GEN Exclusives

More »

GEN News Highlights

More »
Apr 4, 2013

Potential Prion Disease Therapy Uncovered

  • Scientists have identified a pair of drugs already approved for human use that show antiprion activity, and one of them may hold promise in treating fatal disorders, such as Creutzfeldt-Jakob disease (the human equivalent of mad cow disease), says the team at the Florida campus of The Scripps Research Institute. The two compounds are already marketed as the drugs tacrolimus and astemizole.

    The team developed a screening technique, the PrP–FRET-enabled high-throughput assay (PrP–FEHTA), to uncover compounds that decrease the amount of the normal form of the prion protein (PrP, which becomes distorted by the disease) at the cell surface. The scientists found that tacrolimus and astemizole reduced PrP on cell surfaces by approximately 70% in the screening and follow-up tests.

    Tacrolimus is an immune suppressant widely used in organ transplantation. Tacrolimus could prove problematic as an antiprion drug, however, because of issues including possible neurotoxicity, the reseachers report. However, astemizole is an antihistamine that has potential for use as an antiprion drug. While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in more than 30 countries and has a well-established safety profile. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration, the team says. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice.

    Scripps professor Corinne Lasmézas, Ph.D., noted that astemizole appears to stimulate autophagy, the process by which cells eliminate unwanted components. “Autophagy is involved in several protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases,” she says. “So future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders.”

    The study noted that eliminating cell surface PrP expression could also be a potentially new approach to treat Alzheimer’s disease, which is characterized by the build-up of amyloid β plaque in the brain. PrP is a cell surface receptor for Aβ peptides and helps mediate a number of critical deleterious processes in animal models of the disease.

    The scientists also note that their results validate PrP-FEHTA as a method to identify antiprion compounds and FEHTA as a drug discovery platform.

    The study was published this week online ahead of print by the journal Proceedings of the National Academy of Sciences. The article is called “Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents”.


Readers' Comments

Posted 04/04/2013 by Ed Gehrman

You may also want to consider this:
Dr. Frank O. Bastian, MD, a professor of pathology, has published numerous research articles relating to the etiology of Creutzfeldt-Jakob Disease and also edited a book entitled "Creutzfeldt-Jakob Disease and Other Transmissible Spongiform Encephalopathies". His research indicates that Spiroplasma bacteria causes CJD and other TSE, and insists that the infection-related protein that most researchers refer to as a "prion" is produced by the host in response to the infection and is not the causative agent. Prions are thought to be self-replicating proteins. Some researchers believe prions are the cause of CJD and related illnesses because they have found prions in brain tissue from people with TSE. Bastian states that a shortcoming in the prion theory is that CJD and scrapie can be transmitted without prions. Brain material from which the prion has been removed with antibodies can still infect animals. Prion researchers have jumped to conclusions and have not considered any other possibilities. Spiroplasma may be inducing the formation of the prion protein to protect itself from the immune system. The immune system is very important in the pathogenesis of CJD. The agent replicates in the spleen and lymph nodes and occasionally causes an immunologic reaction. Auto-antibodies are characteristically seen in the late stages of experimental and naturally occurring disease. I believe the above information also applies to Alzheimers.
We will never find a cure for either TSE or Alzheimers until we understand their relationship to Spiroplasma infection.

Add a comment

  • You must be signed in to perform this action.
    Click here to Login or Register for free.
    You will be taken back to your selected item after Login/Registration.

Related content

Jobs

GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.
 Searching...

Unable to get Jobs Listings.

More »

GEN Poll

More » Poll Results »

Biosimilars

Compared to the original biologics, do you think biosimilars run the risks of being less effective and causing more side effects?