A 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 tracer's movement throughout the brain.
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.
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 per cent 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.