Chondroitin 6-Sulphate Gene Therapy Restores Memory Function in Old Mice

The results reported here are intriguing, suggesting that some aspects of the extracellular matrix structure in the brain are of great importance to neural plasticity loss of memory function with age, at least in mice. This is quite novel. Most work on neurodegeneration touches only lightly, if at all, on the structure and composition of the extracellular matrix. Researchers here used a gene therapy to adjust the proportion of different chondroitin sulphates in matrix structures in old mice, and the resulting restoration of memory function is quite impressive.

Recent evidence has emerged of the role of perineuronal nets (PNNs) in neuroplasticity - the ability of the brain to learn and adapt - and to make memories. PNNs are cartilage-like structures that mostly surround inhibitory neurons in the brain. Their main function is to control the level of plasticity in the brain. They appear at around five years old in humans, and turn off the period of enhanced plasticity during which the connections in the brain are optimised. Then, plasticity is partially turned off, making the brain more efficient but less plastic.

PNNs contain compounds known as chondroitin sulphates. Some of these, such as chondroitin 4-sulphate, inhibit the action of the networks, inhibiting neuroplasticity; others, such as chondroitin 6-sulphate, promote neuroplasticity. As we age, the balance of these compounds changes, and as levels of chondroitin 6-sulphate decrease, so our ability to learn and form new memories changes, leading to age-related memory decline.

Researchers investigated whether manipulating the chondroitin sulphate composition of the PNNs might restore neuroplasticity and alleviate age-related memory deficits. To do this, the team looked at 20-month old mice - considered very old - and using a suite of tests showed that the mice exhibited deficits in their memory compared to six-month old mice. The team treated the ageing mice using a 'viral vector', a virus capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNs and found that this completely restored memory in the older mice, to a level similar to that seen in the younger mice.



This is a win for the SENS approach right? The stiffening of the extracellular matrix, and AGE's?

Though I think SENS has been working on an enzyme approach, here they are using gene therapy.... maybe they are one in the same though? We need to study the enzymes capable of breaking down AGE's, and then maybe gene therapy and a vector will be the delivery method.

Either way, this is pretty awesome news!

Posted by: GREGORY S SCHULTE at July 29th, 2021 11:18 AM

The team have already identified a potential drug, licensed for human use, that can be taken by mouth and inhibits the formation of PNNs. When this compound is given to mice and rats it can restore memory in ageing and also improves recovery in spinal cord injury. The researchers are investigating whether it might help alleviate memory loss in animal models of Alzheimer's disease.

Posted by: Jones at July 29th, 2021 1:07 PM

@Gregory S Schulte:
It's totally unrelated. It's not stiffening what is at play here.

Posted by: Antonio at July 29th, 2021 4:00 PM

@Antonio Ahhhhh my mistake, thanks for the info.

Posted by: GREGORY S SCHULTE at July 29th, 2021 5:51 PM

Have I mentioned that you guys (the people behind are awesome? Keep up the awesome work! Thank you!

Posted by: Matt at July 30th, 2021 10:50 AM

Another way to restore neuroplasticity may be to take hops flavonoids --

"The Prenylflavonoid ENDF1 Overrules Central Nervous System Growth Inhibitors and Facilitates Regeneration of DRG Neurons"

It would be interesting to know whether hops flavonoids promote formation of chondroitin 6-sulphate.

Posted by: L Pagnucco at July 30th, 2021 1:47 PM

Fwiw, shark cartilage is uniquely high in C6S( in proportion to C4S), and presumably other entourage molecules favoring a high C6S/C4S ratio. I ordered some capsules, I will aggressively dose it daily for a month. My expectations are low, but it is a cheap experiment.

Posted by: JohnD at August 4th, 2021 2:50 PM
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