A welcome formality

I see my patients with PSP on special clinic days when I have arranged for specialized professional help and have allotted extra time for the visits. The downside is that that it can be a dispiriting few hours, with little to offer anyone that day beyond symptomatic treatment, information and a pep talk. So I use this blog to accentuate the positive.

In that vein, I’m happy to report the drug/biotech industry’s efforts to develop a therapeutic antibody are proceeding apace. The latest tidbit is that the FDA has granted orphan drug status to the anti-tau antibody designated C2N-8E12 being developed by a joint venture of C2N Diagnostics and Abbvie. A 32-patient Phase I trial headed by Adam Boxer at UCSF will begin sometime soon. Achieving orphan status allows the company certain financial advantages and a longer patent life. Both are critically important for any new treatment for a rare disease, as the potential profits wouldn’t otherwise justify the development cost and risk.
Several other companies are working on anti-tau therapeutic antibodies, many of them aiming initially at PSP. Their ultimate Holy Grail is a treatment for Alzheimer’s, but it’s easier to conduct a clinical trial in PSP, as its progression is more readily predicted and measured. Furthermore, tau is the only protein known to aggregate in PSP, which makes that disease a simpler “model system” than AD, where both tau and beta-amyloid aggregate. The company furthest along this road is Bristol-Myers Squibb, whose tau antibody trial seeks 48 patients with PSP at 12 centers across the US and will start enrolling in a few weeks.
So I’m hoping for sunnier PSP clinic days soon!

Speech therapy in PSP?

The Lee Silverman Voice Training (LSVT) “Loud” program is a popular method used by speech/language clinicians to improve vocal volume and clarity in people with Parkinson’s disease.  I’ve never been all that enthusiastic about it because there is no literature demonstrating superiority to traditional forms of speech therapy for PD.  For another thing, I’m a little suspicious of its proprietary financial model, where a clinician pays anywhere from $300 (for a student) to $990 (for a professional) for a two-day course that yields a certificate permitting them to advertise that they offer LSVT.   The courses and certificates are available only from LSVT Global, Inc.

Potential evils of capitalism aside, it’s good to see someone finally trying to help the dysarthria of PSP.  Our heroes are a group in Rome headed by the well-regarded movement disorders authority Fabrizio Stocchi, MD PhD.  The paper‘s first author is Patrizio Sale, MD PhD. a neuro-rehabilitation specialist.  The work appeared in the European Journal of Physical and Rehabilitation Medicine.

The study compared the benefit of LSVT Loud in 16 patients with PSP to the same four-week course of treatment in 23 patients with PD.  Both groups did improve in most of the measures applied.  Probably the most positive result was in the reading task, where the maximum volume for the patients with PSP improved from an average of 82.5 dB to an average of 87.5 dB. Somewhat more modest benefits accrued for nonverbal phonation and for non-reading speech.

Unfortunately, there were no control patients receiving sham treatment, traditional treatment or no treatment.  We don’t know if the improvement will long persist, but the literature suggests that it does so in PD.  Equally important is that the study did not evaluate articulation — only volume.  Furthermore, the study was quite small, inviting flukey results.  Clearly, more work is needed, but for now, I’ll try sending some of my patients with PSP and hypophonia (low vocal volume) for LSVT.  I’ll let you know what happens.

A new PSP genetic risk factor screener

Genetic screening is emerging as a routine and necessary step in clinical research in the neurodegenerative diseases. If you’re looking for the cause of a family cluster, for example, you have to rule out the genetic variants already known to be associated with that disease. If you’re working up a geographical cluster of PSP, as my colleagues in France and I are, you have to look for a genetic founder effect before embarking on a difficult search for environmental causes, and the place to start is with gene variants already known to increase disease risk.
Pathological overlap among the various neurodegenerative diseases is another major current theme. For example, LRRK2 mutations can cause any of a number of pathologies, including PSP, and the tau H1 haplotype is associated with PSP, CBD and PD. It would therefore be convenient to have a single genetic screening device would allow different labs studying different diseases to compare or merge results.
Such a gizmo is now here. It’s a superset of Illumina’s Infinium HumanExome BeadChip called NeuroX. It tests for not only the standard 242,901 gene variants usable in studying any condition but also an additional 24,706 variants focusing on Alzheimer’s, Parkinson’s, MSA, ALS, FTD, multiple sclerosis, Charcot-Marie-Tooth disease, myasthenia gravis — and PSP. The chip is designed to allow easy substitution of subsequent versions of both the basic Illumina chip and easy addition of new neurological variants.
The first author of the report in Neurobiology of Aging is Mike Nalls and the senior author is Andrew Singleton, both of the NIH. The genetic variants included in the chip were derived from multiple genome-wide analyses over the past 20 years. Disclosure: I’m listed way down on the list of “authors” because I was a leader of “GenePD,” one of the consortia whose findings were used in constructing the new chip.  But I have no financial interest in the invention.
At a cost of $57 per sample plus the cost of the basic machine and technician time, you won’t have to be a drug company or the NIH to afford a statistically meaningful series; genetics core labs will be able to offer this as a routine procedure.