Injection of antibodies can help slow down the advancement of Parkinson’s disease

Drugs that target protein accumulations associated with Parkinson's disease may slow the progression of motor symptoms in patients with advanced Parkinson's disease. This shows potential as a disease-modifying treatment for Parkinson's disease, but it is unclear whether the drug actually removes the protein from the brain.

Accumulation of a misfolded protein called alpha-synuclein in the brain has long been thought to be the underlying cause of Parkinson's disease. This results in the loss of neurons that produce the neurotransmitter dopamine, which is involved in motor control.

Some existing treatments aim to alleviate these symptoms by improving dopamine levels in the brain, but their long-term effects are limited. To date, there are no approved disease-modifying treatments to stop or slow the progression of Parkinson's disease.

In an effort to counter this, Gennaro Pagano Swiss pharmaceutical company Roche and colleagues recruited 316 people who appeared to have early stages of Parkinson's disease. Of these people, 105 received an intravenous infusion of a placebo, and 211 received a low or high dose of Roche's drug plasinezumab every four weeks for a year.

Placinezumab is an antibody designed to bind to aggregates of misfolded alpha-synuclein within dopaminergic neurons. “It is hypothesized that placinezumab may reduce neurotoxicity, prevent cell-to-cell movement of pathological alpha-synuclein aggregates, and slow disease progression,” Pagano says.

Trial results initially suggested the antibody had no significant effect, but the team later realized it may have an effect in trial participants with more severe forms of Parkinson's disease. I did.

These people suffered from rapid eye movement sleep behavior disorder, which causes intense, often violent dreams that are common in Parkinson's disease. He was taking a drug called an MAO-B inhibitor to manage his symptoms. Or, he has been rated by an expert at 2 out of 5 on a symptom scale, with higher numbers indicating greater severity.

Additional analyzes showed that both low and high doses of the drug had greater effects than seen in the first study, especially among critically ill participants. The rate at which participants' motor symptoms worsened over a one-year period was significantly reduced compared to those taking a placebo.

For example, based on the Parkinson's Disease Rating Scale for Motor Symptoms, patients who took an MAO-B inhibitor and then received a placebo infusion had a score of 6.82 at the end of the year, compared to Patients who took the drug had a score of 4.15.

“These results suggest that potential treatment benefits may be more likely to be achieved in populations that experience greater deterioration over time and more rapid progression,” Pagano says. This is because patients with Parkinson's disease, which progresses more rapidly, have higher amounts of misfolded alpha-synuclein in their brains, so they may benefit more from drugs that can remove this protein. There is a possibility.

However, Professor Pagano said researchers lacked a biomarker that could monitor how participants' levels of misfolded alpha-synuclein changed, so it was unclear what was happening in the participants' brains. He said it was not possible to make an accurate assessment.

Vinata Vedam Mai Researchers at the University of Florida Health say a limitation of the study is that it did not assess whether alpha-synuclein was cleared from the brain. Without this, she says, the results cannot conclusively show that plasinezumab is disease-modifying. Vedam-Mai said he would also like to see long-term data to better assess the drug's safety and effectiveness. No serious adverse events occurred in the latest trial.

Researchers could also investigate whether plasinezumab, when taken over a long period of time, is effective for patients with mild Parkinson's disease, Pagano said.