ALS: A new therapy from China?

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An article on SCMP tells about an observational clinical trial on six patients testing a new gene therapy: SNUG01.

It's about a genetic therapy proposed by a Chinese company: Sineugene.

This is not even a phase I clinical trial, what is known at the present state is that pre-clinical studies were promising (as usual) and it seems to have beneficial effects on one patient. If this is confirmed in larger trials, it would be a first: No ALS therapy has been able to reverse a bit of the disease. Please understand that the patient just slightly improved, it's not a cure.

Similar assertions have been made in the past by Western companies, sometimes going to the point of ridicule, like claiming patients were able again to do gym and motocross, even while the FDA rebuked the drug. I trust the FDA, not those companies. Yichang Jia, Ph.D. Yichang Jia, Ph.D., Co-founder of SineuGene

There are few scientific publications on this new therapy, here is what I understand: The underlying thesis of the scientists is that ALS (or FTD, PD and even Alzheimer(s disease) happens when there are both: * A genetic variant of some gene (which generates RNA-binding proteins (RBPs)) * A cellular stress (it could be a lot of things including insulin resistance) When those two conditions are met, stress granules which are normal phenomena are not processed correctly, instead in disease-susceptible neurons, stress induces mislocalization of mutant RBPs into stress granules and upregulation of ubiquitin, two hallmarks of disease pathology.

It's not known how SNUG01 (there are other names) works, here are some guesses: As the problem stems from the concomitance of two events, removing one of them could (partially?) solve the problem. We know that Relvyrio, TUDCA, and other drugs try to relieve cellular stress. But they are not very efficacious. One possibility as SNUG01 is a gene therapy, it that it tries to remedy the genetic variant. Hence the large therapeutic target that is announced.

I guess that it would be a knock-in therapy, contrary to the knock-out and ASO technologies that are favored by Western scientists. Or it could combine both: Deleting the wrong sequence and inserting a new correct one. Yet it is an AAV gene therapy so the payload can't be large, and a sophisticated gene therapy is unlikely.

AAV gene therapies have some problems and side effects, let's hope they are solved. One main problem is that there are millions of target cells to infect and trillions that should not be infected. Current gene therapies are unable to reach both goals.

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