NIH, AlphaRose study advances personalised therapy approach for rare genetic disorder

Researchers identify patient-specific drug candidates for Sanfilippo syndrome type B, highlighting the potential of precision drug repurposing for rare diseases

AlphaRose Therapeutics, through its drug discovery division RareLabs, and researchers from the National Center for Advancing Translational Sciences (NCATS) at the US National Institutes of Health (NIH) have published a study demonstrating a personalised drug repurposing platform capable of identifying treatments tailored to an individual patient's genetic profile.

Published in the Journal of Personalized Medicine, the study, titled "Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB," introduces a scalable "N-of-1" precision medicine approach for rare genetic disorders.

The research focuses on Sanfilippo syndrome type B (MPS IIIB), a rare, progressive lysosomal storage disorder caused by mutations in the NAGLU gene. The disease currently has no approved treatment, and the presence of more than 300 known disease-causing mutations has complicated efforts to develop a universal therapy.

Using the NCATS Pharmaceutical Collection, a library of 2,807 clinically approved compounds, researchers developed a high-content imaging platform based on patient-derived skin cells to identify therapies for an individual patient.

The screening identified four orally available approved medicines—baclofen, dextrose, epalrestat and moxifloxacin—that significantly corrected lysosomal defects in cells from the index patient.

 However, when the same drugs were evaluated in cells from another patient carrying a different NAGLU mutation, none demonstrated therapeutic benefit. According to the researchers, this finding highlights the strong influence of genetic variation on treatment response and underscores the need for mutation-specific therapeutic strategies in MPS IIIB.

 The study suggests that patients with different genetic mutations may require individually tailored therapies rather than a one-size-fits-all approach, providing further evidence for the growing role of precision medicine in rare disease treatment.

 "Our goal is to prove that precision treatments are not just a concept, but a viable, repeatable path for underserved patient communities. I am grateful for the NIH NCATS team, and this is just the beginning of what will come from our collaboration. Every life matters!" said Rodney A. Bowling Jr., Chief Scientific Officer, AlphaRose RareLabs, and co-author of the study.

 The researchers believe the platform could be adapted for other rare genetic disorders, potentially accelerating the identification of personalised therapies by repurposing existing medicines and reducing the time and cost associated with conventional drug development.