Preclinical Findings for Phenylketonuria and Metachromatic Leukodystrophy Gene Therapies Look Promising

According to a story from BioSpace, the genetic medicines company Homology Medicines, Inc., has recently released preclinical data supporting the development of two experimental gene therapies. One, called HMI-202, is in development as a treatment for metachromatic leukodystrophy (MLD). The other is called HMI-102 and is being developed to treat phenylketonuria (PKU). The data was presented at the 2019 meeting of The American Society of Human Genetics.

About Phenylketonuria

Phenylketonuria (PKU) is a type of metabolic disorder affecting the enzyme phenylalanine, which builds up in the body and can cause serious problems. Prompt treatment is essential to avoid major complications. Symptoms of phenylketonuria include small head size, low birth weight, an unusual musty odor, pale skin, behavioral problems, intellectual disability, heart issues, seizures, and mental disorders. The primary management strategy is a highly controlled diet that is low in phenylalanine. Most patients eventually go off the diet when they reach adulthood. To learn more about phenylketonuria, click here.

About Metachromatic Leukodystrophy

Metachromatic leukodystrophy is a lysosomal storage disease and variant of leukodystrophy which is linked to a genetic mutation that prevents the regular production of an enzyme called arylsulfatase A (ARSA), which results in the destruction of the myelin sheath, a fatty, insulating protective layer that is critical for neuronal function. Symptoms vary depending on when they appear but can include muscle stiffness, wasting, and weakness, vision loss, developmental delays, paralysis, dementia, problems swallowing, and more. While bone marrow transplant can help some patients, the disease is ultimately fatal. To learn more about metachromatic leukodystrophy, click here.

Preclinical Study Findings

Administration of HMI-102 in a mouse model of phenylketonuria resulted in normalized levels of Phe for a 48 week period. The appearance of biochemical metabolites were further indication that the metabolic pathway was functioning normally. The treatment also appeared to be safe with no adverse toxicity findings even at the highest dose level.

Administration of HMI-202 in a mouse model of metachromatic leukodystrophy saw an increase in ARSA enzyme to therapeutic levels. The therapy was able to modulate several disease-related biomarkers for the 48 week duration of the study. Researchers also confirmed the ability of the therapy to cross the blood-brain and blood-nerve-barriers.

These findings will give Homology a solid foundation of data as they continue to test these experimental gene therapies going forward.


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