An earlier trial, NCT02157714, showed that the therapy lowered blood levels of alpha-synuclein, a protein found in abundance in the human brain, by almost ninety-seven percent after one injection.
Researchers do not fully understand all aspects of alpha-synuclein. However, it has been shown that the protein releases dopamine which affects voluntary and involuntary movement in those with Parkinson’s.
Prasinezumab’s ability to reduce alpha-synuclein is evidence of its potential to slow the neurodegeneration that is associated with the toxic accumulation of the protein.
Part 2 of Phase II Clinical Trial
Three hundred sixteen early-stage Parkinson’s patients were enrolled in PASADENA (NCT03100149) Phase II, parts 1 and 2. Sixty-five clinical sites across Europe were represented.
Younger patients treated with MAO-B inhibitors were included, thus expanding the type of patients represented. Monoamine oxidase is an enzyme known to remove neurotransmitters such as serotonin and dopamine from the brain. MAO inhibitors, one of the earliest antidepressants now used to treat Parkinson’s, acts against these enzymes.
The primary endpoint of PASADENA was to determine whether the drug had an effect on either motor or non-motor symptoms.
The secondary goals were to evaluate the effectiveness and safety of prasinezumab.
Brain imaging tools were utilized in order to gauge the level of dopamine-producing neurons in the brain.
Parkinson’s disease involves clusters of alpha-synuclein that accumulate in the central nervous system resulting in worsening motor or non-motor symptoms.
Approximately ten million people worldwide are affected with the Parkinson’s. The disease is second to Alzheimer’s as an age-related degenerative neurological disorder. Parkinson’s affects forty-one people per one hundred thousand, mostly over the age of sixty.
Currently, available treatments for the disease address symptoms rather than the disease itself. Therefore, the patient’s debilitating side effects will get progressively worse.
Alpha-synuclein, found in abundance in the brain, is generally concentrated near the ends of nerve cells. The toxic clusters or clumps of alpha-synuclein are called amyloid.
Researchers agree that amyloid contribute to the onset and progression of Parkinson’s. There is also evidence that the toxic clusters spread to neurons causing the spread of the disease.
Prasinezumab (PRX002) is a protein created in the lab that binds to a substance in the body(monoclonal). Roche collaborated with Prothena in the development of the drug.
PRX002 selectively binds to the alpha-synuclein clusters causing an immune response.
Researchers for the PASADENA trial noted that the trial’s participants are representative of the general Parkinson’s population and therefore suitable for evaluation of the effect of therapies on disease progression.