Tag Archives: APN-1607

A letter to Santa asking for a nice gift

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As I occasionally do, today I’ll create a blog post by combining a reader’s comment on a previous post with my reply.  This comment is from Jack Phillips, Chair of the Board of Directors of CurePSP: 

Larry, with the more rapidly progressing PSP-PF and its large % of PSP patients, it seems to put even more urgency on our Biomarker Acceleration Program. Do you believe the biomarker program will be able to distinguish between the different subtypes of PSP?
Jack

Hi, Jack,

Happy Holidays!

First, let’s assume that further research corroborates the existence, size, and statistical validity of the new subtype called PSP-PF, which isn’t a slam dunk.

You’re right that it would be great to have an accurate way to divide everyone with PSP into a) the two fastest-progressing types (PSP-RS and PSP-PF) and b) all the others.  But first, let’s see if that can be done clinically (i.e., using good old history and neuro exam).  Now that many of the people with the more aggressive variations of PSP-F and PSP-PI can be grouped as PSP-PF, the remaining, slower-progressing cases of PSP-F and PSP-PI would probably be easier to distinguish from PSP-RS than they were before, so maybe clinical would work well.

As for the ability of CurePSP’s pending biomarker program to do this job better than simple clinical evaluation: The first thing that comes to mind is to image the anatomical location(s) of the most intense tau deposition and/or inflammation in the brain.  Second-generation tau PET using the tracers 18F-PI-2620 or 18F-APN-1607 can already do those things to an extent.  That technique would now have to be refined and tested for its ability to identify PSP-PF. 

So, yes, a PET marker to diagnose PSP-PF (or maybe a PSP-PF/PSP-RS group) is a realistic goal in the next couple of years.  But the multi-million-dollar expense of all those experimental PET scans together with the administrative costs would be better handled by the companies making the PET ligands than by a relatively small nonprofit like CurePSP.   

As a more affordable alternative to PET, markers of neurodegeneration intensity might be able to distinguish PSP-RS/PSP-PF from the more slowly-progressing PSP types.  Measures of atrophy on ordinary MRI (conditioned on symptom duration at the time of the test) might be able to do this to an extent, as might serum levels of neurofilament light chain or inflammation-related compounds. 

Perhaps an index combining those two with clinical history and exam could be the ticket.  (Or perhaps all those tests would only succeed in identifying the same group of patients, in which case combining them would be pointless.  But that would be good to know.) Now, that’s something that the CurePSP Biomarker Initiative could afford to fund.

It’s awards season

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A caregiver has asked me, as CurePSP’s Chief Clinical Officer, to list the most important clinical research advances in PSP of 2023. Happy to oblige. Here are my top five in no particular order. 

  • The FDA approved a combination of two drugs called taurursodiol and sodium phenylbutyrate with the brand name “Relyvrio” for use in amyotrophic lateral sclerosis (ALS; Lou Gehrig disease).  A trial in PSP has already started to recruit patients.  The drugs address an issue in the mitochondria shared by the two diseases in different sets of neurons.
  • Tau PET ligand APN-1607 received go-ahead from the FDA to proceed to a pivotal Phase 3 trial.  Such a trial began recruitment in December in the US and will involve multiple other countries as well.  The compound would allow a diagnosis of PSP in early or equivocal cases by being taken up by the abnormal tau protein in the brain and imaged.
  • A drug called TPN-101 was found to be safe and well-tolerated in a Phase 1 trial of 30 patients with PSP.  The drug counters inflammation in the brain by reducing the transcription of ancient viral DNA in our genome.  Next is a small trial for efficacy.
  • A simple, remote, gait-monitoring system with only three sensors proved able to distinguish the gaits of PSP and PD.  Further testing for its ability to document progression or improvement will follow.
  • PET imaging of frontal lobe synapses showed good correlation with the PSP Rating Scale and with the results of cognitive testing.  This is different from typical PET in neurodegenerative disease, which images glucose utilization or protein aggregates.  The work suggests that synaptic imaging could be a good diagnostic marker in the earliest, pre-symptomatic stages of PSP.

But the most important piece of news is that several drug companies are planning to start clinical treatment trials in the next year or two. I’ll report on all that as it happens.