On the heels of a June 17 paper showing a small molecule's ability to declutter pathological protein buildups in the brain, researchers from the University of California, San Diego (UCSD) and the University of Pennsylvania have received a $6.9 million grant from the National Institute on Aging to prepare the drug for clinical trials.
The drug, CNDR-51997, helps stabilize the connections between the Alzheimer’s-associated protein tau and microtubules, key structural components of nerve cells. Tau is also implicated in other neurodegenerative diseases, but, with no approved therapies targeting it, the protein remains a white whale for biotech.
"This compound has been designed to combat tau-mediated neurodegeneration and our preclinical data suggest that it could be beneficial for the treatment of Alzheimer's and related dementias,” molecular biologist and UCSD grant recipient Carlo Ballatore, Ph.D., said in an Aug. 20 release.
The grant will provide three years of funding for the researchers to conduct safety studies of the drug, in preparation for submitting an Investigational New Drug application to the FDA and moving into phase 1 human trials.
In the June study, published in the journal Alzheimer’s & Dementia, CNDR-51997 prevented tau from becoming detached from microtubules in mice, a feature of Alzheimer’s and other neurodegenerative diseases. This reduced the buildup of tau and the other primary Alzheimer’s-associated protein, amyloid beta.
“The potential of CNDR-51997 to address tau-related diseases beyond Alzheimer's is another important aspect of its therapeutic promise,” biochemist and Penn grant recipient Kurt Brunden, Ph.D., said in the release.
There are currently no approved drugs that target tau, but other efforts to address the problematic protein are underway. Denali Therapeutics recently published data on a technique to get antisense oligonucleotides, which can target the gene that codes for tau, across the blood-brain barrier. And, at the Alzheimer’s Association International Conference at the end of July, AC Immune presented preclinical data of its own brain-penetrating small molecules that can disrupt misfolded bundles of tau.
Earlier this month, Eli Lilly's tau-focused drug, an inhibitor of the O-GlcNAcase enzyme called LY3372689, failed to reach its primary endpoint of reducing disease severity in a phase 2 Alzheimer’s trial.