3 May 2002 16:00 GMT

by Bea Perks, BioMedNet News

German neuroscientists have put neuropeptides up people's noses and discovered a revolutionary approach to delivering drugs straight to the brain. The approach could dramatically improve the range of therapies available to treat a variety of neurological disorders from obesity to memory loss, says Jan Born, professor of neuroepidemiology at the University of Lübeck.

Neuropeptides have been "completely neglected in all therapeutic approaches," Born told BioMedNet News today, and yet many brain diseases involve neuropeptide signaling.

After neurotransmitters, neuropeptides are the second major class of signal substances in the brain, he adds, but their large size has presented a "huge problem" to researchers hunting for ways of getting them across the blood-brain barrier.

Studies in animals have previously shown that compounds applied intranasally can enter the cerebrospinal fluid (CSF) directly, bypassing the circulation, but this has never been shown in humans.

Born and his team have now carried out trials in human subjects and shown that neuropeptides can indeed go straight from the nasal epithelium to the CSF without entering the circulation.

Neuropeptides complete the journey in minutes, which persuades Born that they diffuse through pores or clefts in the epithelium and end up in the CSF via an extracellular route, rather than taking an axonal pathway. The findings are published on Monday in Nature Neuroscience.

Born has wasted no time in setting up clinical trials with the new approach, whose results will be published soon.

Focusing on the neurological problem of weight regulation, he treated non-obese subjects with intranasal doses of the neuropeptide melanocortin. After six weeks of treatment the subjects weighed significantly less. The same study carried out on obese subjects gave disappointing results, however. "They didn't show any weight loss at all," sighed Born.

His team concludes that obese people develop resistance to the neuropeptidergic signals that regulate weight. So, he is starting a new trial in which obese subjects have to lose weight before starting the melanocortin treatment, in an effort to prolong weight loss.

Born's work with human subjects impresses Sveinbjorn Gizurarson, professor of biopharmacy at the University of Iceland in Reykjavik. Gizurarson has done similar studies in animals.

"This is the first clinical study I have seen in humans where you can demonstrate a flux from the nasal cavity into the cerebrospinal fluid," he told BioMedNet News today.

"The olfactory area is the only place in the whole human body where there is a direct contact between the outer surface and the central nervous system," he added.

Gizurarson says he is working with the US Food and Drug Administration to examine the risks associated with drugs that don't usually cross the blood-brain barrier. Born's work will have an impact on this, he says, and similar studies will need to be repeated to monitor safety parameters. Such factors did not form part of Born's studies.

"We have a lot of very good drugs, especially in cancer therapy, that need to be delivered into the brain," said Gizurarson. He has already shown that some of these can be absorbed across the nasal epithelium in animal models. Born's human studies, he says, point to clinical relevance.

"It is very encouraging for us that there is a proof of concept," he said.

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