A unique drug designed to treat Alzheimer’s disease recently proved to be safe for human consumption in a critical phase of pharmaceutical research. The drug, PRI-002, was developed at Forschungszentrum Jülich in Germany, and was determined to be safe for human use after administering the drug daily for four weeks. This marked the completion of clinical Phase I, and the researchers’ next task will be to prove efficacy in Phase II.
Several candidates for Alzheimer’s pharmaceuticals make it through these first two phases but fail at clinical Phase III, in which efficacy and safety are confirmed. These drugs fell short because they showed no improvement in cognition and memory in those with Alzheimer’s. Many of these failed drugs targeted the amyloid beta protein (Abeta) formation, which is commonly associated with Alzheimer’s. PRI-002, however, goes about treating the disease in a completely different way.
About Abeta Monomers
“There is clear genetic evidence that Abeta plays a decisive role in the development of Alzheimer’s dementia,” says Prof. Dieter Willbold, Director of Jülich’s Structural Biochemistry Institute and of the Institute of Physical Biology at Heinrich Heine University Düsseldorf. He noted these drugs attempted to inhibit Abeta monomer formation by inhibiting certain enzymes, or that antibodies were used in attempts of targeting Abeta for degradation. These Abeta monomers are formed from the amyloid precursor protein (APP), and usually do not pose a threat. It is rare for these monomers to assemble into oligomers, but risk increases with age. Once an oligomer forms, it impairs nerve function in the brain, self-multiplies, and has mobility to damage various brain regions.
“We considered a different approach for our drug candidate, because the principle that it is not a question of the formation of Abeta itself but of its aggregation into oligomers, has been known for several years,” explained co-researcher Dr. Antje Willuweit from the Institute of Neuroscience and Medicine.
In contrast to these failed drugs that aimed to inhibit Abeta monomer formation, PRI-002 directly targets the oligomers without involving the immune system. By degrading these toxic oligomers into Abeta monomers, this novel drug could provide a new mechanism to target in treating Alzheimer’s.
PRI-002 is known as a D-peptide drug, which is a molecular mirror image (enantiomer) of the L-amino acid structures found in naturally occurring proteins. Though the molecular difference in structure is subtle, it allows these D-peptide drugs to be very difficult to degrade in the human body. This allows the D-peptides to be consumed orally without being digested how normal protein structures are.
“I have been watching the development of PRI-002 with great interest,” said says Prof. Oliver Peters from the Charité in Berlin. “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.”
Preclinical testing of PRI-002 involved orally administering the drug mouse models of Alzheimer’s disease, with results showing improved cognition and memory in the treated mice.
“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,” noted Dr. Janine Kutzsche, a researcher among Willbold’s team.
This successful Phase I in clinical trials showed that multiple, daily doses of PRI-002 were tolerated in healthy human participants, and the researchers hope to soon show the drug’s efficacy in clinical Phase II. These endeavors will likely be pursued through Priavoid, a company created by Forschungszentrum Jülich and Heinrich Heine University Düsseldorf scientists.
Alzheimer’s therapy passes another important test: Drug candidate PRI-002 has successfully completed Phase I of clinical research https://t.co/YrShhUZdRe
— dradaugo.com (@dradaugo) May 13, 2019
Sources: Forschungszentrum Jülich
