Young-onset Parkinson’s disease is a mystery to medical professionals. The onset of this condition typically occurs in those older than 60, but in this form the onset occurs between age 21-50. In those with the young-onset type, there is no family history of the disease and none of the known mutations associated with Parkinson’s cause it. For many years, this condition has confused medical professionals, but recently a study might have revealed the cause. Not only have they discovered a possible cause for young-onset Parkinson’s, but they may have found a treatment to stop the progression of the disease.
About Parkinson’s Disease
Parkinson’s disease is a progressive disorder that affects the central nervous system (CNS). It is characterized by its affect on movement through five different stages. As the disease progresses, severity increases. Stage one is characterized by subtle tremors on one side of the body. In stage two symptoms are more noticeable, with tremors and rigidity on both sides of the body. Stage three brings loss of balance and slow movement, while stage four makes it impossible for one to live independently. Stage five is the most severe, as patients cannot stand or walk. Hallucinations and delusions are common symptoms of this stage.
Parkinson’s disease occurs due to the death of motor neurons, some of which produce dopamine. Dopamine is important in the transmittance of messages to the muscles from the brain, so the loss of dopamine results in the loss of motor functions. Abnormal brain activity occurs when these neurons are lost and leads to Parkinson’s. Doctors do not know why these motor neurons die, but they do suspect a few factors that play a role, such as genetics, environmental factors like toxins, and Lewy bodies.
There are no FDA approved therapies for Parkinson’s, and treatment is symptomatic. There are dopamine substitutes, carbidopa-levodopa, MAO-B inhibitors, catechol-O-methyltransferase (COMT) inhibitors, anticholinergics, and amantadine.
The Cause of Young-Onset Parkinson’s Disease
In terms of Parkinson’s disease, doctors are unsure of the cause. They suspect that Lewy bodies may be the culprit, but are still unsure. When it comes to young-onset Parkinson’s, medical professionals knew even less about the cause. Until researchers at the Cedars-Sinai Medical Center began to research this disease, the healthcare world was in the dark.
Cedars-Sinai Medical Center in Los Angeles began using induced pluripotent stem cells (iPSCs) to study the causes of young-onset Parkinson’s. Researchers used these cells to convert blood cells from those with young-onset Parkinson’s and those without the disease into neurons capable of producing dopamine. They then compared the actions of the neurons in affected patients to those without Parkinson’s. They noticed three things.
The first observation included alpha-synuclein, which existed in higher levels in the nerve cells. The levels noticed were consistent with those in most forms of Parkinson’s. They also found that lysosomes were malfunctioning, which has the potential to lead to the buildup of alpha-synuclein. Lastly, levels of protein kinase C were heightened. This protein is responsible for the function of other proteins. All of these observations point towards a genetic cause rather than a sporadic one, which was the previous belief.
Researchers arrived at the conclusion that an inability to break down alpha-synuclein over the course of many years leads to an accumulation, which then kills neurons responsible for dopamine. They believe that alpha-synuclein accumulates for 20 to 30 years before symptoms emerge, which causes such an early onset of the disease.
Possible Treatment for Young-Onset Parkinson’s
As lysosomal dysfunction was observed in this study, researchers believe that PEP005 will be a viable treatment, as it has been known to activate lysosomes. It has been approved by the FDA for the treatment of pre-cancers of the skin. Medical professionals hope that if this compound is able to activate lysosomes, then the accumulations of alpha-synuclein will be broken down.
To test this hypothesis, researchers injected the compound into the brains of mice. It was shown to reduce the levels of alpha-synuclein. While the overall result did not surprise researchers, the methods did. PEP005 did not activate lysosomes. Instead, it activated proteasomal degradation, a protein breakdown pathway.
Not only did PEPP005 activate this pathway, but it also increased levels of an enzyme called tyrosine hydroxylase, which is involved with the production of dopamine. Levels of the protein kinase C were also lowered.
The issue with this treatment is that it is currently only available in a gel form. In order to make it a viable treatment for young-onset Parkinson’s disease, the compound will need to be converted into a different form so that it can be delivered to the brain.
Medical professionals are excited by the new knowledge that they have discovered through this study. A better understanding of this disease will increase doctor’s ability to treat Parkinson’s.
Find the source article here.
