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YOPD

Early-Onset Parkinson’s Could Be Starting Before Birth

A study from U.S.-based Cedars-Sinai research teams has identified mechanisms for young-onset Parkinson’s to before birth, while also showcasing a drug that might potentially help correct abnormalities.

About 10% of all people with Parkinson’s are diagnosed between the ages of 21-50. In this case, they are classified as having early or young-onset Parkinson’s (YOPD).


Time Travel through Stem Cells

IPSC

To conduct the research study, special stem cells were generated, known as induced pluripotent stem cells (iPSCs), from the cells of patients with early-onset Parkinson's. 

iPSCs can give researchers a crucial window to look “back in time” by converting adult cells to a primitive embryonic state.

Parkinson’s affects the part of our brain that produces the chemical dopamine. Dopamine contributes to feelings of satisfaction and our ability to be attentive. The chemical gives us control over the movements our body makes - hence the involuntary shaking of limbs from some people who have Parkinson’s.

In particular, a protein found in our brain called alpha-synuclein regulates the release of dopamine.  For reasons that we do not quite understand, however, this protein clumps together and becomes toxic. The resulting brain cell damage leads to a host of neurodegenerative diseases, including Parkinson’s and other Parkinsonism conditions. 

Cedars-Sinai researchers inspected how dopamine neurons might have functioned from the very start of the life of people who were later diagnosed with YOPD.


Understanding Abnormalities

Parkinsonism

Two key abnormalities were reported by the researchers, including the accumulation of the alpha-synuclein protein as well as malfunctioning lysosomes.

Lysosomes are cell structures that act as 'trash cans' for the cell to break down and dispose of proteins. Researchers believe that their malfunctioning could be causing alpha-synuclein to build-up.

Another abnormality found was the presence of elevated levels of an enzyme called protein kinase C. However, the role of active versions of this enzyme in Parkinson’s is not yet clear.

"It appears that dopamine neurons in these individuals may continue to mishandle α-synuclein over a period of 20 or 30 years, causing Parkinson's symptoms to emerge", said a senior study author, Clive Svendsen.


Exploring a Skin Cancer Drug

YOPD Study

The researchers from Cedars-Sinai Medical Center also mentioned that they are investigating an FDA-approved skin cancer drug called PEP005, which is an agonist of the protein kinase C enzyme mentioned above. 

Researchers believe the drug might help correct abnormalities by reducing elevated levels of the alpha-synuclein protein.

This research provides hope that through early detection and action, the condition could be prevented in at-risk individuals.


SOURCE: Nature Medicine Journal, iPSC modeling of young-onset Parkinson’s disease reveals a molecular signature of disease and novel therapeutic candidates