Navigation Links
Nano-devices that cross blood-brain barrier open door to treatment of cerebral palsy

A team of scientists from Johns Hopkins and elsewhere have developed nano-devices that successfully cross the brain-blood barrier and deliver a drug that tames brain-damaging inflammation in rabbits with cerebral palsy.

A report on the experiments, conducted at Wayne State University in collaboration with the Perinatology Research Branch of the National Institute of Child Health and Human Development, before the lead and senior investigators moved to Johns Hopkins, is published in the April 18 issue of Science Translational Medicine.

For the study, researchers used tiny, manmade molecules laced with N-acetyl-L-cysteine (NAC), an anti-inflammatory drug used as antidote in acetaminophen poisoning. The researchers precision-targeted brain cells gone awry to halt brain injury. In doing so they improved the animals' neurologic function and motor skills.

The new approach holds therapeutic potential for a wide variety of neurologic disorders in humans that stem from neuro-inflammation, including Alzheimer's disease, stroke, autism and multiple sclerosis, the investigators say.

The scientists caution that the findings are a long way from human application, but that the simplicity and versatility of the drug-delivery system make it an ideal candidate for translation into clinical use.

"In crossing the blood-brain barrier and targeting the cells responsible for inflammation and brain injury, we believe we may have opened the door to new therapies for a wide-variety of neurologic disorders that stem from an inflammatory response gone haywire," says lead investigator Sujatha Kannan, M.D., now a pediatric critical-care specialist at Johns Hopkins Children's Center.

Cerebral palsy (CP), estimated to occur in three out of 1,000 newborns, is a lifelong, often devastating disorder caused by infection or reduced oxygen to the brain before, during or immediately after birth. Current therapies focus on assuaging symptoms and improving quality of life, but can neither reduce nor reverse neurologic damage and loss of motor function.

Neuro-inflammatory damage occurs when two types of brain cells called microglia and astrocytes normally deployed to protect the brain during infection and inflammation actually damage it by going into overdrive and destroying healthy brain cells along with damaged ones.

Directly treating cells in the brain has long proven difficult because of the biological and physiological systems that have evolved to protect the brain from blood-borne infections. The quest to deliver the drug to the brain also involved developing a technique to get past the brain-blood barrier, spare healthy brain cells and deliver the anti-inflammatory drug exclusively inside the rogue cells.

To do all this, the scientists used a globular, tree-like synthetic molecule, known as a dendrimer. Its size 2,000 times smaller than a red blood cell renders it fit for travel across the blood-brain barrier. Moreover, the dendrimer's tree-like structure allowed scientists to attach to it molecules of an anti-inflammatory NAC. The researchers tagged the drug-laced dendrimers with fluorescent tracers to monitor their journey to the brain and injected them into rabbits with cerebral palsy six hours after birth. Another group of newborn rabbits received an injection of NAC only.

Not only did the drug-loaded dendrimers make their way inside the brain but, once there, were rapidly swallowed by the overactive astrocytes and microglia.

"These rampant inflammatory cells, in effect, gobbled up their own poison," Kannan says.

"The dendrimers not only successfully crossed the blood-brain barrier but, perhaps more importantly, zeroed in on the very cells responsible for neuro-inflammation, releasing the therapeutic drug directly into them," says senior investigator Rangaramanujam Kannan, Ph.D., of the Center for Nanomedicine at the Johns Hopkins Wilmer Eye Institute.

Animals treated with dendrimer-borne NAC showed marked improvement in motor control and coordination within five days after birth, nearly reaching the motor skill of healthy rabbits. By comparison, rabbits treated with dendrimer-free NAC showed minimal, if any, improvement, even at doses 10 times higher than the dendrimer-borne version. Animals treated with the dendrimer-delivered drug also showed better muscle tone and less stiffness in the hind leg muscles, both hallmarks of CP.

Brain tissue analysis revealed that rabbits treated with dendrimer-borne NAC had notably fewer "bad" microglia the inflammatory cells responsible for brain damage as well as markedly lower levels of other inflammation markers. They also had better preserved myelin, the protein that sheaths nerves and is stripped or damaged in CP and other neurologic disorders. And even though CP is marked by neuron death in certain brain centers, animals who received dendrimer-borne NAC had higher number of neurons in the brain regions responsible for coordination and motor control, compared with untreated animals and those treated with NAC only.

The findings suggest that the treatment not only reduces inflammation in the cells, but may also prevent cell damage and cell death, the researchers said. The Kannans, who are married, say they plan to follow some treated animals into adulthood to ensure the improvements are not temporary.

A separate study, led by Rangaramanujam Kannan, has already demonstrated the therapeutic benefits of this approach in reversing retinal damage in rats with macular degeneration, the vision-robbing eye disorder that affects millions of older adults.


Contact: Ekaterina Pesheva
Johns Hopkins Medical Institutions

Related medicine news :

1. Independence Blue Cross teams with American College of Physicians to improve primary care
2. Care for Mentally Ill Vets at VA Centers May Differ Across U.S.
3. Project leads next decade of aging research across Europe
4. Project leads next decade of ageing research across Europe
5. After Stroke, Crossed Legs a Welcome Sign
6. Kids With ADHD Less Adept at Crossing the Street: Study
7. New hospital mortality rate index to be used across UK
8. 24th ECNP Congress: The most promising data from research across brain disorders
9. States vary in childrens health, gaps exist in insurance, quality care across sectors
10. Leading experts call for urgent action to avoid stroke crisis across Asia-Pacific region
11. Childrens doctors team up across state lines to fight disease
Post Your Comments:
(Date:12/1/2015)... ... December 01, 2015 , ... On Tuesday 27 Oct 2015, ... educate the personnel on spinal decompression therapy and offer his professional help. , ... The benefits come from creating negative intradiscal pressure which is conducive to retraction ...
(Date:12/1/2015)... ... 01, 2015 , ... World Patent Marketing , a vertically integrated ... allows for easier packing and organizing of items into one big, portable jar. , ... Cooper, CEO and Creative Director of World Patent Marketing and Desa Industries Inc ...
(Date:12/1/2015)... ME (PRWEB) , ... December 01, 2015 , ... Royal ... reports a new study that found post-menopausal women who took the nutritional supplement creatine, ... than women who trained but did not take creatine. , The report is part ...
(Date:12/1/2015)... ... December 01, 2015 , ... According to an article ... a discrimination claim against the U.S. Department of Health and Human Services, claiming that ... (ACA) plans are breaking the clause in the law prohibiting the denial of coverage ...
(Date:12/1/2015)... Los Angeles, CA (PRWEB) , ... December 01, 2015 , ... ... the United States, today announced that its iconic bottle has won top honors in ... drinks category. The Company also announced that it has been selected as a ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... and PITTSBURGH , Dec. ... announced that it expects to be the first to ... funded by international donors, TLE400 (Tenofovir Disoproxyl Fumarate 300 ... for $99 per patient, per year. Mylan partnered with ... The significantly reduced price could generate savings of tens ...
(Date:12/1/2015)...  Six months of adjunctive metformin therapy does not improve ... to new research from T1D Exchange and funded ... beneficial effect on measures of obesity, including weight and BMI. ... Journal of the American Medical Association , are from the ... on overweight and obese adolescents with type 1 diabetes. ...
(Date:12/1/2015)... 01, 2015 ... addition of the "2016 Europe ... E. Coli, Enterovirus, Rhinovirus, Rotavirus, Salmonella, ... their offering. --> ... the "2016 Europe Enteric Disease ...
Breaking Medicine Technology: