Table 2 Managing therapies for PKU
From: Genetic etiology and clinical challenges of phenylketonuria
Therapy | Delivery | Physiological mechanism | Dose |
|---|---|---|---|
Gene correction | Systemic | Delivery of base-editing to correct variants in the PAH gene | One IV |
Gene therapy | Systemic | HMI-102: provision of the normal PAH cDNA to hepatocytes (AAV, lentivirus or naked DNA) | One IV |
mRNA therapy | Systemic | Provision of lipid nanoparticle-encapsulated PAH mRNA | IV, SQ; frequency TBD |
Enzyme substitution | Systemic | RTX-134: Anabaena variabilis PAL expressed in universal @donor red blood cells | IV; frequency TBD |
| Â | Oral | SYNB1618: bacteria overexpressing PAL to metabolize Phe in the gut | Oral; three times daily |
| Â | Oral | Oral CDX-6114: PAL genetically modified to retain activity after oral administration to metabolize Phe in the gut | Oral; three times daily |
Cofactor therapy | Oral | Oral CNSA-001: sepiapterin, a precursor of tetrahydrobiopterin, to stimulate residual enzyme activity of mutant PAH | Oral; once daily |