This review article was written by researchers at Allon Therapeutics (manufacturers of the experimental medication davunetide, which is currently in clinical trials around the world) and some of the world’s top progressive supranuclear palsy (PSP) experts.
The theory behind davunetide, animal research, and clinical research (in humans with amnestic mild cognitive impairment) were reviewed in a webinar for laypeople held last year (2-8-11). See my notes on the webinar here:
https://www.brainsupportnetwork.org/davunetide-research-update-webinar-2-8-2011/
One of the co-authors of this paper was the Allon Therapeutics presenter of the webinar, Dr. Bruce Morimoto.
There were two new bits of info for me in the review of davunetide animal and human research:
* davunetide has also been tested in alpha-synuclein models, so it may have relevance to Parkinson’s Disease, Multiple System Atrophy, and Dementia with Lewy Bodies
* davunetide has also been tested in an exploratory trial in cognitive impairment in schizophrenia.
The review article’s section on “Challenges and opportunities for clinical trials in PSP” was fascinating. Some aspects of this section were reviewed by Dr. Adam Boxer from UCSF at a conference in LA last year for PSP families. He explained why pharmaceutical companies are inclined to conduct research with PSP patients rather than Alzheimer’s patients. The info provided in the article takes all of what Dr. Boxer said a step further. The authors explain why the davunetide trial going on now in PSP limited the patients to those with the classic form of PSP, called Richardson’s syndrome.
The authors referred to German research which indicates that although both PSP “patients and relatives frequently seek medical treatment, their willingness to participate in clinical trials has been surprisingly low historically.” Indeed, I only know of one caregiver group member whose wife participated in the lithium trial, only one caregiver group member whose father participated in the transcranial magnetic simulation study, and very few group members who have participated in the NIH-funded study of genetic and environmental causes of PSP. Unfortunately, participating in these trials has not been easy. On the other hand, probably half of our caregiver group members donate their family member’s brain upon death, which is certainly one vital means of enabling PSP research.
By the end of 2012, we should see a paper on the davunetide clinical trial and the Nypta clinical trial. These are exciting times for the PSP community.
I’ve copied the abstract of the review article below.
Robin
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Neuropsychiatric Disease & Treatment. 2012;8:85-93. Epub 2012 Feb 9.
Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy.
Gold M, Lorenzl S, Stewart AJ, Morimoto BH, Williams DR, Gozes I.
Allon Therapeutics Inc, Vancouver, BC, Canada.
Abstract
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution.
Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia.
There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide’s efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication.
This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.
PubMed ID#: 22347799 (see pubmed.gov for this abstract only)