Reacción a "Reactions: Analysis shows monoclonal antibody slows motor symptoms in patients with rapidly progressing Parkinson's disease"

The study design is of good quality; you don't publish in a journal of this level if the study is not well done. A different issue is whether the design is adequate to answer the question it is intended to answer, i.e. whether the drug improves disease progression. This methodological aspect is a complex and contested issue in the field. What we can say is that the clinical outcome is promising.  

This study is a follow-up to one published in August 2022 that showed hints of what is seen here. Essentially, the previous study already showed that patients receiving prasinezumab (an antibody that reduces the concentration of a protein related to the pathogenesis of Parkinson's disease called alpha-synuclein) had better motor function one year after starting it than those who did not receive it. In addition, there were no relevant adverse effects. In the current study, these patients are essentially followed for up to four years, and the differences between groups receiving the drug and another group of patients not receiving the drug are not only maintained, but increased. This longer duration is key because, in a way, it is what allows us to determine that patients on the drug 'have progressed less'. 

It has some limitations: at the methodological level, the main ones are that the patients who did not receive the drug did not participate in the study, we do what we call an 'external comparison'. This implies that there may be a lot of confounding factors as this group is not well controlled. Another methodological limitation is that the evaluation is not 'blind', that is, both the doctor and the patient know whether they are receiving the drug or not, and this is already known to improve the results in the treated groups. And for me, the main limitation in terms of the potential biological effect is that the neuroimaging results measuring the dopamine circuitry (DaT-SPECT) (which is the main neurotransmitter related to Parkinson's disease) show no differences between groups. In other words, the study shows no improvement in levels of neurodegeneration. This is explainable for a number of reasons, but, if it had been positive, together with the clinical evidence, it would have represented a real milestone in the field.