The Lewis Katz School of Medicine at Temple University discovered that pharmacological chaperone therapy protects mice from Alzheimer’s disease (AD). Alzheimer’s is a chronic neurodegenerative disease with no cure yet. Abnormal clumps called amyloid-beta plaques and tangled fibers known as neurofibrillary or tau tangles create a brain disorder that slowly destroys memory and thinking skills. Additionally, loss of connections between neurons disrupts message transmission across the brain and to organs and muscles in the body.
Understanding Alzheimer’s Disease
To imagine Alzheimer’s, think of a wadded-up ball made of pieces of tape stuck together. Excessive proteins in the brain lose their shape and, like a tape ball, stick and clump together. This clumping blocks the transport of proteins to “recycling sites” within cells called endosomes. When trapped in the wrong cellular compartments, these proteins accumulate and disrupt important cellular functions.
Pharmacological Chaperones: A Promising Therapy
To maintain the brain’s molecular machinery, scientists developed small drug molecules called pharmacological chaperones. These molecules may play a key role in preventing and treating Alzheimer’s. The Temple University study, published in Molecular Neurodegeneration, showed that a chaperone drug can disrupt abnormal brain processes that damage neurons and cause memory loss in animals prone to Alzheimer’s.
How the Chaperone Drug Works
This chaperone drug restores levels of the sorting molecule VPS35, which helps move proteins out of endosomes and enables normal cell function. Dr. Praticò and colleagues previously identified that VPS35 clears harmful amyloid beta and tau proteins. In Alzheimer’s disease, VPS35 levels significantly decrease, causing protein clumps that disrupt neuron activity.
Study Results in Mice
Scientists tested the drug on young mice engineered to develop Alzheimer’s. The treated mice showed better memory and behaved like normal aging mice. In contrast, untreated mice developed Alzheimer’s symptoms. Brain exams confirmed fewer tau tangles and amyloid-beta plaques, restored VPS35 levels, and fully functional neuron synapses thanks to the chaperone therapy.
Benefits of Pharmacological Chaperone Therapy
“Compared to other Alzheimer’s treatments under development, pharmacological chaperones are inexpensive,” Dr. Praticò said. “Some of these drugs are already approved for other diseases, and they target cellular mechanisms instead of enzymes or receptors, which means fewer side effects. These factors make pharmacological chaperones very promising as novel Alzheimer’s treatments.”
Future Research Directions
Before starting clinical trials in humans, Dr. Praticò’s team will test the therapy on older mice that already show Alzheimer’s symptoms. This step will help determine if the treatment works for diagnosed cases.
Impact on Alzheimer’s Patients and Families
This research, funded in part by National Institutes of Health grants, brings hope to millions affected by Alzheimer’s. Affordable prevention and treatment could improve lives and reduce the healthcare cost burden on families and society.
How We Can Help Families
We assist families with loved ones affected by Alzheimer’s by creating legal plans that protect savings and homes if extensive long-term care becomes necessary.
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