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Small chemicals could be the answer for Phenylketonuria
J Clin Invest. 2008 August 1; 118(8): 2858–2867. Published online 2008 July 1. doi: 10.1172/JCI34355
By: Angel L. Pey, Ming Ying, Nunilo Cremades, Adrian Velazquez-Campoy, Tanja Scherer, Beat Thöny, Javier Sancho, and Aurora Martinez
Find the original and full article here.
Phenylketonuria (PKU) is an inherited metabolic disorder that is characterized by a lack of ability to process the compound phenylalanine. While the detrimental effects of PKU (mental retardation, reduced head size, seizures) can be avoided by sticking to a strict diet free from phenylalanine, this diet can often be difficult and expensive to maintain. A phenylalanine-free diet prohibits all meats, dairy, and other protein-containing food, and restricts the intake of foods such as bread and other starches. The treatments that are currently available (besides the diet) mostly consist of supplements of various naturally-occurring compounds, but are generally only effective in treating a few symptoms in a small proportion of PKU patients. It is therefore important to develop other treatment options for those with PKU. Chemical genetics, or the use of small molecules to regulate and/or fix misbehaving proteins within the body, seems to be a viable option because it treats the cause (that is, dysfunctional protein) rather than just temporarily managing a symptom of this disease.
PKU is ultimately caused by harmful changes to the protein that is usually responsible for breaking down phenylalanine in healthy individuals. In this study, different small chemical compounds were tested in a few different strains of mice with PKU to see if any of the compounds could repair the damaged protein. After looking through one thousand different compounds, two chemical compounds were discovered that helped to improve the protein's function. Partially or fully restoring the function of this protein leads to a higher amount of phenylalanine processing. This means that a fuller and more relatively normal diet with meat and dairy can be consumed.
Since this study was conducted in only a few different strains of mice, it is difficult to predict just how helpful these compounds will be in humans with PKU. Additionally, these compounds are by no means a cure-all, as these compounds only fix a small set of changes that can occur to the causal protein. However, the fact that there exists compounds that can help promote protein function in strains of PKU-affected mice shows that there is potential for developing a drug that can effectively treat humans with PKU in the future. It could be only a manner of time before compounds are found that could be helpful for the protein changes that are most common in humans. These will not cure all PKU cases, but it is a great step forward to helping some individuals inflicted with PKU abandon their diet, allowing them to lead an all-but normal life.
By: Angel L. Pey, Ming Ying, Nunilo Cremades, Adrian Velazquez-Campoy, Tanja Scherer, Beat Thöny, Javier Sancho, and Aurora Martinez
Find the original and full article here.
Phenylketonuria (PKU) is an inherited metabolic disorder that is characterized by a lack of ability to process the compound phenylalanine. While the detrimental effects of PKU (mental retardation, reduced head size, seizures) can be avoided by sticking to a strict diet free from phenylalanine, this diet can often be difficult and expensive to maintain. A phenylalanine-free diet prohibits all meats, dairy, and other protein-containing food, and restricts the intake of foods such as bread and other starches. The treatments that are currently available (besides the diet) mostly consist of supplements of various naturally-occurring compounds, but are generally only effective in treating a few symptoms in a small proportion of PKU patients. It is therefore important to develop other treatment options for those with PKU. Chemical genetics, or the use of small molecules to regulate and/or fix misbehaving proteins within the body, seems to be a viable option because it treats the cause (that is, dysfunctional protein) rather than just temporarily managing a symptom of this disease.
PKU is ultimately caused by harmful changes to the protein that is usually responsible for breaking down phenylalanine in healthy individuals. In this study, different small chemical compounds were tested in a few different strains of mice with PKU to see if any of the compounds could repair the damaged protein. After looking through one thousand different compounds, two chemical compounds were discovered that helped to improve the protein's function. Partially or fully restoring the function of this protein leads to a higher amount of phenylalanine processing. This means that a fuller and more relatively normal diet with meat and dairy can be consumed.
Since this study was conducted in only a few different strains of mice, it is difficult to predict just how helpful these compounds will be in humans with PKU. Additionally, these compounds are by no means a cure-all, as these compounds only fix a small set of changes that can occur to the causal protein. However, the fact that there exists compounds that can help promote protein function in strains of PKU-affected mice shows that there is potential for developing a drug that can effectively treat humans with PKU in the future. It could be only a manner of time before compounds are found that could be helpful for the protein changes that are most common in humans. These will not cure all PKU cases, but it is a great step forward to helping some individuals inflicted with PKU abandon their diet, allowing them to lead an all-but normal life.