Hope for treating currently-incurable neurodegenerative diseases?

What started more than a decade ago as a hunch among a small group of San Diego researchers has grown into real hope for treating currently-incurable neurodegenerative diseases.

Next year, Ionis Pharmaceuticals is expected to release clinical trial results for Huntington’s and Lou Gehrig’s (ALS) diseases that use designer DNA drugs to mute the mutant genes responsible for causing patients’ nervous systems to gradually go haywire.

If early trial results show a reduction in levels of the harmful proteins believed to cause these diseases, then larger trials are likely to follow providing a new path to fight life-stealing conditions that, for all of human history, have remained untouchable by medicine (like ataxia).

While positive results are far from certain, Ionis already has a serious proof-of-concept in Spinraza, a drug approved late last year that uses a similar but not identical approach to successfully treat a neurological condition that kills one in 1,000 children before they reach their second birthdays.

The big deal here is that Ionis has been able to show success working on the far side of the blood-brain barrier, a protective shield of sorts that automatically filters out most drugs injected into the bloodstream, making targets in the brain and spine extremely difficult to hit. The blood-brain barrier requires these drugs to be injected directly into the cerebrospinal fluid, and most thought such an approach would result in drugs simply floating around doing nothing.

So, if early-phase results, the first of which are expected in January, show that these DNA drugs — formally called “antisense oligonucleotides” — can reduce harmful proteins in nerve cells, well, that will be a very big deal indeed, especially because Spinraza has already proven that Ionis chemists have found ways to make these drugs last long enough in patients’ systems to create viable long-term treatments.

The key to early success in animals that has allowed further work in human patients has been the ability to prove that these drugs do get sucked in by nerve cells and that chemical wizardry performed in Ionis’s huge labs has made the drug stable and durable enough to last long enough to bond with passing mRNA strands.

The efficacy has amazed everyone. We don’t get two hours of efficacy. We don’t get two to three days. We don’t get two or three weeks. We get three or four months. The drug lasts a really long time. That means that patients could theoretically come in a few times a year, get a shot in the spine, and go home.

So, are similar results coming for Huntington’s and ALS given that they use the same designer DNA approach in a different way?

At the moment, all results are still blinded, and researchers don’t know what’s coming.
26 November 2017

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