Disease modification and biomarker development in Parkinson disease: Revision or reconstruction?

A fundamental question in advancing Parkinson disease (PD) research is whether it represents one disorder or many. Does each genetic PD inform a common pathobiology or represent a unique entity? Do the similarities between genetic and idiopathic forms of PD outweigh the differences? If aggregates of α-synuclein in Lewy bodies and Lewy neurites are present in most (α-synucleinopathies), are they also etiopathogenically significant in each (α-synuclein pathogenesis)? Does it matter that postmortem studies in PD have demonstrated that mixed protein-aggregate pathology is the rule and pure α-synucleinopathy the exception? Should we continue to pursue convergent biomarkers that are representative of the diverse whole of PD or subtype-specific, divergent biomarkers, present in some but absent in most? Have clinical trials that failed to demonstrate efficacy of putative disease-modifying interventions been true failures (shortcomings of the hypotheses, which should be rejected) or false failures (shortcomings of the trials; hypotheses should be preserved)? Each of these questions reflects a nosologic struggle between the lumper’s clinicopathologic model that embraces heterogeneity of one disease and the splitter’s focus on a pathobiology-specific set of diseases. Most important, even if PD is not a single disorder, can advances in biomarkers and disease modification be revised to concentrate on pathologic commonalities in large, clinically defined populations? Or should our efforts be reconstructed to focus on smaller subgroups of patients, distinguished by well-defined molecular characteristics, regardless of their phenotypic classification? Will our clinical trial constructs be revised to target larger and earlier, possibly even prodromal, cohorts? Or should our trials efforts be reconstructed to target smaller but molecularly defined presymptomatic or postsymptomatic cohorts? At the Krembil Knowledge Gaps in Parkinson’s Disease Symposium, the tentative answers to these questions were discussed, informed by the failures and successes of the fields of breast cancer and cystic fibrosis.

Source link

WordPress database error: [Error writing file '/tmp/MY3h6Jq1' (Errcode: 28 - No space left on device)]
SELECT SQL_CALC_FOUND_ROWS wp_posts.ID FROM wp_posts LEFT JOIN wp_term_relationships ON (wp_posts.ID = wp_term_relationships.object_id) WHERE 1=1 AND wp_posts.ID NOT IN (354171) AND ( wp_term_relationships.term_taxonomy_id IN (4) ) AND wp_posts.post_type = 'post' AND (wp_posts.post_status = 'publish') GROUP BY wp_posts.ID ORDER BY RAND() LIMIT 0, 3

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy


COVID-19 (Coronavirus) is a new illness that is having a major effect on all businesses globally LIVE COVID-19 STATISTICS FOR World