Genetic Influences on Disease-Modifying Therapy Response in Multiple Sclerosis: Current Insights and Future...

Area of Science:

• Neuroimmunology
• Pharmacogenomics
• Central Nervous System Disorders

Background:

• Multiple sclerosis (MS) is a heterogeneous immune-mediated CNS disease with variable patient outcomes and treatment responses.
• Current MS treatment selection relies on clinical factors, lacking molecular predictors for disease-modifying therapies (DMTs).

Purpose of the Study:

• To critically review the pharmacogenomic literature for approved MS DMTs.
• To identify reproducible findings, limitations, and requirements for clinical translation of pharmacogenomic markers in MS.

Main Methods:

• Systematic evaluation of existing pharmacogenomic studies across various MS DMTs.
• Analysis of methodological limitations and gaps hindering clinical application.

Main Results:

• Candidate pharmacogenomic variants have been reported for MS treatments, but replication is inconsistent with modest effect sizes.
• No genetic marker is currently clinically validated for routine use in MS treatment algorithms.

Conclusions:

• Pharmacogenomics holds promise for precision medicine in MS, but significant challenges remain.
• Large, multiethnic cohorts, standardized definitions, and functional validation are crucial for integrating pharmacogenomics into MS clinical practice.