormone best known for helping regulate hunger and body weight might also ease breathing problems experienced during sleep more effectively when given through the nose.

Although clinical trials using the hormone, known as leptin, aren’t yet on the horizon, the investigators say their success delivering it through the test animals’ noses may help them develop easier-to-use therapies for people with sleep-related breathing problems such as sleep apnea.

The findings were published online Oct. 12 in the American Journal of Respiratory and Critical Care Medicine.

Leptin, a hormone made by fat cells that was first identified in 1994, targets the brain’s appetite center, helping to regulate appetite. “Although leptin’s potential for treating obesity and curbing overeating failed to materialize in human trials, its role in the respiratory system has triggered new rounds of therapeutic possibilities,” says

A particular focus of his research is the search for new strategies to treat obstructive sleep apnea, a serious and even potentially lethal condition that affects approximately 30 percent of U.S. adults, Polotsky says. The prevalence increases to 50 percent among obese populations. The disorder is marked by frequent, brief periods when breathing stops during sleep due to upper airways closing. The result is oxygen deprivation. People with obesity are also at higher than usual risk of another sleep breathing problem called obesity hypoventilation syndrome, in which brain centers that regulate breathing during sleep operate abnormally and fail to increase breathing appropriately in response to carbon dioxide, which results in the buildup of carbon dioxide in the blood. The syndrome often accompanies sleep apnea.

Currently, the most common effective treatment for these sleep problems is regularly wearing a continuous positive airway pressure (CPAP) mask and machine, which mechanically increases air pressure in the throat to keep airways open during sleep. But because CPAP machines must be worn at all times during sleep and some patients find them cumbersome, uncomfortable, noisy and confining, substantial numbers of people cannot tolerate them and stop their use.

Polotsky says previous research has shown that leptin is essential in regulating breathing, and can successfully treat sleep-disordered breathing symptoms in obese mice lacking leptin. However, mice with diet-induced obesity are resistant to the leptin hormone and failed to respond when leptin was injected into the belly (or abdomen).

“One major reason for leptin-resistance is that it is hard for injected hormone to get through the blood-brain barrier and into the target brain cells,” says Slava Berger, a postdoctoral fellow in Polotsky’s lab and the first author of the paper. “We suspected that administering leptin through the nose might circumvent that barrier and overcome leptin-resistance in our test animals.”

To test that idea, the researchers first made adult male mice obese by feeding them a high-fat diet for 16 weeks. Since leptin can cause weight loss in the long term–which also reduces breathing problems –the researchers first assessed the immediate effect of a single dose of leptin (0.4 milligrams per kilogram of body weight) on sleep breathing before the weight-loss effect could take place. In both mice receiving leptin and those not receiving it?either squirted in the nose or injected in the belly?the researchers compared how much air mice inhaled, measured by changes in temperature, and the number of times mice experienced inadequate oxygen during sleep. They looked at blood oxygen levels by putting neck collars on mice, which were similar to the clips used on human fingers in urgent care settings to measure blood oxygen levels. The results indicated that only mice given leptin through the nose showed increased ventilation by over 40 percent during sleep, which alleviated upper airway obstruction and cut the number of times the mice had insufficient oxygen levels by more than half.

The researchers stained neurons from the brains of mice given leptin through the nose and found that the leptin receptor on the surface of the neurons had detected leptin, meaning this method of delivery bypassed the blood-brain barrier and transported leptin directly to the brain, thus avoiding leptin-resistance.

To further look at the longer term metabolic effects of leptin treatment, researchers treated a subset of their obese mice with leptin through the nose or the abdomen for two weeks. Again, only mice treated with leptin through the nose showed reduction in food intake and weight loss. Those mice lost 1 gram, almost 3 percent of total body weight, while the mice given leptin in the abdomen gained more than 3 grams, indicating leptin resistance.

“We believe our study provides the first evidence of its kind that giving leptin through the nose eases sleep disordered breathing,” says Polotsky. “In the future, we plan studies to look at the effects of different doses of leptin administered through the nose in mice.”

“Identifying key molecules that regulate breathing and how these molecules could be used to treat medical conditions such as sleep apnea is a significant achievement,” said Michael Twery, Ph.D., Director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. “The discovery sets the stage on which new treatment options can be developed.”

The researchers caution that, as was the case with leptin’s use to treat obesity, mouse studies may not be applicable to humans. “We believe that leptin treatment should be tested in humans at some point, but we first need to look into the potential side effects, allergic reactions and other factors before that can happen,” says Polotsky.

Costs, too, are a consideration for future therapies. According to the American Sleep Association, an average CPAP costs $500-$3,000. The current clinical use of leptin in the form of metreleptin–an extremely expensive synthetic replacement for leptin–treats rare cases of leptin deficiency at hundreds of thousands of dollars per year. However, Polotsky and Berger estimate that if nasal leptin is found safe and effective for clinical use, costs could be similar to inhaled forms of the hormone insulin, which runs about $25 per vial.

Source:

https://www.hopkinsmedicine.org/news/newsroom/news-releases/nasal-delivery-of-weight-loss-hormone-eases-breathing-problems-in-sleeping-mice

Tagged with:

About author

Related Articles