Researchers Develop "Two-Headed" Drug to treat Parkinson's Disease

[Baron1]

Although the following research is in its infancy, it has merit and looks promising.

In particular that they want to try and make it a oral bio-active medicine.

Researchers have created a ‘two-headed’ drug that prevents the production of the toxic protein linked to Parkinson’s disease before destroying the RNA machinery that makes it. The novel drug may be a way of slowing or even stopping the disease’s progression.

Current Parkinson’s medications replace the dopamine that’s depleted as neurons responsible for producing the neurotransmitter are lost due to an accumulation of alpha-synuclein. While the drugs improve the quality of life of people with Parkinson’s, they are only managing the symptoms of the disease; they’re not a cure.

Rather than alleviating symptoms, the researchers wanted their drug to target the toxic alpha-synuclein protein at the heart of Parkinson’s disease. It is not an easy task, as alpha-synuclein has been considered ‘undruggable,’ a challenging drug target due to its unruly, disorganized form and lack of druggable structures.

Targeting the RNA needed to build the toxic protein may be an optimal strategy to slowing or even stopping disease progression is there strategy.

Proteins are assembled in the body’s cells through a process that involves the reading and translation of a gene, the transport of that information from the cell’s nucleus to its cytoplasm via messenger RNA (mRNA), and ribosomes, the cellular machinery responsible for making proteins. Each ribosome is made up of two subunits that lock around the mRNA and travel along its length, reading its protein-making ‘instructions’.

The researchers started with Synucleozid-2.0, a drug-like small molecule that binds to a section of alpha-synuclein (SNCA) mRNA that tells the ribosome to start assembling the protein. The drug inhibits alpha-synuclein translation by preventing ribosomes from assembling onto SNCA mRNA (that’s head number one). The RNA-binding small molecule was converted into a ribonuclease-targeting chimera (RiboTAC) that selectively degrades cellular SNCA mRNA (head number two). Hence, the drug’s two-headed – chimeric – effect is realized.

RNA sequencing and proteomics studies demonstrated that the drug, which the researchers have called Syn-RiboTAC, reduced the mRNA’s protein levels and rescued the expression of around 50% of the genes that were abnormally expressed in dopamine-producing neurons derived from Parkinson’s patient-derived induced pluripotent stem cells (iPSCs).

“In Parkinson’s mouse models, we see that reducing alpha-synuclein by even 25% is therapeutically beneficial,” said Yuquan Tong, the study’s lead author. “In studies from induced neurons of Parkinson’s patients, we see the Syn-RiboTAC strategy reduces alpha-synuclein production by about 50%. We saw that adding the RiboTAC produces a significant gain in potency.”

pnas.org/doi/10.1073/pnas.2...

Best Wishes to All

[jeffreyn]

See also this very recent post.

healthunlocked.com/cure-par...