Two new publications outline a transformative approach to defining, studying and treating Parkinson’s disease. Rather than approaching Parkinson’s disease as a single entity, the international cadre of researchers advocates targeting therapies to distinct “nodes or clusters” of patients based on specific symptoms or molecular features of their disease.
The findings appeared in the journals Nature Reviews Neurology and Movement Disorders.
The researchers theorize that Parkinson’s is not one disease but rather several diseases when considered from genetic and molecular perspectives. They acknowledge that viewing Parkinson’s as a single disorder that predominantly involves dopamine-neuron degeneration has been useful in the development of treatments for symptoms, such as tremor and unstable walking, that touch the vast majority of patients. At the same time, this view has yet to deliver a therapy that is effective in slowing, modifying or curing Parkinson’s. One important reason, the researchers say, could be that promising molecular therapies have been tested in large clinical trials of people who share the diagnosis of Parkinson’s, but not to the specific disease subtype most likely to benefit.
The researchers advocate a “precision medicine” approach that is rooted in systems biology, an inter-disciplinary study that focuses on the complex interactions of biological systems.
Neurologists have long observed the many faces of Parkinson’s in their patients. Some progress rapidly in their disease, some slowly. Some develop dementia relatively early, while others do not.
Tests have also revealed that patients develop deposits of alpha-synuclein, a protein, to varying degrees in the brain, colon, heart, skin, and olfactory bulb. But while these deposits have been thought to be common denominators in most individuals with Parkinson’s, they may represent byproducts of a range of biological abnormalities and may not be the best targets of therapy.
The researchers say the field must work to develop an ideal set of biomarkers. The ideal approach, they write, would start with “an assessment of biological processes” in large populations of aging individuals. The assessments would validation of a genetic variant within the protein tyrosine phostphatase receptor-type delta (PTPRD) gene.
Using autopsies from 909 individuals participating in studies of aging, the team of investigators assessed the human genome for evidence that a genetic variant could affect the neurofibrillary tangle (NFT), aggregates of the hyperphosphorylated tau protein and one of the most common forms of pathology in the aging brain. The researchers found a variant of the PTPRD gene – which is very common – contributes to the accumulation of NFT.
The researchers say that their study, taken together with previous studies in mice and flies showing a link between PTPRD and Tau pathology, suggests that altering the level of PTPRD could be an intriguing new candidate that deserves further evaluation in the search for disease therapies.
Papers: “Precision medicine for disease modification in Parkinson disease” and “Biomarker-driven phenotyping in Parkinson’s disease: A translational missing link in disease-modifying clinical trials”
Reprinted from materials provided by University of Cincinnati.