Featured Research

from universities, journals, and other organizations

Researchers Successfully Deliver Drugs To The Primate Brainstem

Date:
October 3, 2002
Source:
NIH/National Institute Of Neurological Disorders And Stroke
Summary:
Current drug treatments of brainstem tumors are largely unsuccessful, because the drugs often fail to bypass the blood vessel lining protecting the brainstem. Now, an NIH study shows that researchers can effectively deliver drugs to the primate brainstem and monitor how the drugs spread inside the brain. The study provides hope for improving treatment of brainstem tumors and other brain diseases.

Current drug treatments of brainstem tumors are largely unsuccessful, because the drugs often fail to bypass the blood vessel lining protecting the brainstem. Now, an NIH study shows that researchers can effectively deliver drugs to the primate brainstem and monitor how the drugs spread inside the brain. The study provides hope for improving treatment of brainstem tumors and other brain diseases. In the new study, researchers at the National Institute of Neurological Disorders and Stroke (NINDS) used a technique called convection-enhanced delivery (CED), which was developed at the National Institutes of Health, to deliver a tracer molecule to the primate brainstem. They then used magnetic resonance imaging (MRI) to track the the tracer's movement throughout the brain. The study appears in the October 2002 issue of the Journal of Neurosurgery.

"It's difficult to safely treat the brainstem with available techniques because it's so intricate and complex, and because of the blood-brainstem barrier," says NINDS neurosurgeon and researcher Russell Lonser, M.D. "These findings suggest that we can reach the brainstem to treat diseases, and we can ensure that treatment is targeted to the critical region by monitoring it in real time." The blood-brainstem barrier is a type of lining in blood vessels that protects the brainstem against potentially harmful substances.

Co-author Edward H. Oldfield, M.D., chief of the Surgical Neurology Branch at NINDS, and colleagues developed CED in 1994. The technique uses small differences in pressure to make infused molecules flow through solid tissue. This enables large molecular weight molecules, such as those used in drugs, to penetrate the brainstem. Researchers have refined and expanded the uses of CED during the past 8 years, but until now, there has been no way to track precisely where the drugs were going and therefore no way to predict or prevent adverse side effects.

In the new study, Dr. Lonser and his colleagues first tested the safety of the tracer molecule, called Gd-albumin, by infusing it into the brainstems of rats. Gd-albumin molecules are similar in size to the molecules of most tumor-killing drugs. The rats showed no loss of function after 60 days, and tissue analyses showed only a normal amount of gliosis, or scar tissue, in the area immediately surrounding where the needle was inserted during the infusion.

The researchers then used a needle to target and deliver Gd-albumin into the pontine region (pons) of the brainstem in three healthy adult monkeys. Tumors in the pontine region are the most common type of brainstem tumor found in children. The animals were imaged in a magnetic resonance scanner during the infusion and 1, 2, 4, and 7 days after infusion.

The imaging studies showed a steady perfusion of the tracer through the brainstem with uniform concentrations throughout the perfused area. CED distributed amounts of the tracer that were comparable to the amount of drugs needed to treat brainstem diseases. Tests up to 35 days after infusion showed no neurological abnormalities, and the brainstem tissues appeared normal, except for a small amount of scar tissue near the site where the needle was inserted during the infusion, as was seen in the rodent model.

The brainstem consists of the midbrain, pons and medulla, structures located deep in the back of the brain. Tumors that arise in the brainstem are called brainstem gliomas and account for more than 10 percent of pediatric brain tumors. Since chemotherapy and other existing treatments for brainstem tumors are largely ineffective, more than 90 percent of children with these tumors die within 18 months of diagnosis, according to the National Cancer Institute. Brainstem tumors are less common in adults but account for more than two percent of adult brain tumors.

Drug delivery imaging with CED may ultimately be able to improve outcomes for children with brainstem gliomas, the researchers say. If it's proven safe and effective, the technique might also be used to treat other neurological diseases, such as Parkinson's disease, other tumors, epilepsy, and pain disorders. "This kind of imaging should provide novel treatment paradigms not only for brainstem gliomas, but also for other diseases for which treatment involves targeted delivery of therapeutic agents across the blood-brain barrier," says Dr. Lonser.

The researchers are currently testing several drugs for toxicity and effectiveness using CED and MRI in animal studies. "Once we show that these drugs can safely be given to animals in this manner and that they're effective, we can move on to human trials," says Dr. Lonser. "Right now, this method looks promising as a potential method for treating pediatric brainstem gliomas."

The research team also recently signed a Cooperative Research and Development Agreement (CRADA) with Kaleidos Pharma, Inc., of Seattle, Washington, to test CED and an experimental drug called TGF-alpha in an animal model of Parkinson's disease.

The NINDS is a component of the National Institutes of Health in Bethesda, Maryland, and is the nation's primary supporter of biomedical research on the brain and nervous system.

Reference:

Lonser RR, Walbridge S, Garmestani K, Butman JA, Walters H, Vortmeyer AO, Morrison PF, Brechbiel MW, Oldfield EH. "Successful and safe perfusion of the primate brainstem with a macromolecule: in vivo magnetic resonance imaging of macromolecular distribution during infusion." Journal of Neurosurgery, Vol. 97, No. 4, October 2002, pp. 905-913.


Story Source:

The above story is based on materials provided by NIH/National Institute Of Neurological Disorders And Stroke. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute Of Neurological Disorders And Stroke. "Researchers Successfully Deliver Drugs To The Primate Brainstem." ScienceDaily. ScienceDaily, 3 October 2002. <www.sciencedaily.com/releases/2002/10/021003075553.htm>.
NIH/National Institute Of Neurological Disorders And Stroke. (2002, October 3). Researchers Successfully Deliver Drugs To The Primate Brainstem. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2002/10/021003075553.htm
NIH/National Institute Of Neurological Disorders And Stroke. "Researchers Successfully Deliver Drugs To The Primate Brainstem." ScienceDaily. www.sciencedaily.com/releases/2002/10/021003075553.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins