Prasinezumab, a monoclonal antibody designed to target protein clumps in the brains of people with rapidly progressing Parkinson’s disease, has shown promise in reducing motor symptoms. It is the first experimental monoclonal antibody with such targeting, and a trial of 316 people suggests that it could be a path forward in fighting the disease. However, experts highlight that there are still a number of questions that need to be addressed through more rigorous clinical trials. Parkinson’s is characterized by significant neurological decline leading to tremors, motor control problems, and dementia. It is the second most common neurodegenerative disease after Alzheimer’s in the U.S., affecting at least 500,000 adults.
The PASEDENA study divided 316 participants into three groups, with some receiving different doses of prasinezumab and some receiving a placebo. After following all participants for 52 weeks, those who were taking prasinezumab showed a greater reduction of motor skills deterioration than those taking the placebo. A second phase of the trial is underway to examine the effects of the drug on individuals with a slower progression of the disease over a longer period of time. Another large phase 2 trial called PADOVA is also focusing on populations with rapidly progressing Parkinson’s. While the initial results of the study are promising, experts stress that larger, longer-term studies with diverse populations are needed for a more thorough evaluation of prasinezumab’s clinical utility in Parkinson’s disease management.
The potential of monoclonal antibodies as a treatment for Parkinson’s disease is still under investigation. These antibodies have not traditionally been used to address Parkinson’s symptoms due to challenges in targeting underlying mechanisms, particularly clumps of protein called alpha-synuclein aggregates. Prasinezumab was specifically designed to bind to these clumps and clear them from the brain. However, Daniel Truong, MD, points out that monoclonal antibodies have not yet been approved specifically for the treatment of Parkinson’s due to the complexity of the disease and the need for personalized treatment approaches.
Despite the promising results of the PASEDENA trial, there are challenges in using monoclonal antibodies as a treatment for Parkinson’s, according to Truong. These drugs have large molecular sizes that may prevent them from crossing the blood-brain barrier, and the disease itself varies from person to person. Parkinson’s disease is heterogeneous, with variability in symptoms, disease progression, and underlying pathology among individuals. Personalized medicine approaches that consider individual variability in disease pathology and genetics may be necessary to optimize treatment outcomes.
Allder recommends several approaches besides monoclonal antibodies that can help address Parkinson’s symptoms. Deep brain stimulation, MAO-B and COMT inhibitors, anticholinergic drugs, and glutamate modulators can help adjust the chemical imbalances contributing to disease progression, such as a lack of dopamine. Research is ongoing to explore new treatments that protect the brain. Truong emphasizes the need for further research given the small sample size and relatively short period of time covered in the PASEDENA trial. The findings of the study may not be generalizable to all individuals with Parkinson’s disease, as the study population may have specific characteristics or be enriched for certain subgroups.