Parkinson’s disease progression slowed by antibody infusions

A drug that targets protein buildup associated with Parkinson’s disease could slow the progression of motor symptoms in patients with advanced Parkinson’s disease. While this holds promise as a disease-modifying treatment for Parkinson’s disease, it’s unclear whether the drug actually clears the protein from the brain.

The accumulation of a misfolded protein in the brain called alpha-synuclein 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 movement control.

While some existing treatments aim to relieve these symptoms by increasing dopamine levels in the brain, their long-term effectiveness is limited. So far, there are no approved disease-modifying therapies that can stop or slow the progression of Parkinson’s disease.

To solve this problem, Gennaro Pagano Dr. and colleagues from the Swiss pharmaceutical company Roche recruited 316 people thought to have early-stage Parkinson’s disease. Of those, 105 received a placebo intravenous infusion, while 211 received a low-dose or high-dose infusion of Roche’s drug prasinezumab, given as an injection every four weeks for a year.

Prasinezumab is an antibody designed to bind to misfolded alpha-synuclein aggregates in dopamine-producing neurons. “It is hypothesized that prasinezumab may reduce neuronal toxicity, prevent the transfer of pathological alpha-synuclein aggregates between cells and slow disease progression,” Pagano said.

While trial results initially suggested the antibody had no meaningful impact, the team later realized it might be effective in trial participants with more severe Parkinson’s disease.

These people have REM sleep behavior disorder, in which people have intense and often violent dreams, which is common in Parkinson’s disease; are taking MAO-B inhibitor medications to control symptoms; or have been rated as having symptoms by a specialist In the second stage of the scale (out of five stages), higher numbers indicate greater severity.

Another analysis showed that low and high doses of the drug affected participants with severe disease more than what was shown in the original study. It significantly reduced the rate at which participants’ motor symptoms worsened over a year compared with taking a placebo.

For example, on the Parkinson’s Disease Motor Symptom Rating Scale, those who took an MAO-B inhibitor and then received a placebo infusion had a score of 6.82 at the end of the year, while those who took both the inhibitor and prasinezumab had a score of 4.15.

“The results suggest that in people whose disease progresses more quickly, there is greater progression over time and a greater likelihood of potential treatment effects,” Pagano said. This may be because Parkinson’s disease progresses more quickly People with higher levels of misfolded alpha-synuclein in their brains may benefit more from drugs that might clear the protein.

However, Pagano said it was impossible to accurately assess what was happening in any of the participants’ brains because the researchers lacked a biomarker that would allow them to monitor how levels of misfolded alpha-synuclein changed.

Vinata Vidan Mai The UF Health researchers said a limitation of the study is that it did not assess whether alpha-synuclein is cleared from the brain. Without this, she said, the results cannot conclusively show that praxinizumab has a disease-modifying effect. Vedam-Mai said she 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.

Pagano said researchers could also study whether long-term administration of prasinizumab is effective in patients with milder forms of Parkinson’s disease.