Temple University Preclinical Investigators Reveal Pharmacological Chaperone Therapy May Prevent Alzheimer’s Disease in Mice

Temple University Preclinical Investigators Reveal Pharmacological Chaperone Therapy May Prevent Alzheimer’s Disease in Mice

Preclinical researchers at Temple University’s Lewis Katz School of Medicine continue the battle against Alzheimer’s disease—a continuous effort to study novel approaches and experimental therapies that hopefully will some day develop a way to stop this insidious and debilitating disease that ultimately robs people of their most precious possession—their memories. The Temple University team recently published promising results in the journal Molecular Neurodegeneration. Although still in preclinical stage (e.g. pre-IND), this nonetheless merits attention for those interested in Alzheimer’s disease research.

The Lead Investigator

The Temple University senior investigator, Domenico Praticò, the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research, Professor in the Departments of Pharmacology and Microbiology and Director of the Alzheimer’s Center at Temple (ACT) at the Katz school, drives attention on the use of a drug known as “chaperone therapy” in a preclinical study using mice.

What is Chaperone Therapy?

A pharmacological chaperone or pharmacoperone is a drug that acts as a protein chaperone. That is, it contains small molecules that enter cells and serve as a molecular scaffolding in order to cause otherwise-misfolded mutant proteins to fold and route correctly within the cell

Mutation of proteins often causes molecular misfolding, which results in protein misrouting within the cell. Accordingly, mutant molecules may retain proper function but end up in parts of the cell where the function is inappropriate, or even deleterious, to cell function. Misfolded proteins are usually recognized by the quality-control system of the cell and retained (and often destroyed or recycled) in the endoplasmic reticulum

Pharmacoperones correct the folding of misfolded proteins, allowing them to pass through the cell’s quality-control system and become correctly routed. Since mutations often cause disease by causing misfolding and misrouting, pharmacoperones are potentially therapeutic agents, since they are able to correct this defect.

As reported on by a University of Maryland at Baltimore, IMET, in a Columbus Center study titled “Alzheimer’s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy” they conclude that although the roles and mechanisms of action of chaperones associated with Alzheimer’s disease are still not fully understood, sufficient evidence exists to encourage the development of therapeutic strategies targeting them. This approach can include blocking their activity in case they promote disease progression or the boosting of their performance when they are protective. This latter approach represents a positive chaperonotherapy, which could possibly include chaperone replacement via gene or protein administration. If a chaperone is found to be blocked or eliminated then negative chaperonotherapy strategies are considered.

The Preclinical Study

The study, published in the journal Molecular Neurodegeneration, highlights the ability of a new drug treatment that shows potential in the prevention of the buildup of certain proteins accumulating in the brain.

As reported by Temple Health, the lead investigator, Praticò, and team studied the mice upon administration of the chaperone therapythey measured how the drug influenced the levels of certain proteins associated with Alzheimer’s disease. In the mice, the drug actually disrupted the deteriorating processes associated with the disease, and the mice’s brains remained healthier.

Praticò noted, “Our chaperone drug specifically restored levels of sorting molecule known as VPS35.” Apparently, VPS35 represents a critical element in the cellular processes involved with the removal of the amyloid beta and tau proteins—which of course are known to be associated with Alzheimer’s disease.

Why are Chaperones Promising?

For one the therapy used by the Temple team, according to their recent news, has a track record with other diseases.  Praticò explained, “Relative to other therapies under development for Alzheimer’s disease, pharmacological chaperones are inexpensive, and some of these drugs have already been approved for the treatment of other diseases.” He continued, “These drugs do not block an enzyme or receptor but target a cellular mechanism, which means that there is much lower potential for side effects.”

About Alzheimer’s Center at Temple

The Alzheimer’s Center at Temple University was created with the appointment of Dr. Domenico Praticò as the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research. ACT will integrate research, training, clinical and educational activities in order to study the pathophysiology of Alzheimer’s disease and related disorders, discover the mechanisms responsible for their onset and progression, and develop effective treatment strategies with the ultimate goal of curing those diseases. ACT will build upon the long-standing tradition of excellence in biomedical research and education of the Lewis Katz School of Medicine at Temple University.

Lead Research/Investigator

Domenico Praticò as the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research

Call to Action: Interested in learning more about this study? See the actual published article in the journal Molecular Neurodegeneration. TrialSite News monitors preclinical and clinical investigators worldwide, including Domenico Praticò at Temple University. For updates on his research, sign up for the daily newsletter.