The following article is about PSP, but the "disease modifying agents" may apply
to other tauopathies. Some of these we have already discussed. Some are new...

Brain. 2010 May 14. [Epub ahead of print]

Rational therapeutic approaches to progressive supranuclear palsy.

Stamelou M, de Silva R, Arias-Carrión O, Boura E, Höllerhage M, Oertel WH,
Müller U, Höglinger GU.
Department of Neurology, Philipps University, Marburg, Germany.

Abstract
Progressive supranuclear palsy is a sporadic and progressive neurodegenerative
disease, most often presenting as a symmetric, akinetic-rigid syndrome with
postural instability, vertical supranuclear gaze palsy and frontal lobe
deficits. It belongs to the family of tauopathies and involves both cortical and
subcortical structures.

Although the exact pathophysiology is not yet fully understood, several lines of
evidence point to a crucial contribution from both genetic predisposition and
mitochondrial dysfunction.

Recently gained insights into the pathophysiology of this disease have led to
several hypothesis-driven therapeutic approaches aiming at disease-modification
rather than mere symptomatic neurotransmitter-replacement therapy.

Agents targeting mitochondrial dysfunction have already shown a positive effect
in a phase II study and further studies to verify and expand these results are
ongoing. Clinical studies with agents targeting tau dysfunction such as
tau-kinase inhibitors, tau-aggregation inhibitors and microtubule stabilizers
are in preparation or ongoing.

This review presents the current pathophysiological concepts driving these
exciting therapeutic developments.

PubMed ID#: 20472654

Table 1 - Clinical trials aiming at disease modification in PSP

Substance: Coenzyme Q10
Target: Mitochondrial dysfunction
Mechanism: Complex I cofactor
Phase II trial: Significant improvement (Stamelou et al, 2008)
Phase III trial: Recruiting (NCT00382824 on clinicaltrials.gov)
[The dosage for CoQ10 is reported to be 2400mg/day. Please research this
carefully.]

Substance: Puruvate, creatine, niacinamide
Target: Mitochondrial dysfunction
Mechanism: Multifunctional cocktail
Phase I trial: Active (NCT00605930 on clinicaltrials.gov)
[Niacinamide has been discussed. 2000mg per day, 500mg at a time, would be
about right for an average person. We will have to research creatine and
puruvate.]

Substance: Lithium
Target: Tau dysfunction
Mechanism: GSK-3beta inhibitors
Phase I trial: Stopped because of poor tolerability (NCT00703677 on
clinicaltrials.gov)

Substance: Valproic acid
Target: Tau dysfunction
Mechanism: Aggregation inhibitors
Phase II trial: Active (NCT00385710 on clinicaltrials.gov)
[I don't know what this one is. I will have to research it.]

Substance: Nypta
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Phase II trial: Recruiting (NCT01049399 on clinicaltrials.gov)

Substance: Methylthioninium chloride
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Phase II trial: Significant improvement in Alzheimer's disease (Wischik et al,
2008); PSP not studied
[This is a form of methylene blue. See also info on Rember.]

Substance: Danuvetide
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Phase II trial: PSP study in preparation
[a.k.a NAP or AL-108]