New tool developed to diagnose dementia cases
Molecular tool removes toxic protein
From successfully achieving the first remission of a pediatric cancer case in 1948, to creating the most revolutionary medical achievements WorldCare Consortium® medical second opinion (MSO) providers, Dana-Farber and Massachusetts General Hospital have successfully created a molecular tool that helps study the accumulation of toxic proteins in patient’s brain cells who suffer from multiple dementia conditions. This molecular tool is referred to as QC-01-175. In the journal eLife, this tool was described as a way to diagnosis Alzheimer’s and related neuro-degenerative disorders.
What does this mean?
First, what exactly were these researchers looking for? Well, to start they were interested in better understanding the role aberrant proteins play in dementia cases. Examining and understanding that the protein tau plays a significant role in the binding and shaping of cell stabilizing structures known as microtubules. This is important because it is believed that abnormal tau accumulates in the brain cells linked to the progression of dementia conditions such as Alzheimer’s, frontotemporal dementia (FTD) and progressive supranuclear palsy. The hope of this research was to develop a tool that could diagnose dementia cases as well as eliminating the toxic tau safely.
How does it work?
Like many breakthroughs in modern medicine, this new tool comes from modifying an older tool called T807, which was a molecular probe used in positron emission therapy (PET). The original device was used to scan for Alzheimer’s and other tau-related diseases by tagging the probe with a radioactive isotope. When this binds with the abnormal tau, a PET scan can then detect the disease. Modifying this probe with an E3-ligase recruiting ligand molecule allows the probe to bind to the cell’s machinery destroying unwanted cells. Next, this newly-revised probe enables the abnormal tau protein to be bound to ubiquitin protein, which essentially labels the abnormal protein as cellular trash. The modified probe QC-01-175 acts as a tool for delivering toxic tau into the cells disposal system.
The result of all this work was a probe that succeeded in what researchers aimed to achieve. Abnormal tau was removed while having minimal effects on tau in the neuron of healthy volunteers. This is the first successful technique that targets the damaged tau protein from human neurons. Secondly, this represents how targeted protein degradation can transform a protein binder into a molecule with pharmacological effects on cells. This strategy is being explored in treating a more extensive range of proteins that drive neurodegeneration; which is still in the animal testing stage of its research.
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