"Zinc finger" gene therapy tackles the toxic tangles of Alzheimer's

"Zinc finger" gene therapy tac...
An artist's depiction of amyloid plaques surrounded by tau tangles, both considered key pathological signs of Alzheimer's disease
An artist's depiction of amyloid plaques surrounded by tau tangles, both considered key pathological signs of Alzheimer's disease
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An artist's depiction of amyloid plaques surrounded by tau tangles, both considered key pathological signs of Alzheimer's disease
An artist's depiction of amyloid plaques surrounded by tau tangles, both considered key pathological signs of Alzheimer's disease

There are a lot of unknowns when it comes to the way Alzheimer's takes hold in the brain, but one area where researchers are focusing much of their attention is the development of toxic clumps of proteins in the brain. These harmful clusters are seen as key players in the cognitive decline associated with the disease, and scientists have now found that a single injection of a novel gene therapy may be able to prevent a significant portion of them from forming.

The abnormal accumulation of tau and amyloid proteins are seen as key pathological signs of Alzheimer's disease, and have therefore provided a target for scientists working to both detect the disease more effectively and come up with new ways to treat it. Recent breakthroughs have demonstrated how earlier diagnosis could be achieved through brain imaging technologies or blood tests, and we've also seen how next-gen compounds and implants could prevent these harmful clumps from developing in the first place.

This new research, carried out by scientists at the Massachusetts General Hospital, explores how these biomarkers might be targeted via gene therapy. Last year we looked at an interesting example of this, where researchers were able to introduce genetic material to activate an enzyme that improved memory in mice with advanced Alzheimer's.

The new study takes a different route, taking aim at tau proteins that can misfold and clump together to form harmful neurofibrillary tangles. The gene therapy uses proteins known as zinc finger protein transcription factors, which can be used to alter the expression of certain genes, in this case working to silence the gene expression that codes for tau. Mice with Alzheimer's were given a single injection of this "zinc finger" gene therapy, either directly into the hippocampus of the brain or into a blood vessel intravenously.

This one-off treatment brought about huge reductions in tau proteins, reducing their levels in the brain by between 50 to 80 percent, even as long as 11 months after that single dose. In addition to this substantial lowering of tau levels, the researchers found the therapy also repaired some of the neuronal damage around amyloid plaques in the brains of the diseased rodents.

“The technology worked just the way we had hoped – reducing tau substantially for as long as we looked, causing no side effects that we could see even over many, many months, and improving the pathological changes in the brains of the animals,” says senior author Bradley Hyman. “This suggests a plan forward to try to help patients.”

While the research was carried out on rodents and its effectiveness on human Alzheimer's patients remains unknown, these early results are certainly promising. Working in favor of the technique is its simplicity, conferring such long-lasting and persistent improvements even after only a single injection.

“This was the result of a single treatment of gene regulation therapy, which could be given by an injection into the bloodstream,” says Hyman. “While this therapy is far from patients – as much more development and safety testing would need to be done – it is a promising and exciting first step.”

The research was published in the journal Science Advances.

Source: Massachusetts General Hospital

Why the, “far from patients” comment from the researcher?
There are pre-existing protocols for using experimental or early stage drug treatments on people with life threatening diseases for whom every conceivable alternative has proved fruitless.
Why not try something like this in very advanced and otherwise hopeless cases of Alzheimer’s, or would that be too late for this type of therapy?
Robt: Agree completely,especially in cases of advanced cancer. Dementia is just as deadly,so why indeed not try these potential therapies in people who can still sign off on them? I would be willing to absolve the hospital/researchers of any legal liability if there were any chance something like this could help.
Nice Nick, this article is not in my normal medical feed. Interesting and hope it develops therapeutically.

Robt & Michael: Why 'far from patients' from any ethical researcher? This is a report of a "Proof of Concept" therapy. On page 4/19 in the downloadable pdf they state very clearly the toxicity they were skirting: "could lead to unintended neuroinflammation, neurotoxicity, and axonal or synaptic alterations. "

With students I've always asked them - would you treat your grandparents in this manner? Use this drug? Put them through all you see ongoing for these patients? If their answer is no, it opens the morality of excessive care versus the ethics of allowing nature to take its course when there are slim avenues to improvement or extending of life.

When it is proven to perform repeatedly without destroying neurological tissues or causing inflammation - or even autoimmune triggering - then it becomes a moral and ethical decision for providers to address with their patients. To do otherwise is to revisit that whole bone-marrow transplant as cure for advanced breast cancer and requiring insurance companies to pay for the treatment - only to find the therapy was not much better than ignoring the cancer progression.