Parkinson’s disease is still recognized and diagnosed by its motor symptoms, yet many of the problems that dominate daily life fall outside that definition. Sleep fragmentation, cognitive slowing, anxiety, pain, loss of motivation, autonomic dysfunction, and gastrointestinal symptoms can appear long before diagnosis, fluctuate independently of motor state, and become major determinants of independence and caregiver burden. As these symptoms are increasingly treated as therapeutic targets in their own right, the preclinical models used to study them need to keep pace.
Atuka’s new white paper, “Beyond the Canonical Motor Syndrome,” by Chief Scientific Officer Tom Johnston, PhD, sets out how Atuka approaches the route from the lived problems of people to a defensible choice of model, endpoint, and interpretation.
您将从本白皮书中获得：
- Why functional burden in PD emerges from symptoms acting together, and what a motor score misses about the effort of remaining functional
- How the order and combination of non-motor symptoms may offer clues to disease route and trajectory
- Why compensation, reserve, and challenge paradigms matter for detecting dysfunction that is concealed at rest
- A practical sequence (meaning, mechanism, model, and measure) for translating a clinical symptom into a testable construct, and the claims that disease, circuit, construct, and challenge models can each support
- Apathy as a worked example, including the construct-led tetrabenazine and AB-300 program
- A working view of development priorities across anxiety, cognition, freezing of gait, orthostatic hypotension, sleep, pain, and gastrointestinal dysfunction, with Atuka in-house data from four non-motor domains
为什么值得一读？
Drug development is beginning to treat selected non-motor symptoms as target indications, while many current models and endpoints remain weak. A model is most useful when it is judged against the specific therapeutic question it is meant to answer.
This white paper gives researchers, clinicians, and sponsors a framework for defining the function that matters to patients, identifying the circuit or physiological process a therapy is intended to alter, and choosing the model and endpoint that can test that claim with the fewest unsupported assumptions.
Download the Full White Paper to see how Atuka approaches model and endpoint selection for the non-motor and non-canonical features of Parkinson’s disease.