Third Consensus Meeting on Neurocognitive and Functional Endpoints in MPS Clinical Studies

PROJECT SUMMARY
The mucopolysaccharidosis (MPS) disorders are a set of heterogeneous progressive, life-limiting disorders with
variable multi-system complications, including highly diverse effects on the central nervous system (CNS),
ranging from rapid neurocognitive decline, often with intense behavioral dysregulation, to mild memory issues.
While there has been an explosion in therapy development for MPSes, the ability to measure a convincing
response to therapy is complicated by the variable clinical courses across, and within, phenotypes. Incredibly
divergent clinical trial approaches internationally had hindered data comparison and raised questions as to
whether methodologies were accurately measuring cognitive and adaptive endpoints. In response, two prior
international MPS consensus conferences developed guidance for MPS trial design and implementation,
particularly for therapies targeting CNS effects. Given rapid advances in the past four years in knowledge about
treatments, disease pathology, and the patient/family experience of MPS disorders, it is critical to update the
guidance to keep pace with this surging field. The main objective of the Third Consensus Meeting on
Neurocognitive and Functional Endpoints in MPS Clinical Studies is to launch a Delphi consensus process to
modernize guidance for MPS clinical studies targeting both the CNS and multi-functional impacts of the
disorders. The specific aims are to: 1) Update recommendations for endpoint measurement of CNS impacts of
MPS across the globe; 2) Improve representation of the diverse needs of MPS disorders, broadening the set of
endpoints to be meaningful for how patients/families feel and function; 3) Mentor trainees/early stage
investigators (ESIs) on (i) identifying issues in neurocognitive and other functional endpoints and clinical trial
execution, (ii) writing literature review talks for the conference, and (iii) composing a manuscript for peer review. A
2-day, in person meeting with a diverse MPS expert panel (researchers, clinicians, advocates) and mentored
participation by trainees/ESIs will develop statements for a virtual Delphi process. The proposal's significance
is its emphasis on diversity and global representation of a broader set of functional endpoints for MPS clinical
studies. Major outcomes of this conference will be to develop modern recommendations for selection and
implementation of endpoints that are clinically meaningful to patients/families across the globe, and to enhance
career development for trainees/ESIs. This proposal's health relatedness is its potential to guide investigators
and industry in trial designs that reliably evaluate CNS response to therapy. The ultimate goal is to accelerate
the success of clinical programs for new therapies, and inclusive treatment targets, to improve the lived
experience of people touched by MPS.

Grant Number: 1R13NS145603-01
NIH Institute/Center: NIH
Principal Investigator: Heather Adams