HAMMOCK LAB
The Laboratory of Pesticide Biotechnology
Alzheimer & Parkinson Disease
Alzheimer Disease (AD) & Parkinson Disease (PD) are distinct but related progressive neurodegenerative diseases, yielding debilitating disorders impacting both patients and loved ones. We previously showed in animal models of these diseases that sEH inhibition could reduce neuroinflammation and neurodegeneration.
Alzheimer Disease
Progress in understanding AD mechanism
Beside improving neuroinflammation and amyloid burden, we recently showed that sEH inhibition also improves cerebrovascular dysfunction resulting in improved cognition using a rat model of AD.
Progress in treating AD
In association with Harrington’s foundation, we are developing new sEH inhibitors that have good brain penetration to treat AD. Our preliminary pharmacokinetic studies revealed that these new sEH inhibitors showed better brain penetration. We are now starting to evaluate the efficacy of the new lead compounds in AD models. If successful, we can develop these compounds towards human clinical trials.
To support our Alzheimer’s and Parkinson’s Disease Research, donations are welcome: https://give.ucdavis.edu/IMED/HAMPARK.
Parkinson Disease
Progress in understanding PD mechanism
We found that sEH inhibition can reduce neuroinflammation and phosphorylation of α-synuclein, the main component of Lewy bodies, a pathological hallmark of PD. Therefore, sEH affects a process central to PD pathology; however, it was not clear how sEH affects α-synuclein structure.We recently observed that some natural sEH metabolites (diols) can directly interact with α-synuclein and promote oligomerization, a key step toward Lewy bodies formation. Using NMR HSQC, we determined how the diols interact with α-synuclein to change its structure. In addition, using a FRET-based biosensor system, we determined how sEH activity promotes α-synuclein aggregation in dopaminergic neurons.This finding provides a mechanistic understanding of the role of sEH in PD progression. This work will be published soon.
Progress in treating PD
Toward treating PD patients with sEH inhibitors, and in association with Eicosis LLC, a small company found by Dr. Hammock to bring sEH inhibitors from bench to bedside; UC Davis has just started a Clinical trial to determine the safety of the lead sEH inhibitor, EC5026, in PD patients. Detailed information about the clinical trial is available at: https://clinicaltrials.gov/study/NCT07142044?intr=EC5026&rank=1
