Dopaminergic polygenic scores and BDNF/TrkB neurotrophin biology as predictors of rehabilitation response in hypotonic cerebral palsy: a scoping review of the research gap

What the review explores.

Could dopaminergic polygenic scores and neurotrophin biology help explain rehabilitation response in hypotonic cerebral palsy?

The manuscript brings together research on dopamine-related genetics, BDNF and NGF, and the balance of TrkB receptor isoforms. It examines where evidence from other CP populations and preclinical work may suggest questions for hypotonic CP.

The author identifies a need for dedicated cohorts and descriptive biomarker data before these ideas can be evaluated for personalised rehabilitation. The review outlines eight research questions, spanning biological profiling, brain connectivity, motor learning and practical measurement.

It reports a synthesis of existing literature and a proposed research agenda. It does not present new patient data or demonstrate the efficacy of a treatment.

How it was assembled.

The manuscript describes a search of PubMed, MEDLINE and Google Scholar, supplemented by AI-assisted searches and targeted trial and sponsor searches. It follows the general principles of PRISMA-ScR.

The author screened English-language literature relevant to hypotonic or ataxic–hypotonic CP, neurotrophin biology and genetic or biological predictors of rehabilitation response. No formal risk-of-bias assessment or quantitative synthesis was performed.

Version 3 was revised following feedback on earlier drafts. The document remains a preprint without formal journal peer review.

Read the possibilities.
Understand the limits.

• Single-author review. Literature selection and interpretation may be affected by selection bias.
• Indirect evidence. Much of the discussion draws on spastic CP, acquired brain injury or preclinical studies. Its relevance to hypotonic CP remains to be tested.
• No quantitative synthesis. The review does not provide a pooled estimate of treatment benefit or a formal evidence-quality assessment.
• Time-specific trial information. Some trial details in the manuscript came from a sponsor announcement and were provisional at the time of writing.

This manuscript is not established clinical guidance and does not provide a treatment recommendation.

Use and discuss the work.

Funding: none declared. The author discloses personal experience with cerebral palsy in the manuscript.

The acknowledgements thank Dr Julie Wixey and Professor Roslyn Boyd for comments on an earlier draft. Those comments do not constitute institutional endorsement or formal journal peer review; responsibility for the content remains with the author.