Dr. Aleksandr Vagabov
MD Senior Director, Medical Affairs, Southeastern/Eastern European Markets at PTC Therapeutics
PKU is a rare genetic disorder, with autosomal recessive inheritance, resulting in elevated level of Phenylalanine (Phe) in blood, and is one of the most frequent inborn errors of metabolism (Blau, 2007). PKU prevalence varies worldwide with a global prevalence of 1:23.930 live births (Hillert, 2020). In Greece the prevalence is estimated approximately 1:10,000-12,000 births according to the Institute of Child Health.
The disruption in Phe metabolism leads to toxic accumulation of Phe in brain, and in childhood, without proper treatment, may cause irreversible mental retardation, severe intellectual disability, development delay, microcephaly, and epileptic seizures (Kaufman, 1989)3. Later in life an elevated level of Phe may lead to behavioral and psychiatric disorders, attention deficit, reduced processing speed, memory difficulties and fatigue (Mitchell, 2011).
Currently, there is no cure for PKU. The mainstay of disease management consists of prompt institution of stringent life-long Phe dietary restriction supplemented with specifically designed medical foods. The restriction in protein requires exclusion of vast sources of natural protein such as meat, fish, milk, cheese, bread, nuts, and many other common food items. Even the intake of vegetables and fruit are limited.
The success of dietary control, however, comes at a high personal cost to affected individuals and their families and the dietary restrictions lead to social difficulties and exclusions, with the potential to make people with PKU feel isolated. Consequently, life-long Phe-restricted diet is often insufficient to maintain blood Phe levels within safe limits for PKU patients (Camp 2014; Hillert 2020). The majority of PKU patients do not achieve a substantial and sustained reduction in blood Phe concentration via the restriction of dietary Phe intake alone (MacDonald 2012, Adams 2023). Compliance with a restrictive diet and Phe monitoring can be difficult for older children, adolescents, and adults (Fisch 2000, Walter 2002) and it is accepted that dietary burden does not improve with age (MacDonald 2012).
Pharmaceutical companies are trying to address the above-mentioned unmet needs in PKU, and today in Europe there are approved pharmaceutical products, which may be effective in some subgroups of PKU patients. However, still a lot of PKU patients are not responsive or not eligible for current pharmacological treatment options (Burnett, 2007, Blau 2013, Keil 2013, Hillert 2020), have strict diet limitations, and, despite being adherent to diet, are not always well controlled in terms of Phe level (MacDonald 2012, Adams 2023). PKU community strongly recognizes today the need of “new drugs that are safe, efficacious, and impacting a larger proportion of individuals with PKU “(Camp, 2014) as well as “give more freedom” in terms of diet (Rovelli, 2024).
At PTС Therapeutics*, we share the needs of the PKU community and are working to deliver an innovative therapy to address the unmet medical needs of the PKU community.
The materzal is for healthcare professionals only. Developed by PTC Therapeutics. March 2025
*PTC Therapeutics is a global pharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders.
