Emory cell biologist David Katz’s lab has facilitated a collaboration with our neighbors at Oglethorpe University, working with undergraduates on the worm C. elegans and contributing to Alzheimer’s/frontotemporal dementia research. A new article from Oglethorpe describes how C. elegans is ideal for undergraduate biology instruction. Check it out.
In the photo: Oglethorpe student and Katz lab intern Caitlin May, Oglethorpe biology professor Karen Schmeichel, Elias Castro — also an Oglethorpe student and Katz lab intern, Katz lab postdoc Teresa Lee and David Katz.
Last week, Lab Land noticed similarities between two independent lines of research from the Escayg and Traynelis/Yuan labs at Emory. Both were published recently and deal with rare forms of genetic epilepsy, in which molecular understanding of the cause leads to individualized treatment, albeit with limited benefit.
Both conditions are linked to an excess of neuronal excitation, and both can be addressed using medications that have also been tested for Alzheimer’s. A critical difference is that memantine is FDA-approved for Alzheimer’s, but huperzine A is not.
|What gene is mutated?
||SCN1A – sodium ion channel
||GRIN2A – NMDA receptor subunit
|What is the beneficial drug?
|How does the drug work?
||NMDA receptor antagonist
|Other drugs that use the same mechanism
||Alzheimer’s medications such as donepezil
Irreversible + stronger: insecticides, nerve gas
|Ketamine, phencyclidine (aka PCP)
Our recent news item on Emory pathologist Keqiang Ye’s obesity-related researchÂ (Molecule from trees helps female mice only resist weight gain) understatesÂ how many disease models the proto-drugÂ he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in.Â We doÂ mentionÂ that Ye’s partners in Australia and Shanghai are applying to begin phase IÂ clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.
Ye’sÂ 2010 PNAS paper covered models of Parkinson’s, stroke and seizure. Later publications take on animal models of depression, Alzheimer’s, fear learning, hearing lossÂ andÂ peripheral nerve injury. AlthoughÂ those findingsÂ begin to sound too good to be true, outside laboratories have been confirming the results (not 100 percent positive, but nothing’s perfect).Â Â Plenty of drugs don’tÂ make itÂ from animal models into the clinic, but this is a solid body of work so far.
Alzheimer’s protein pathology
While a wise Dane once proposed that predictions are dangerous, especially concerningÂ the future, it’s usuallyÂ helpful to plan ahead. Here are five biomedical research topicsÂ we think will occupy our attention in 2015.
1. Alzheimer’s Weâ€™re hearing discordant music coming from Alzheimerâ€™s researchers. Large pharmaceutical companies are shutting down clinical trials in frustration, but researchers keep coming forward with biomarkers that mightÂ predict future disease. This confusing situation calls for some new thinking. Allan Levey, Jim Lah and colleagues have been preparing the way for a â€œbeyond the usual suspectsâ€ look at Alzheimerâ€™s disease. We are looking forward to Leveyâ€™s appearance at the 2015 AAAS meeting and to drug discovery wizard Keqiang Yeâ€™s continuing work on new therapeutic targets.
2. Ebola While the scare over Ebola in the United States may be over (we hope so!), the outbreak continues to devastate countriesÂ in West Africa. Clinical trials testingÂ vaccines and experimental drugs are underway or will be soon. Read more
Developing drugs that can change the progression of Alzheimer’s disease is a huge challenge. In the last few years, more than one pharmaceutical firm have abandoned clinical programs in Alzheimer’s that once looked promising. Still, Emory and Scripps scientists have found an approach that deserves a second look and more investigation.
One straightforward drug strategy against Alzheimerâ€™s is to turn down the brainâ€™s production of beta-amyloid, the key component of the diseaseâ€™s characteristic plaques. A toxic fragment of a protein found in healthy brains, beta-amyloid accumulates in the brains of people affected by the disease.
The enzyme that determines how much beta-amyloid brain cells generate is called BACE (beta-secretase or beta-site APP cleaving enzyme). Yet finding drugs that inhibit that elusive enzyme has been far from straightforward.
Now researchersÂ have identified a way to shut down production of beta-amyloid by diverting BACE to a different part of the cell and inhibiting its activity. The results were published this week in Journal of Neuroscience. Read more