This New Treatment Could Stop Parkinson’s Disease

Researchers at the Johns Hopkins University are now a step closer to treating Parkinson’s disease. The team recently reported that they have identified a protein which assists toxic natural aggregates to spread from one brain cell to another, in mice model. Interestingly, after understanding the mechanism of cell to cell transfer of toxic aggregates that gives rise to Parkinson’s disease, these experts have also identified a way to block this protein’s activity.

In a news release, Ted Dawson, MD, PhD, Director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine and study’s co-author, said that the new findings elaborate on how the aggregates of alpha-synuclein protein enter the brain cells. He added that through observing the autopsies from Parkinson’s disease patients, they know that abnormal clumps of alpha-synuclein are present which are likely to be responsible for the death of dopamine-producing brain cells.

The crucial findings of this study which can lead to the formulation of new therapeutics for treating Parkinson’s disease was also published in the Science journal, today on 30th September.

According to the Parkinson’s Disease Foundation, more the 10 million people across the globe are living with Parkinson’s disease. Although, the disease is frequently diagnosed in older adults, 4% of the cases are diagnosed in people before the age of 50. Characterized by shaking limbs, stiffness of muscles and slowness of movement (bradykinesia), it is a neurodegenerative brain disorder which takes years to progress and manifest its symptoms.

However, years of painstaking research has enabled neurology experts to find out underlying causes of this multifactorial disease. While there are genetic and environmental factors involved in giving rise to the disease, the ultimate reason leading to the symptom manifestation of the condition is the depletion of dopamine in the neural cells. Studies show that when 80% of the dopamine producing cells die, the disease begins to exhibit its debilitating effects on the health.

Dopamine is responsible to control and coordinate body movements and once this depletion reaches severe levels, the Parkinson’s disease diagnosis becomes inevitable. Out of the many reasons leading towards this neurotransmission depletion, the researchers of this study investigated the role of alpha-synuclein which is present in the clumps of disease markers, known as lewy bodies.

Alpha-synuclein protein is found in the tips of the neural cells in the presynaptic terminals and under normal functioning, the protein is said to play a role in maintaining sufficient supply of synaptic vesicles and regulate the release of dopamine.

A few years ago, researchers from the Goethe University in Germany also identified the role of alpha-synuclein in triggering the condition. Their studies gave evidence, suggesting that the disease advances as these proteins move from the lower region of brain to the higher regions of brain which control the memory and reasoning. As these protein molecules move from one brain cell to the other, they form clumps and move towards dopamine producing cells to hamper their activity.

Could This Be An Effective Treatment For Parkinson’s Disease?

Fortifying upon this evidence, the team of this recent study delved into investigating the ways in which these proteins are taken in by brain cells, which initiate the deleterious effects of Parkinson’s disease.

Cells are highly specialized and specific on the substance movement, in and out of the cells. Thereby, the experts hypothesized that the transmembrane receptors which work like a “lock in a door” for the cell are actually behind the cell to cell transfer of the protein clumps.

The researchers initially found that the synuclein aggregate could not enter a line of human brain cancer cells which were grown in the laboratory. The next step was to isolate the genes for transmembrane receptors and insert them into the cells, one after the other, to observe the role of these receptors on the uptake of synuclein aggregates.

By using recombinant alpha-synuclein preformed fibrils (PFF) as a model, three clones of transmembrane receptors were identified, these included lymphocyte-activation gene 3 (LAG 3), amyloid beta precursor-like protein 1 (APLP1) and neurexin 1β. Out of these receptors, the LAG3 receptor (having an endocytosis role) was found to have highest permeability to synuclein aggregates as compared to non-clumped alpha-synuclein (synuclein monomers). The LAG3 showed high affinity for synuclein aggregates while the synuclein monomers did not bind to the LAG3.

To further validate these findings, mice were bred under laboratory conditions which did not carry the gene for encoding LAG3 receptor. These mice were injected with alpha-synuclein aggregates and the progression of disease was monitored. Researchers know from previous work that mice begin to show Parkinson’s-like symptoms soon after they are injected with the alpha synuclein aggregates and half of the dopamine cells die in six months.

Interestingly, this group of mice did not develop the disease because the brain cells did not take up the alpha-synuclein aggregates and they were completely protected from these synuclein clumps.

Excited by these findings, these researchers said that similar protective effects in cultured neurons are also received by LAG3 blocking antibodies, which is a positive sign of formulating effective therapeutics for Parkinson’s disease. It was also found by team that antibodies which block LAG3 are currently under clinical trials to strength immune system of cancer patients during therapy. They added that if the drug successfully reached the pharmacies around us, then the process of testing them as a potential therapy for Parkinson’s disease can take place soon.

While these researchers are hoping to continue their work in testing the LAG3 antibodies and exploring the role of LAG3 in more detail, we can see this study as a huge step towards combating Parkinson’s disease.

Leave A Reply

Your email address will not be published.