Molecule restores cognition, memory in Alzheimer's disease model mice
UCLA researchers discovered DDL-920, a molecule that enhances cognitive functions in Alzheimer's model mice by increasing gamma oscillations, showing improved memory recall without side effects and potential for other neurological conditions.
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UCLA researchers have identified a molecule, DDL-920, that has shown promise in restoring cognitive functions in mice exhibiting symptoms of Alzheimer's disease. Unlike existing FDA-approved treatments that primarily focus on removing harmful brain plaques, DDL-920 aims to enhance the brain's memory circuitry by increasing gamma oscillations, which are crucial for cognitive processes. The study, published in the Proceedings of the National Academy of Sciences, involved administering DDL-920 to genetically modified mice over two weeks. The treated mice demonstrated improved memory recall in a maze test, performing similarly to healthy mice, without any adverse side effects. The researchers believe that if DDL-920 proves effective in humans, it could also have applications for other conditions associated with diminished gamma oscillations, such as depression and schizophrenia. The study's lead author, Dr. Istvan Mody, emphasized the novelty of this approach, which targets specific neurons to enhance cognitive function rather than merely addressing plaque accumulation.
- UCLA researchers developed DDL-920, a molecule that restores cognitive functions in Alzheimer's model mice.
- DDL-920 enhances gamma oscillations, crucial for memory, unlike current treatments that only remove brain plaques.
- Mice treated with DDL-920 showed improved memory recall without side effects.
- The compound may have potential applications for other neurological conditions like depression and schizophrenia.
- Further research is needed to assess the safety and efficacy of DDL-920 in humans.
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11 commentsIn this particular PNAS study you have to be hard-core reader and rummage around in the Methods section to uncover this awkward detail:
“Mouse strains used were C57BL/6J (Black 6, Jackson Laboratory; JAX stock #000664), JAX stock #003725 (Gabrd−/− mice on a C57BL/6J background…”
No wonder translation fails so often. It is not the mice, it is scientists cutting corners!
Some of us working with mice use many different genotypes of mice to ensure somewhat more robust results that have a better chance to generalize across mouse genomes and perhaps even human populations.
This is not new news. Here is a classic on this topic in Alzheimer’s research published in Neuron in 2019:
https://pubmed.ncbi.nlm.nih.gov/30595332/
One more point: There is a great deal of variation in expression of key genes/proteins mentions in this recent PNAS study, in particular parvalbumin and the GABA receptors.
For example parvalbumin protein levels in the hippocampus of different strains of mice at different ages vary over a 20-fold range. Here are the hard data from GeneNetwork.org;
https://genenetwork.org/show_trait?trait_id=61839_VFHILDKDKS...
And GABA receptors also have high levels of variation in hippocampus and other brain regions. Here is a good paper that compares mouse and human GABA receptor variation.
The obvious major caveat is that mice are not people, and that mouse models of what someone thinks are Alzheimer’s-like diseases are not people with Alzheimer’s.
Obviously the vast majority of treatments would be ineffective - and this in turn should let you design multi-treatment trials, where say a trial of 100 patients are used to test 50 substances, with each person receiving simultaneously tiny doses of ~25 candidate treatments.
Then the patient outcomes are used to identify which of the 50 likely have some effect, and a trial is done of just that substance.
I've recently learned about this and was surprised it's somewhat under the radar. Am I missing something?
Unfortunately mice disease models have not been showing efficacy in humans.
edit: ok apologies, after several attempts
http://www.chemspider.com/Chemical-Structure.24670873.html
3-(2-Naphthylmethyl)-4-(4-piperidinyl)-1H-pyrazol-1-ol
(incorrect stuff removed ...)
my fascination with cats just got even bigger :) One can wonder whether having a cat would prevent/slow the plagues accumulation to start with.
A SMALL molecule? And not formula? Odd.
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