The Week That Wasn't: CRISPR Prime, New Flu Drug, Calm Brain for Long Life

Donavyn Coffey


October 25, 2019

This week the internet was abuzz with tales of a CRISPR cure-all, a drug that knocks out the flu, and how calmer brains result in longer lives. Here's why you didn't read about them on Medscape.

CRISPR Cure-all

Biochemists at the Broad Institute published a paper in the journal Nature on what they call CRISPR prime, a new gene-editing tool they say is able to "correct 89% of known human pathogenic variants."

CRISPR prime, like the original CRISPR, uses the Cas9 enzyme to target a specific section of the genome. But once they reach the editing site, the old and the new diverge in their approach. The original CRISPR imposes a double-strand break to the DNA and then relies on the cell's own DNA repair mechanism to fix it. CRISPR prime has a pre-programmed reverse transcriptase enzyme fused to its Cas9. The researchers say this new method leaves less to chance because it carries the exact code of the desired edit, rather than relying on the cell's natural materials.

The researchers described how they used CRISPR prime to perform more than 175 edits in human cells including targeted insertions, deletions, and all 12 types of point mutation. They used the technique in experiments to correct the mutations responsible for both sickle-cell disease and Tay-Sachs disease. A new venture capitalist–backed company called Prime Labs purchased the rights to the new technology before the study's publication.

The findings generated a lot of hype, particularly about the researchers' claims that CRISPR prime could address about 89% of known disease-causing gene variants, but the work is far too exploratory to be applicable for Medscape readers who are treating patients with a genetic disease. Foremost, the experiments were conducted entirely in vitro, and as one researcher put it on Twitter, "EVERYTHING is harder when you move out of the dish." Researchers haven't yet worked out a way to deliver CRISPR prime to cells in the body as a therapy, and it's unknown how the immune system would respond to the enzymes. CRISPR prime may be able to address 89% of disease-causing mutations in principle, but that's different than curing or treating each disease.

Drug Knocks Out the Flu — In Ferrets

An experimental drug stopped the flu in its tracks when administered to ferrets within 12 hours of infection, researchers at the Georgia State University report in the journal Science Translational Medicine. When the ferrets (the most common animal model for flu studies) got the oral dose later, after developing a fever, the animals experienced reduced symptoms and a lower viral load compared with control animals and those that received oseltamivir (Tamiflu).

The ever-evolving nature of the influenza virus is a major public health obstacle, making one of the study's findings particularly intriguing: Influenza viruses grown in the drug's presence didn't develop resistance.

While the drug looks promising at this stage of development, it's still very early. This study can inform clinical trial design, but all of its findings in ferrets, including the drug's toxicity, bioavailability, and potency against the influenza virus, have to be studied in humans. A plain old flu shot is more help to patients, and relevant for clinicians, this flu season.

Calmer Brains, Longer Lives?

In a study recently published in Nature, researchers examined the brains of hundreds of deceased human subjects and found that those who lived longer showed lower brain excitation — more specifically, "a downregulation of genes related to neural excitation and synaptic function," they wrote.

To test the association, the researchers turned to nematodes. They found neural excitation increased with age, and that when they gave the nematodes a drug to slow neural excitation, they lived longer. When the researchers stimulated the nematodes' neurons, they died more quickly. The researchers also identified a protein called REST that was involved with neural excitation. Upregulating the REST protein decreased nematode neural excitation, increasing lifespan.

Neural excitation has also been linked to the beginnings of Alzheimer's disease, and the study authors suggest there may be potential to develop drugs targeting the mechanistic pathway they identified. Meditation may be an alternative way to decrease neural excitation, and has benefits Medscape has covered in the past. But as one of the paper's reviewers told STAT News, "It's too early to talk about manipulating the human lifespan based on this."  In other words, this study is not grounds for clinicians to begin prescribing regular yoga and meditation.

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