Update on the development of gene therapy for pku

Dietary restriction of phenylalanine has been the mainstay of treatment for over 60 years and has been highly successful, although outcomes are still suboptimal and patients can find the treatment difficult to adhere to. Pharmacological treatments are available, such as tetrahydrobiopterin, which is effective in only a minority of patients usually those with milder PKU , and pegylated phenylalanine ammonia lyase, which requires daily subcutaneous injections and causes adverse immune responses.

Publication types Research Support, N. Gov't Review. PKU is caused by mutations in the PAH gene, which is responsible for producing the enzyme that metabolizes Phe from dietary protein.

As a result, Phe accumulates to toxic levels in the blood and brain and does not convert to melanin or the amino acid tyrosine Tyr , a precursor to neurotransmitters. Since gene therapy does not integrate into the genome, it can be used in cells that are not rapidly dividing, such as an adult liver. HMI is an investigational gene therapy in clinical development for the treatment of phenylketonuria PKU in adults. HMI is an investigational, nuclease-free gene editing product candidate ultimately designed to treat pediatric patients with PKU, whose livers are rapidly dividing, following initial clinical trials in adults.

HMI is designed to express phenylalanine hydroxylase PAH and integrate into the PAH gene to restore the natural biochemical pathway that metabolizes phenylalanine Phe. PKU results in a loss of function of the enzyme phenylalanine hydroxylase PAH , which is responsible for the metabolism of phenylalanine Phe , an amino acid obtained exclusively from the diet.

Despite increased interest, enrollment is slower than anticipated due in part to COVID resurgence, and the Company anticipates providing a more detailed pheNIX update in mid when it expects to have a larger dataset. PKU is caused by mutations in the PAH gene, which is responsible for producing the enzyme that metabolizes Phe from dietary protein. As a result, Phe accumulates to toxic levels in the blood and brain and does not convert to melanin or the amino acid tyrosine Tyr , a precursor to neurotransmitters.

Homology's approach to PKU with gene therapy and gene editing candidates is designed to treat both the adult and pediatric communities with one-time treatments that address the genetic cause of PKU. Since gene therapy does not integrate into the genome, it can be used in cells that are not rapidly dividing, such as an adult liver. Gene editing is designed to make a permanent correction in cells, including those that are rapidly dividing, such as a child's liver. HMI is an investigational, nuclease-free gene editing product candidate ultimately designed to treat pediatric patients with PKU, whose livers are rapidly dividing, following initial clinical trials in adults.

HMI is designed to express phenylalanine hydroxylase PAH and integrate into the PAH gene to restore the natural biochemical pathway that metabolizes phenylalanine Phe. PKU results in a loss of function of the enzyme phenylalanine hydroxylase PAH , which is responsible for the metabolism of phenylalanine Phe , an amino acid obtained exclusively from the diet.

If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease.

The worldwide prevalence of PKU is estimated to be 50, people.