Drug deliver system for brain cancer

October 23rd, 2008 - 12:49 pm ICT by IANS  

London, Oct 23 (IANS) Scientists have developed a new drug delivery system that breaches the blood-brain barrier to reach and kill cancer cells in the brain, according to the latest research. Following successful pre-clinical studies, the technology is being evaluated in two phase I clinical trials in patients with malignant glioma and brain metastases.

The blood-brain barrier is formed by a network of closely sealed endothelial cells in the brain’s capillaries, and it expresses a high level of proteins that pump foreign molecules away from the brain, while allowing molecules (glucose and insulin) essential for brain cells functioning.

This makes it very difficult for molecules, including anti-cancer drugs, to cross the blood-brain barrier and reach tumour cells in the brain. Currently, less than five percent of drugs (made up of very small molecules) are able to cross the barrier. One example is temozolomide, which is the only chemotherapy available for treating brain tumours.

In four related presentations, scientists from Canada, the US and France described how they are investigating a new drug delivery technology that provides a non-invasive and flexible way of transporting different drugs (for example, antibodies, proteins, peptides, siRNA, small molecules, etc.) across the blood-brain barrier and into the central nervous system.

The drug being evaluated in the four abstracts is called ANG1005. It is made up of one molecule of a peptide called Angiopep-2 joined together with three molecules of paclitaxel, a chemotherapy drug.

These trials are still being conducted, but, as of Sep 23, at least 22 patients with advanced solid tumours (including breast cancer, melanoma, liver cancer and 15 patients with brain metastases) have been treated with ANG1005 in the first trial.

The drug is given intravenously for an hour, every 21 days. At doses up to 500 mg the drug appears to be safe and well tolerated and no patient has discontinued due to adverse side-effects. The researchers are continuing to increase the dose.

Jean-Paul Castaigne, president and chief executive officer of Angiochem Inc, who presented the clinical trials results, said: “To date, the safety and tolerability of ANG1005 has been excellent in patients with advanced solid tumours and brain metastases.”

Reinhard Gabathuler is the author of one of the abstracts and chief scientific officer at Angiochem Inc (Montreal, Canada) - the company that is developing the Angiopep technology and ANG1005, according to a release of European Cancer Organisation.

He explained that “unlike invasive approaches to deliver drugs to the brain, Angiopep technology utilises the physiological approach by making use of the receptors on the surface of the blood-brain barrier that are responsible for actively transporting necessary molecules across the barrier to the brain.”

“The most interesting finding from this study is the potency of ANG1005 to bypass the blood-brain barrier and to allow paclitaxel into the brain where it shows anti-tumour activity,” said Francis Bichat, who heads the scientific platform at Oncodesign (Dijon, France).

These findings were presented at the 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva Wednesday.

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