Today reader RW posted a comment asking about the status of the NIO752 trial. I thought my answer was so, SO well-crafted and informative that I just had to promote it from a comment response to a full blog post, and here it is:
RW:
First, for the benefit of your fellow readers, NIO752 is the anti-sense oligonucleotide from Novartis. An ASO is a short span of RNA injected into the spinal fluid space. In this case, the injections are given four times: every three months for a year. The drug reduces production of tau at its source — where its gene is transcribed into protein. In my opinion, it’s more likely to work against PSP than any other past or current experimental drug. However, the need for the spinal injections could limit its appeal, especially if one or more of the oral (i.e., more convenient) drugs currently in more advanced stages of clinical testing reach the market first.
The Phase 1 NIO752 trial ended a month or so ago and Novartis, apparently, is still crunching the numbers. It’s typical for that to take 2 or 3 months, so I wouldn’t infer anything from it. Keep in mind that this was only a Phase 1 trial, powered to assess safety, not efficacy. I haven’t heard anything through the grapevine about major safety problems during the trial, but you never know what the actual data might show or how the company might react in terms of continuing to advance the drug into a Phase 2 trial.
LG
PSP Blog 
https://journals.lww.com/nrronline/fulltext/2025/03000/antisense_oligonucleotides_provide_optimism_to_the.19.aspx
Thank you very much, Dr. Golbe. I may be reading too much into what you are saying, but is there a possibility, do you think, that one of the orally administered antisense oligonucleotides from a company other than Novartis might be directed to treat PSP? I remember Biogen, for one, reporting positive initial results based on testing of their ASO for Alzheimer’s disease. Or maybe you are saying that once an ASO gains FDA approval for another disease, the path to repurpose it toward treating PSP would be relatively shorter/smoother?
All the best.
Maura
M: There are a few ways to make an ASO possible to administer by mouth and some are being tested in neurodegenerative diseases, but not so far in PSP. I’m far from an expert in ASOs, but I’d think that pretty much any ASO modification that allows it to be given orally would work on any ASO. However, because the mRNA target of the ASO is different for each disease, an ASO effective in one disease would probably be useless in another. Even across the various tauopathies, there are enough differences in the tau that an ASO that works for one may not work for another. Also, keep in mind that an ASO for Alzheimer’s might be directed at the gene encoding beta-amyloid, rather than the MAPT gene, which encodes tau. LG
IT WORKS! My husband was in the trial. No cure but a great year – his condition was improved in so many ways. I have been waiting for someone at Cure PSP to put out the word. I assumed they were going to present at the Montreal conference but they did not.
We are so sad they refuse to continue to give it to us. Novartis has a published policy to keep giving people in a trial drugs that provide help but denied us with the excuse it was phase 1. Even if it is too expensive when administered through the spine it provides evidence that this horrible disease can be managed and greatly improves life. We would love to go to Novartis and show them how it works. Hopefully they are not just proceeding on using it for Alzheimers. We have been watching and waiting to see if they release results. They need to publish them. HOPE MATTERS! Kathy and Steve from San Diego, California.
KB: I replied to your excellent questions in the form of today’s post. LG