Promising new Alzheimer’s drug passes first phase of human trials

Scientists from Germany’s Jülich Research Centre are reporting successful results from the first phase of human clinical testing of a new Alzheimer’s drug. Following promising animal experiments the drug has initially now proved safe in human subjects and will soon move into Phase II clinical trials testing efficacy.

Called PRI-002, the new drug works by breaking down the toxic amyloid beta protein at the point it is aggregating into oligomer forms. While the larger amyloid aggregations, called plaques, are commonly associated with the progression of Alzheimer’s disease, the amyloid proteins can begin misfolding and clumping together years before any symptoms appear. These initial clusters of misfolding amyloid proteins are called oligomers, and some researchers suggest it is these oligomers that are the primary toxic element behind Alzheimer’s.

PRI-002 is different from many of the other recent failed Alzheimer’s drug candidates in that it doesn’t work by stimulating the immune system to attack amyloid plaques but instead directly breaks down the toxic amyloid oligomers. Early preclinical animal studies proved incredibly promising with the drug functioning not to prevent the onset of Alzheimer’s symptoms, but actually reverse cognitive decline in mice with fully developed pathological characteristics.

“We were able to show that mice with symptoms similar to Alzheimer’s had an improvement in cognitive performance after treatment with PRI-002,” says Janine Kutzsche, a scientist working on the preclinical studies. “The memory and cognition of the treated mice were significantly improved compared to the placebo group and could even no longer be distinguished from the memory performance of healthy mice.”

The next stage was to test the safety of the drug in healthy humans through single and multiple ascending dosages. The successful results from this Phase I safety trial have now been revealed, with scientists announcing no major adverse effects caused by the drug, even at the highest planned dosage.

“The drug concentrations in the blood reached the values that had previously been therapeutically effective in animal models,” says Dieter Willbold, one of the scientists working on the project. “Now we were also able to demonstrate the safety of the compound after four weeks of daily administration.”

At this point perhaps the only reasonable position to take on PRI-002 is one of cautious optimism. The field of Alzheimer’s research is littered with an unusually large volume of promising drugs that failed clinical trials at the final Phase III stage. So, while the drug is undeniably promising, there are still years of work ahead before it proves to be clinically useful.

“I have been watching the development of PRI-002 with great interest,” says Oliver Peters, an Alzheimer’s researcher not working on this particular project. “Not only because it represents an interesting and new approach in the therapy of Alzheimer’s disease, but also because it can be administered in tablet or capsule form, which is particularly advantageous for elderly people.”

The drug will now move into Phase II human clinical trials to evaluate its efficacy. These trials will inevitably take years to complete before it becomes clear whether the drug actually works in human patients, or whether PRI-002 will become yet another chapter in the ever-growing compendium of failed Alzheimer’s drugs.