Tag Archives: Alzheimer’s disease

We tauopathies have to stick together

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A post from two months ago explained why some positive results from a trial of an antisense oligonucleotide (ASO) drug for amyotrophic lateral sclerosis (ALS) is good news for PSP. Now, there’s similar but even better news about an ASO drug for Alzheimer’s disease called “diranersen.” Why better? Because unlike ALS, Alzheimer’s disease is a tau-based disorder, like PSP.

Quickie review: ASO drugs interfere with the action of messenger RNA, which is produced by a gene in the cell’s nucleus and carries it out to the ribosomes, where it’s translated into that gene’s specific protein. Trials of “neuroprotective” treatments hope to demonstrate a decline in the rate of worsening relative to placebo, affording the participant more time at each disease stage. Neuroprotective treatments like ASOs are not designed to produce improvement relative to the study’s baseline.

Yesterday (July 14, 2026) the results of a Phase 2 trial were released at the Alzheimer’s Association’s annual research conference in London. The double-blind design included 406 people with either “mild cognitive impairment” (MCI) or mild dementia caused by Alzheimer’s. (MCI does not include difficulties in performing daily activities and dementia does. For the purposes of the trial, MCI is defined as a score of 21-27 on the 30-point Mini-Mental Status Exam and dementia as 20 or less.) The participants were randomly assigned to one of three dosage levels or placebo for the 76 weeks of the double-blind period. The improvement was calculated as the difference between the first and last visit scores divided by the the first visit score.

The testing included five standard cognitive tests, tau levels in the spinal fluid, and positron emission tomography (PET) scans to image brain tau deposits. The drug, like all ASOs to date, is administered by injection into the spinal fluid space at the base of the spine, as for a spinal tap. Of those seven tests, the “primary outcome measure” was the Clinical Dementia Rating Sum of Boxes (CDR-SB), presumably because it’s the one with the most experience behind it.

Officially, the trial was negative because the CDR-SB failed to show a statistically significant slowing of the rate of worsening. But for two of the other four cognitive measures, there were statistically significant degrees of slowing of 50% in one and 42% in the other. The benefits shown by the PET and spinal fluid look equally impressive to my eyeballs, but their degree of statistical significance was not provided.

Transient pain in the head, limbs and/or back from the spinal taps were by far the most common side effects, occurring in about half of all participants, but no worse on diranersen than on placebo. The only side effect clearly worse on diranersen was a temporary confusional state (about 25% vs 5% on placbo). In all cases, it was gone within a week.

You can see and download the company’s detailed announcement here. Keep in mind that the drug company sponsor, Biogen, wrote it for public relations purposes. It is not sufficiently detailed for a research journal and has not been peer-reviewed, but Biogen has announced plans for an expensive Phase 3 trial, proving that they’re willing to put their money where their mouth is.

Biogen hasn’t parted with further details on the Phase 3, but if it starts in 2027 and is similar in design to the Phase 2 (but larger), one might expect results in 2030 and if all goes well, FDA approval shortly thereafter. Too long, I know, and besides, that’s Alzheimer’s — not PSP.

Of course, the elephant in the room is the trial of NIO-752, the ASO from Novartis, currently in a Phase 3 trial for PSP and stated for completion in mid-2029. The success to date of diranersen in Alzheimer’s, is excellent news for the prospects of a similar anti-tau ASO for PSP. As far as I know, there’s no clinically relevant difference between the two ASOs.

On behalf of the PSP community, I’ll thank Novartis for its efforts behind NIO-752 and encourage Biogen to extend its so-far-favorable Alzheimer’s program to PSP. Any other Pharma companies interested? The opportunity is ripe!

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Disclosure: In the past, I have consulted for both Novartis and Biogen, but have never had a financial interest in either company. The only possible exception is that Rutgers University, which owns the rights to the PSP Rating Scale because I was a professor there when I developed it, shares a fraction of its licensing fees with me.

ASOs: sci-fi takes a step closer to reality

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Great news from Biogen about an antisense oligonucleotide (ASO) designed to reduce production of the tau protein. 

First, some background: Most of you have heard about ASOs, but for a refresher, see these posts of mine from 2022 and 2026.  Here’s a slightly more technical but cutely animated explanation of ASOs from Harvard Medical School:

The elevator version is that an ASO is a short length of RNA that binds and inactivates the brain’s messenger RNA for a specific protein – or an abnormal version thereof – to prevent it from carrying the protein’s genetic code from the DNA to the protein-manufacturing machinery.  In theory, the production of any protein involved in the cause of a disease can be reduced by designing an appropriate ASO to bind to a segment of that protein’s messenger RNA.

The FDA has approved only one ASO so far – for a childhood muscle disorder called spinal muscular atrophy – but dozens of other ASOs are in the development pipeline for other conditions, including tauopathies. Biogen is currently testing its anti-tau ASO, called diranersen (formerly BIIB-080) against Alzheimer’s, by far the most common tauopathy.  A few days ago, they announced the results of a Phase 2 study of its safety and tolerability.  Here’s Biogen’s press release and here’s the description of the trial (without results) in clinicaltrials.gov. 

Diranersen was well-tolerated in people with Alzheimer’s, as expected based on the Phase 1 results.  The big news was that the rate of accumulation of abnormal tau protein aggregation actually did slow down, as measured by levels of tau in the spinal fluid and by positron emission tomographic (PET) images of the tau protein’s distribution in the brain. The press release didn’t say how much slowing occurred, but it was apparently enough to convince Biogen to proceed to a Phase 3 trial and to convince the FDA to let them do so. More details will be presented at the Alzheimer’s Association International Conference in London in July 2026.

The trial was not primarily designed to assess slowing of progression of the participants’ actual cognitive loss, but it gathered that information anyway in various forms.  The primary such test, called the “Clinical Dementia Rating Scale Sum of Boxes,” measures memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. It did not show a statistically significant slowing of progression for diranersen in Alzheimer’s, but the press release hints that there was some slight, statistically non-significant, degree of slowing.  

That’s all about Alzheimer’s. For PSP, a different company, Novartis, is testing a different anti-tau ASO (NIO-752).  It is also well tolerated, as demonstrated by a recently-completed Phase 1 trial.  If the brain’s accumulation of abnormal tau can be slowed down in Alzheimer’s disease, as the Biogen press release claims, then presumably PSP can achieve the same result.  Novartis says it’s still (as of May 15, 2026) analyzing its Phase 1 PSP efficacy results, but those would have to be spectacular to show statistical significance in so small a study.  That company will soon start testing NIO-752 in a Phase 2 PSP trial in the US and other countries, so keep an eye on clinicaltrials.gov for enrollment instructions.

Given these new results of one anti-tau ASO in one tauopathy, what are the prospects for a different anti-tau ASO in a different tauopathy?  I’ll duck the issue and call them promising but far from a slam dunk. That will be the topic of a future post, but what I can say right now is even these modest, preliminary signs of success with ASOs in tauopathies would have been science fiction back when I was in med school 50 years ago.