A list of "disease modifying agents" for a tauopathy similar to CBD

[Swarfmaker]

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]

More on this from this article:

Rational therapeutic approaches to progressive supranuclear palsy

1. Maria Stamelou1,
2. Rohan de Silva2,
3. Oscar Arias-Carrión1,
4. Evangelia Boura1,
5. Matthias Höllerhage1,
6. Wolfgang H. Oertel1,
7. Ulrich Müller3 and
8. Günter U. Höglinger1

+ Author Affiliations

1. Department of Neurology, Philipps University, Marburg, D-35039,
Germany
2. Reta Lila Weston Institute of Neurological Studies, UCL Institute
of Neurology, London, WC1 N1PS, UK
3. Institut für Humangenetik, Justus-Liebig-Universität, Giessen,
D-35392,
Germany

1. Correspondence to: Günter Höglinger, Department of Neurology,
Philipps University, Rudolf-Bultmann Str. 8, D-35033 Marburg, Germany

* Received February 16, 2010.
* Revision received March 30, 2010.
* Accepted April 5, 2010.
http://brain.oxfordjournals.org/content/133/6/1578.long

Table 1 of the above article lists "puruvate". This must be a typo. In
the text, it refers to "pyruvate".