By Amy Dockser Marcus, Wall Street Journal Health Blog

It’s a well-known maxim in science that curing a disease in a rodent doesn’t guarantee the same results in a human being. But new research on using the drug cyclodextrin in mice is likely to help shape a clinical trial being planned for children with a rare and fatal genetic disease.

Scientists led by John M. Dietschy at the University of Texas Southwestern Medical School just published a paper in the Journal of Neuroscience on continuous cyclodextrin treatment for Niemann-Pick Type C, a fatal neurodegenerative condition in which cholesterol builds up in tissues and organs. The treatment not only kept mice alive but prevented the cognitive decline that is one of the hallmarks of the illness.

When delivered directly into each rodent’s central nervous system via the spinal column in order to better reach the brain, cyclodextrin “completely prevented the expected neurodegeneration,’’ the authors wrote.

The paper’s publication is especially propitious because the NIH announced earlier this year that it plans to start a clinical trial treating NPC patients with cyclodextrin, hopefully some time in 2012. One of the key issues still being discussed is whether to deliver the drug directly into the central nervous system (as was done with the mice in the paper) or through an infusion into a vein that carries the drug into the general circulatory system.

The new paper will fuel and shape that ongoing debate. It found that delivering cyclodextrin directly to the brain requires lower doses and appears to be more effective in reversing the cholesterol defect than infusions into a vein.

“It will be a very influential paper in the field,” scientist Daniel Ory tells the Health Blog. Ory ought to know: he is the principal investigator on an NIH grant focused on getting cyclodextrin from the lab into NPC patients. He’s also working closely with NIH’s Therapeutics for Rare and Neglected Diseases program, which selected NPC and cyclodextrin as one of its pilot projects to attempt to repurpose drugs for use in rare diseases.

Dietschy, who has published a number of previous papers on cyclodextrin and NPC, acknowledged that continuous, life-long administration of the drug into the central nervous system using a pump isn’t easy — even in a mouse. In children,  surgery is required to install, remove, and replace pumps, and the devices can become infected. Still, Dietschy says, if more data and studies back up the findings, he believes the technical obstacles can be overcome by surgeons.

Rumors about the paper’s findings were already creating a buzz among some in the NPC patient advocacy community even before it was published. In May, the National Niemann-Pick Disease Foundation, an advocacy group, sponsored a teleconference with Ory and NIH clinician Denny Porter to discuss the planned cyclodextrin trial.

In response to a question by a parent asking about the possibility of doing a trial using the delivery method described in the Dietschy paper, Porter said that there would be additional regulatory hurdles involved since it is a “huge jump in risk or risk-benefit ratio” to think about delivering the drug directly to the brain rather than through a vein.

Ory tells the Health Blog that investigators want the most efficient delivery method, but also one that can be rapidly moved into the clinic. He says the risks of injections into the spinal column, could potentially slow down the opening of a trial. Still, he agreed that the paper’s findings will inform the discussion.

One human experiment is already underway in twin girls with NPC, who have been receiving cyclodextrin infusions under the FDA’s compassionate use program.

Chris Hempel, the mother of the girls, Addison and Cassidy, tells the Health Blog they will submit a protocol for hospital approval to install a pump in each girl’s spine that will start delivering continuous cyclodextrin infusions to the brain.

Hempel says she closely follows Dietschy’s research, reading each paper. “As more research comes out, we can modify’’ the approach,” she says.

Dietschy says it’s too early to tell how or if the new results will be applied to patients. In the meantime, he says he plans to observe a colony of mice receiving continuous infusions to see how they progress. Researchers are still working on the technical issues but Dietschy says he can’t help but wonder: Will mice treated this way go on to live a normal life? And if so, could children?

Photo: Associated Press