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Wednesday, May 15, 2024

Advances in Understanding Parkinson’s Disease


Local and international research on diagnosis and treatment

Treating and studying Parkinson’s disease is uniquely challenging because the disease is quite advanced before symptoms are clearly identifiable. In Parkinson’s disease, a group of nerve cells that produce dopamine, an important chemical communication molecule, deteriorate over time. By the time symptoms such as tremor, rigidity and slowness of movement appear, up to 80% of this group of cells, called the substantia nigra, have died. Current treatment is to increase the levels of dopamine which decline after this cell death.

Another hallmark of Parkinson’s disease is the formation of Lewy bodies.

Lewy bodies are deposits of abnormal protein called alpha-synuclein in the brain. Lewy body formation is a marker for nerve cell degeneration and is associated with chemical changes like loss of dopamine. These changes can lead to problems with movement, thinking, behavior and mood.

Last year, an international team of scientists identified an early biomarker of Parkinson’s disease based on abnormal alpha synuclein. A biomarker is a measurable substance in the body that is a sign of normal or abnormal processes. In this study, they could detect abnormal alpha synuclein before symptom onset. Early identification is a huge advance for the diagnosis, study and treatment of Parkinson’s disease because it expands the window of time available for research and intervention before large scale cell death occurs. While the test for this biomarker is not yet widely available, development has been fast-tracked by study sponsors including the Michael J. Fox Foundation.

In addition, in April 2024, another group from across the globe showed that the use of an existing diabetes drug slowed the progression of motor symptoms in Parkinson’s disease.

The study, recently published in the New England Journal of Medicine, evaluated the effectiveness of the medication Lixisenatide using a blinded, placebo-controlled design. After monitoring patient symptoms for a year, they found that the placebo group, or patients who were not given the medication, showed moderate motor progression or worsening of movement impairment over time.

However, the group receiving Lixisenatide did not show any progression of motor symptoms.

The mechanism is not fully understood yet, but previous work has shown a link between the insulin resistance of diabetes and the accumulation of alpha synuclein Lewy bodies. Current treatment boosts low levels of dopamine to reduce symptoms. Lixisenatide is the first drug that appears to treat the disease process. More study is needed, but because the drug is FDA-approved to treat diabetes, it could become available to treat Parkinson’s disease soon.

Another new treatment that is getting a lot of attention is focused ultrasound.

This procedure was developed as a potential alternative to the very effective deep brain stimulation procedure approved for the treatment of Parkinson’s disease by the FDA in 2002.

Deep brain stimulation, or DBS, is a surgical procedure involving the placement of a wire, or electrode, into one of the areas of the brain that malfunctions in Parkinson’s disease. A gentle current is run through the electrode that disrupts the abnormal activity of the local neurons. While invasive, it is highly effective and can be adjusted over time.

Focused ultrasound also disrupts these abnormal signals using high-intensity sound waves to generate heat, destroying the malfunctioning cells connected to tremor. It was approved to specifically treat the tremors of Parkinson’s disease in 2018. Last year, a double-blinded, placebo-controlled study by another international team of scientists was published in the New England Journal of Medicine showing that about 70% of people showed a significant positive response at three months and 78% of those patients still showed a response at 12 months. However, side effects were noted as a concern by researchers.

Focused ultrasound is not yet available in the Shreveport region but can be accessed in some larger metropolitan areas. If you have tremor-dominant Parkinson’s disease and are interested in learning more, talk with your neurologist or call us at the Center for Brain Health.

The people of North Louisiana are also contributing to exciting genetic breakthroughs for Parkinson’s disease. Last year, the LSU Health Shreveport Center for Brain Health began enrolling volunteers in a genetic study called Black and African American Connections to Parkinson’s disease, or BLAAC PD. The study is designed to learn more about gene changes that may cause Parkinson’s disease.

There are significant racial differences in the incidence of Parkinson’s disease that may help us better understand disease mechanisms. However, to date, 90% of genetics studies related to Parkinson’s disease have involved populations of European ancestry, while the genetic impact on Parkinson’s disease susceptibility in Black and African American individuals has not been well studied. Parkinson’s disease appears to be less common in Black compared to White populations.

Early results are promising, showing a novel link between age of disease onset and Parkinson’s disease risk associated with the GBA1 (a gene) locus, that is more common in Black than White individuals with Parkinson’s disease. Mutations to the GBA (glucocerebrosidase) gene have previously been linked to increased risk of Parkinson’s disease and related disorders. Better understanding these genetic differences can teach us more about disease vulnerability and neural protection and is key for precision medicine.

LSUHS is currently recruiting volunteers to participate in the BLAAC-PD study. People who meet the following criteria are eligible to be a part of this study:

• Age 18 or older

• Identify as Black or African American

• Do or do not have Parkinson’s disease

There is no cost to participate, and participants will be compensated.

We are also pleased to provide access to the Parkinson’s disease GENEration: Mapping the Future of Parkinson’s Disease study sponsored by the Parkinson’s Foundation. It is a national study available to anyone diagnosed with Parkinson’s disease. Participants will receive results from genetic testing as well as genetic counseling. These services are free. This study may help improve the management of one’s Parkinson’s disease in the future, provide information about a family’s risk of Parkinson’s disease and improve Parkinson’s care and research for those who have or will have Parkinson’s disease.

To learn more or to participate, please contact Dr. Elizabeth Disbrow and her team at the Center for Brain Health, 1521 Wilkinson St., (318) 813-3610, CB-HResearch01@lsuhs.edu or visit www.lsuhs.edu/cbh.

Elizabeth Disbrow, PhD, is the director for the Center for Brain Health and professor of neurology at LSU Health Shreveport.


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