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

This is a multi-centre, multinational study sponsored by the pharmaceutical company F. Hoffmann-La Roche Ltd. to evaluate the efficacy of a monoclonal antibody called prasizenumab against a protein called alpha-synuclein. The accumulation of this protein in the cells causes the progressive death of dopamine-producing neurons in Parkinson's disease. 

The study was conducted in 316 Parkinson's patients, divided into three equal groups: one group received a placebo, the second group was treated with prazisenumab at a dose of 1,500mg and a third group at a higher dose (4,500mg). The antibody was administered intravenously once a month during one year of follow-up. The effect of the treatment was evaluated using the MDS-UPDRS motor scales types I, II and III, expecting an improvement in the typical motor symptoms of the disease. Only a slight improvement on the MDS-UPDRS type III scale was observed in the group of patients who had a faster disease progression, with an improvement of approximately 5 points on this scale (an improvement of more than 4.63 points was considered a positive result). 

In neurodegenerative diseases, the accumulation of misfolded proteins is typically observed in the brain, specifically alpha-synuclein within dopamine-producing cells, and other proteins such as tau (intracellular) or amyloid (extracellular) in the case of Alzheimer's disease. This new generation of monoclonal antibodies attempts to dissolve the accumulations of these misfolded proteins to ameliorate the progression of these diseases, and are currently causing heated controversy. All of them are administered intravenously and their penetration into the brain is very low (less than 1%). Moreover, once in the brain, it remains to be seen whether the antibodies are able to enter the neurons that accumulate these proteins in order to exert their effect. In the case of aducanumab and lecanemab (to treat Alzheimer's disease), the target is the amyloid protein (extracellular). Both antibodies have a number of very important side effects that need to be taken into account when considering their administration, especially oedema and brain haemorrhages (present in more than 40% of patients treated with these antibodies 

Although the studies published to date with monoclonal antibodies against alpha-synuclein, specifically prasizenumab (PASADENA study) and cinpanemab (SPARK study) have not reported adverse effects, it is clear that for the moment that the improvement obtained is very small, with a follow-up time of only one year. It is really difficult to predict the outcome of this type of treatment over a longer period of time, as it is completely unknown. 

Another aspect to take into account before considering these new drugs for Parkinson’s patients is their high price. In the case of the monoclonal antibodies against the amyloid protein for the treatment of Alzheimer's (aducanumab and lecanemab), their price in the United States is approximately US $26,500, 80% of which is covered by Medicare. For the patient, this means an annual cost of just over 5,000 dollars, which has important social implications for access to this medication by racial minorities such as African-American and Hispanic communities. In the EU, this cost is high and will have to be covered by national health systems. 

In summary, longer-term trials will be needed in which potential benefits are measured using other parameters in addition to motor scales. Besides, the balance between cost, benefit and potential adverse effects needs to be carefully weighed before such treatments are given to Parkinson’s patients. Finally, it will be necessary to have a new generation of antibodies designed to increase their penetration into target neurons or to combine their administration with other techniques that are already available today, such as the permeabilisation of the blood-brain barrier using high-intensity focused ultrasound (HIFU technique).