Materiały źródłowe

• #1 Phenylketonuria (PKU) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/phenylketonuria/diagnosis-treatment/drc-20376308

  Starting treatment early and continuing treatment throughout life can help prevent intellectual disability and major health problems. […] The main treatments for PKU include: A lifetime diet with very limited intake of foods with phenylalanine, Taking a PKU formula a special nutritional supplement for life to make sure that you get enough essential protein (without phenylalanine) and nutrients that are essential for growth and general health, Medications, for certain people with PKU. […] A safe amount of phenylalanine differs for each person with PKU and can vary over time. […] Your health care provider may refer you to a registered dietitian who can help you learn about the PKU diet, make adjustments to your diet when needed, and offer suggestions on ways to manage PKU diet challenges.

• #1 Phenylketonuria (PKU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17816-phenylketonuria

  Treatment for PKU is lifelong. It may include a special diet or medication. […] Treatment could include: Eating a special diet low in phenylalanine but full of nutrients. Taking vitamins, minerals and supplements. Adding a supplemental medication called sapropterin dihydrochloride (Kuvan) to break down phenylalanine in your body. […] A medication called Pegvaliase (Palynziq) allows people with PKU to eat an unrestricted diet without any supplements or Kuvan. This medication replaces the enzyme that helps to break down phenylalanine, which doesn’t work properly in PKU. […] A low-protein diet is best for people diagnosed with phenylketonuria (PKU) if they’re not treated with Pegvaliase. You should avoid foods that are high in protein, such as meat, eggs and dairy products. If you or your child has PKU, talk with your healthcare provider or a dietitian about creating a diet that is well-balanced and full of essential nutrients.

• #1 Phenylketonuria

  https://www.nhs.uk/conditions/phenylketonuria/

  If PKU is confirmed, treatment will be given straight away to reduce the risk of serious complications. Treatment includes a special diet and regular blood tests. […] The main treatment for PKU is a low-protein diet and controlled intake of many other foods, such as potatoes and cereals. […] In addition, people with PKU must take an amino acid supplement to ensure they’re getting all the nutrients required for normal growth and good health. […] If a high phenylalanine level is confirmed, a baby will immediately be started on a low-protein diet and amino acid supplements. […] A dietitian will create a detailed dietary plan for your child that can be revised as your child grows and their needs change. […] As long as a person with PKU sticks to a low-protein diet throughout childhood, and their phenylalanine levels stay within certain limits, they’ll remain well and their brain function should be unaffected.

• #1 Phenylketonuria (PKU) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/phenylketonuria/diagnosis-treatment/drc-20376308

  Because of the restricted diet, people with PKU need to get essential nutrients through a special nutritional supplement. The phenylalanine-free formula provides essential protein (amino acids) and other nutrients in a form that’s safe for people with PKU. […] The Food and Drug Administration (FDA) approved the drug sapropterin (Kuvan) for the treatment of PKU. The drug may be used in combination with a PKU diet. […] The FDA also approved a novel enzyme therapy, pegvaliase-pqpz (Palynziq), for adults with PKU when current therapy does not adequately reduce the level of phenylalanine.

• #1 What are common treatments for phenylketonuria (PKU)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  https://www.nichd.nih.gov/health/topics/pku/conditioninfo/treatments

  Following the diet is especially important during pregnancy. […] People who follow the PKU diet will not get enough essential nutrients from food. Therefore, they must drink a special formula. […] Older children and adults receive a different formula to meet their nutritional needs. This formula should be consumed every day throughout a person’s life. […] The U.S. Food and Drug Administration (FDA) has approved the drug sapropterin dihydrochloride (Kuvan) for the treatment of PKU. […] Kuvan only helps some people reduce the phenylalanine in their blood. Even if the medication helps, it will not decrease the phenylalanine to the desired amount and must be used together with the PKU diet. […] NICHD-supported researchers and other scientists are exploring additional treatments for PKU. These treatments include large neutral amino acid supplementation, which may help prevent phenylalanine from entering the brain, and enzyme replacement therapy, which uses a substance similar to the enzyme that usually breaks down phenylalanine. Researchers are also investigating the possibility of using gene therapy, which involves injecting new genes to break down phenylalanine.

• #1 New Strategies for the Treatment of Phenylketonuria (PKU)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4279156/

  Until recently, a strict low-Phe diet was the only therapy available. The PKU diet consists of are striction of natural proteins in the diet and supplementation with special medical formulas that supply vitamins, minerals, and all essential amino acids except Phe. Dietary treatment has been very effective in the prevention of impaired cognitive development, but still has its shortcomings. […] This review discusses the evolution of dietary treatment leading to improved nutritional management using an increased variety of PKU formulas, some of which containing glycomacropeptide, the introduction of new formulations of Large Neutral Amino Acid (LNAA) supplementation and pharmacological therapy with tretahydro biopterin cofactors and enzyme substitution therapy. […] Treatment of phenylketonuria is still not optimal, and so novel alternative formulas have been sought. New dietary therapies include more palatable formulas with improved caloric content allowing better compliance. Glycomacropeptide (GMP) is a naturally occurring protein derived from cheese whey, which is low in phenylalanine and an excellent source of protein for PKU patients. GMP improves the taste, variety, satiety, and convenience of the diet with consequent improved dietary compliance, metabolic control, and finally a better quality of life for patients.

• #1 New Strategies for the Treatment of Phenylketonuria (PKU)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4279156/

  Some patients with PKU respond to pharmacological doses of tetrahydropterin (BH4) with reduced blood Phe levels. At pharmacological doses, sapropterin hydrochloride acts as a molecular chaperone that promotes correct folding and stability of the PAH enzyme. […] In summary, treatment with sapropterin resulted in significant (at least 30%) and sustained reductions in blood Phe concentrations and increased dietary Phe tolerance in responsive PKU patients. […] Enzyme therapy for PKU is another option whereby the harmful increased levels of Phe can be reduced by the introduction of Phe-metabolizing enzymes changing the metabolic phenotype of PKU, regardless of genotype. […] Enzyme substitution therapy with phenylalanine ammonia-lyase (PAL) appears more promising. It can act as a surrogate for the deficient PAH and converts the excess systemic Phe to trans-cinnamic acid and ammonia.

• #1 FDA approves a new treatment for PKU, a rare and serious genetic disease | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pku-rare-and-serious-genetic-disease

  Novel enzyme therapy for adults with PKU who have uncontrolled blood phenylalanine concentrations with current treatment. […] Palynziq is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment. […] This is a novel enzyme substitution therapy that helps address a significant unmet need in PKU patients who have been unable to control their blood Phe levels with current treatment options. […] Patients treated with Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations. […] The most serious adverse reaction in the Palynziq trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment.

• #1 New Strategies for the Treatment of Phenylketonuria (PKU)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4279156/

  Overall, restriction of the intake of natural protein with supplementation of a Phe-free medical formula remains the cornerstone of PKU management and is being helped by the developments of a larger variety of medical foods, some of which made with GMP, a low-phe whey protein. […] Other novel therapeutic approaches can be categorized by the site of action or target organ. Dietary restriction of Phe intake is an example of enteral approach. Alternatively Large Neutral Amino Acid (LNAA) can be used. LNAA can compete with the same transporter of Phe across the gastrointestinal and blood brain barrier to reduce Phe absorption and entry into the brain. […] In summary, LNAA supplementation either alone or in combination with a low-Phe diet has been shown to improve health outcome for individuals unable to follow the low Phe diet. However long term outcome studies assessing efficacy and safety of LNAA supplementation are needed.

• #1 Phenylketonuria (PKU) Treatment & Management: Approach Considerations, Dietary Measures, Pharmacologic Therapy

  https://emedicine.medscape.com/article/947781-treatment

  Most patients with phenylketonuria (PKU) are treated in a specialty metabolic disease clinic, which in the United States falls under the purvue of clinical genetics. A metabolic physician and metabolic dietitian follow these patients, usually across the entire lifespan. Holistic care includes attention to growth, development, and mental health. […] Treatment consists of dietary restriction of phenylalanine often with tyrosine supplementation, usually achieved through natural protein restriction from food, with metabolic formula supplementation and ensuring sufficient essential amino acid intake. This is often referred to as 'metabolic diet’. Other essential amino acids are supplemented using various medical foods, and vitamin, mineral, and other micronutrients are followed closely. […] Phenylalanine levels are followed at regular intervals, from weekly or biweekly in younger infants, to perhaps once per month in older children and adults. Most US facilities recommend that phenylalanine levels be maintained in the range of 2 mg/dL to 6 mg/dL (120-360 mol/L). This requires expert care and close monitoring.

• #1 What are common treatments for phenylketonuria (PKU)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  https://www.nichd.nih.gov/health/topics/pku/conditioninfo/treatments

  PKU has no cure, but treatment can prevent intellectual disabilities and other health problems. A person with PKU should receive treatment at a medical center that specializes in the disorder. […] People with PKU need to follow a diet that limits foods with phenylalanine. The diet should be followed carefully and be started as soon after birth as possible. […] Experts now recommend that people with PKU stay on the diet throughout their lives for better physical and mental health. […] It is especially important for a pregnant woman with PKU to strictly follow the low-phenylalanine diet throughout pregnancy to ensure the healthy development of the infant. […] The amount of phenylalanine that is safe to consume differs for each person. Therefore, a person with PKU needs to work with a health care professional to develop an individualized diet.

• #1 Phenylketonuria

  https://www.nhs.uk/conditions/phenylketonuria/

  Provided that phenylalanine levels are strictly controlled during pregnancy, problems can be avoided and there’s no reason why a woman with PKU should not be able to have a normal, healthy baby. […] It’s recommended that all women with PKU plan their pregnancies carefully. You should aim to follow a strict low-protein diet and monitor your blood before becoming pregnant.

• #1 Phenylketonuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/phenylketonuria/

  Women with PKU who are not following a low-phenylalanine diet (and may have high levels of phenylalanine) also have higher risk of pregnancy loss. […] Lichter-Konecki U, Vockley J. Phenylketonuria: Current Treatments and Future Developments. Drugs. 2019 Apr;79(5):495-500. doi: 10.1007/s40265-019-01079-z. Citation on PubMed. […] van Wegberg AMJ, MacDonald A, Ahring K, Belanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Gizewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, van Rijn M, Trefz F, Walter JH, van Spronsen FJ. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017 Oct 12;12(1):162. doi: 10.1186/s13023-017-0685-2. Citation on PubMed.

• #1 Gene Therapy for PKU: Using Viral Vectors to Treat Phenylketonuria – American Gene Technologies

  https://www.americangene.com/pipeline/phenylketonuria-pku/

  Phenylketonuria (PKU) is caused by loss of function mutations in the gene Pah that encodes the enzyme phenylalanine hydroxylase (PAH). AGT is targeting PKU with a therapeutic strategy based on proprietary lentivirus vectors for modifying human liver to restore normal PAH activity and reduce Phe levels. […] Successful gene therapy for PKU in adults will enable treatment for infants to prevent early damage due to Phe accumulation and provide a life-long cure. […] AGT believes that LV gene therapy is the best choice for treating adults with classical PKU due to safety, durability and cost-effectiveness. Further, LV are the clear choice for PKU gene therapy in infants where the main concerns are safety and achieving life-long phenotypic correction. […] Our goal is to modify liver cells with lentivirus vectors and reconstitute the capacity for phenylalanine metabolism. […] We are committed to single-dose gene therapies that will provide permanent correction of the underlying defect in a safe and cost-effective manner. Our lentivirus vector program in PKU is designed specifically for these goals and is progressing rapidly towards clinical development.

• #1 CHOP, Penn researchers develop gene editing approaches for PKU treatment | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/chop-penn-researchers-develop-gene-editing-approaches-pku-treatment

  Phenylketonuria (PKU) is a rare newborn genetic disease that impacts between 1 in 10,000 to 1 in 20,000 people, depending on the individuals genetic ancestry. PKU causes an amino acid called phenylalanine (Phe) to build up in the bloodstream. Uncontrolled PKU can lead to intellectual disability, psychiatric issues, and seizures. While current therapies can partially improve outcomes, they require meticulous, lifelong compliance that is very difficult for most patients. […] Now, new research from the Perelman School of Medicine at the University of Pennsylvania and Childrens Hospital of Philadelphia (CHOP) provides insights into potential future treatments using gene editing specifically, two newer forms of CRISPR gene editing, prime editing and base editing. […] These findings are a significant step forward in the treatment of PKU, said Rebecca C. Ahrens-Nicklas, MD, PhD, an assistant professor of Pediatrics at Childrens Hospital of Philadelphia and a senior author of both studies. While our results with animal models point us in the right direction, future research is needed to move these advances forward. For example, next, we will focus on refining the base-editing approach and comparing its effectiveness to other gene-editing methods. […] The team of researchers recently received a $26 million grant from the National Institutes of Health to further their efforts to bring a PKU base-editing treatment to the clinic.

• #1 Genetic engineering of a PKU treatment is tested

  https://frontlinegenomics.com/genetic-engineering-of-a-pku-treatment-is-tested/

  Genetic engineering of a strain of E. Coli has successfully passed safety protocols for the treatment of PKU. […] Now, a recent multi-centre study has shown the successful genetic engineering of a strain of E. Coli Nissle 1917, designated SYNB1618, to treat the condition. […] The primary aim of these experiments was to observe the safety and patient tolerability of the engineered strain, as well as gain further insight into microbial kinetics. […] The results deemed SYNB1618 safe and well tolerated, showing only some mild to moderate adverse effects. […] Results also concluded that SYNB1618 was a safe oral treatment, available for use by patients of all ages and PAH genotypes. […] Moreover, these results warrant further study of SYNB1618 in larger cohorts of PKU patients to evaluate the reduction of plasma Phe via bacterial metabolism. […] Nonetheless, this first in-human study demonstrates huge potential in the use of genetically engineered probiotics for the treatment of rare metabolic disorders.

• #1 Phenylketonuria (PKU) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/phenylketonuria-pku

  Several medications can reduce or even eliminate the need for dietary treatment. These include: Sapropterin (Kuvan), a vitamin cofactor that helps the body break down phe. Phenylalanine ammonia lyase (PAL), a replacement enzyme that also breaks down phe. Approved in 2018 for adults with PKU, it is formulated as pegvaliase (Palynziq) and injected daily under the skin. […] The Dr. Harvey Levy Program for Phenylketonuria and Related Conditions at Boston Children’s Hospital grew out of Boston Children’s original PKU clinic, the first in the country. Today, as part of the Metabolism Program in the Division of Genetics and Genomics, we take a comprehensive approach to testing and treating children and adults with PKU, other amino acid disorders, and cofactor disorders. […] Our dedicated team of physicians, dietitians, nurse practitioners, nurse, social workers, psychologists, and biochemical genetics laboratory specialists are committed to supporting people with this highly treatable condition. PKU requires lifelong care, and our multidisciplinary team will work with you to achieve the best health available. […] We also run a special clinic, the PAL Clinic, for patients with PKU who are receiving enzyme substitution therapy.

• #1 Phenylketonuria (PKU) | Texas DSHS

  https://www.dshs.texas.gov/newborn-screening-program/newborn-screening-parent-resources/phenylketonuria-pku

  PKU cannot be cured but can be treated if a special diet is started early in the newborn period. Current research indicates that the special diet should be continued at least through adolescence and possibly throughout life. […] The special PKU diet provides all protein, calories, vitamins and minerals needed for normal growth and development. […] It is very important that the special PKU diet be carefully followed at all times. […] Successful management of PKU involves not only the parents and physician but requires the cooperation of everyone who comes in contact with the child, including relatives, neighbors, friends, babysitters, teachers, and physicians.

• #1 Phenylketonuria: a review of current and future treatments – Al Hafid – Translational Pediatrics

  https://tp.amegroups.org/article/view/8125/html

  Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. […] Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. […] There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years.

• #1 New Strategies for the Treatment of Phenylketonuria (PKU)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4279156/

  Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary treatment was found to prevent the diseases clinical features. Treatment of phenylketonuria remains difficult due to progressive decrease in adherence to diet and the presence of neurocognitive defects despite therapy. This review aims to summarize the current literature on new treatment strategies. Additions to treatment include new, more palatable foods based on glycomacropeptide that contains very limited amount of aromatic amino acids, the administration of large neutral amino acids to prevent phenylalanine entry into the brain or tetrahydropterina cofactor capable of increasing residual activity of phenylalanine hydroxylase. Moreover, human trials have recently been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylanine ammonia-lyase. Gene therapy also seems to be a promising approach in the near future.

• #1 Phenylketonuria (PKU) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/phenylketonuria-pku

  Phenylketonuria (PKU) is an inherited metabolic disorder that prevents the body from being able to break down the amino acid phenylalanine. If children born with PKU are not treated, phenylalanine in the blood can rise to levels that are harmful to the brain, interfering with brain development and causing intellectual disability. […] Fortunately, PKU is highly treatable with diet and/or medication. Following the prescribed treatment for PKU is a lifelong endeavor that requires support from family and your health care team. Children and adults who follow their treatment regimen can live full, active lives. […] PKU requires lifelong care, starting within the week or two after birth. The cornerstone of treatment is a specially prescribed diet that has very low levels of phenylalanine (phe). Because phe is found in nearly all proteins, the diet may limit or exclude meat, eggs, dairy products, legumes, and many grains. Many patients consume specially formulated low-protein foods and drink nutritional formulas.

• #2 What are common treatments for phenylketonuria (PKU)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  https://www.nichd.nih.gov/health/topics/pku/conditioninfo/treatments

  PKU has no cure, but treatment can prevent intellectual disabilities and other health problems. A person with PKU should receive treatment at a medical center that specializes in the disorder. […] People with PKU need to follow a diet that limits foods with phenylalanine. The diet should be followed carefully and be started as soon after birth as possible. […] Experts now recommend that people with PKU stay on the diet throughout their lives for better physical and mental health. […] It is especially important for a pregnant woman with PKU to strictly follow the low-phenylalanine diet throughout pregnancy to ensure the healthy development of the infant. […] The amount of phenylalanine that is safe to consume differs for each person. Therefore, a person with PKU needs to work with a health care professional to develop an individualized diet.

• #2 Phenylketonuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/phenylketonuria/

  Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. […] PKU can often be managed by following a diet that is low in phenylalanine. Since phenylalanine is found in all proteins, the PKU diet consists of avoiding meat, dairy, nuts, tofu, and other foods that are high in protein. Infants with PKU need to be fed with a low-protein formula. […] The amount of phenylalanine that is safe to consume is different for each person. Affected individuals should work with a health care professional to develop an individualized diet. […] Babies born to mothers who have PKU and are not following a low-phenylalanine diet have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth.

• #2 Phenylketonuria: Symptoms, tests, and treatment

  https://www.medicalnewstoday.com/articles/317963

  Once PKU is diagnosed in an infant, their phenylalanine levels will need to be tested weekly or more frequently until the age of one, if their medical situation requires it. […] A special PKU diet has to be followed to make sure that phenylalanine levels do not get too high. This diet includes a low-phenylalanine formula with specialized protein. In general, phenylalanine is often found in high-protein foods, so including a special low-phenylalanine formula in the diet ensures that people with PKU get enough protein. […] People with PKU will need to follow a specialized diet throughout their lives. Foods to include in the PKU diet include: fruits, vegetables, some grains, which may include low-protein cereal, bread, and pasta, low phenylalanine foods. […] A doctor managing a child’s PKU will discuss their personally-tailored diet and dietary needs, as not all children should follow the same diet.

• #2 What are common treatments for phenylketonuria (PKU)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  https://www.nichd.nih.gov/health/topics/pku/conditioninfo/treatments

  Following the diet is especially important during pregnancy. […] People who follow the PKU diet will not get enough essential nutrients from food. Therefore, they must drink a special formula. […] Older children and adults receive a different formula to meet their nutritional needs. This formula should be consumed every day throughout a person’s life. […] The U.S. Food and Drug Administration (FDA) has approved the drug sapropterin dihydrochloride (Kuvan) for the treatment of PKU. […] Kuvan only helps some people reduce the phenylalanine in their blood. Even if the medication helps, it will not decrease the phenylalanine to the desired amount and must be used together with the PKU diet. […] NICHD-supported researchers and other scientists are exploring additional treatments for PKU. These treatments include large neutral amino acid supplementation, which may help prevent phenylalanine from entering the brain, and enzyme replacement therapy, which uses a substance similar to the enzyme that usually breaks down phenylalanine. Researchers are also investigating the possibility of using gene therapy, which involves injecting new genes to break down phenylalanine.

• #2 PKU (Phenylketonuria) in your baby | March of Dimes

  https://www.marchofdimes.org/find-support/topics/birth/pku-phenylketonuria-your-baby

  Phenylketonuria (also called PKU) is a condition in which your body cant break down an amino acid called phenylalanine. Without treatment, phenylalanine builds up in the blood and causes health problems. […] If your baby has PKU, they may need testing as often as once a week or more often for the first year of life to check their phenylalanine levels. After that, they may have testing once or twice a month throughout childhood. […] Your baby needs to follow a special meal plan that is low in phenylalanine. Its best to start this meal plan as soon as possible, ideally within the first 7 to 10 days of life. […] At first, your baby gets a special protein formula that has reduced phenylalanine. […] When your baby is ready to eat solid foods, they can eat vegetables, fruits, some grains (like low-protein cereals, breads and pasta) and other low-phenylalanine foods.

• #2 Phenylketonuria – Wikipedia

  https://en.wikipedia.org/wiki/Phenylketonuria

  The amino acid tyrosine becomes essential in people with phenylalanine hydroxylase deficiency. Thus, in addition to the careful reduction of Phe in the diet, Tyr must be supplemented to ensure that nutritional needs are met. […] Supplementary „protein substitute” formulas are typically prescribed for people with PKU (starting in infancy) to provide the amino acids and other necessary nutrients that would otherwise be lacking in a low-phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary for normal brain function, is usually supplemented. […] In 2018, the FDA approved an enzyme substitute called pegvaliase which metabolizes phenylalanine. It is for adults who are poorly managed on other treatments. […] For women with PKU, it is important for the health of their children to maintain low Phe levels before and during pregnancy.

• #2 Phenylketonuria (PKU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17816-phenylketonuria

  Treatment for PKU is lifelong. It may include a special diet or medication. […] Treatment could include: Eating a special diet low in phenylalanine but full of nutrients. Taking vitamins, minerals and supplements. Adding a supplemental medication called sapropterin dihydrochloride (Kuvan) to break down phenylalanine in your body. […] A medication called Pegvaliase (Palynziq) allows people with PKU to eat an unrestricted diet without any supplements or Kuvan. This medication replaces the enzyme that helps to break down phenylalanine, which doesn’t work properly in PKU. […] A low-protein diet is best for people diagnosed with phenylketonuria (PKU) if they’re not treated with Pegvaliase. You should avoid foods that are high in protein, such as meat, eggs and dairy products. If you or your child has PKU, talk with your healthcare provider or a dietitian about creating a diet that is well-balanced and full of essential nutrients.

• #2 Current and Emerging Therapies for PKU (Including SYNB1618) | CheckRare

  https://checkrare.com/current-and-emerging-therapies-for-pku-including-synb1618/

  Jerry Vockley, MD, PhD, Head of the Division of Medical Genetics at UPMC Childrens Hospital of Pittsburgh, gives an overview of the treatment landscape for phenylketonuria (PKU), going further into detail about the mechanism of action of SYNB1618, an oral drug being investigated for treatment of this disease. […] Lifelong restriction of phenylalanine intake through the diet is needed to prevent buildup of phenylalanine in the body. However, this diet is particularly difficult to adhere to and better treatment options are needed. […] As Dr. Vockley explains, there have been a couple of drugs approved for the treatment of PKU. The first is sapropterin, a synthetic form of tetrahydrobiopterin (BH4), which is a cofactor in catabolism of phenylalanine. It acts by increasing PAH activity in patients who have residual enzyme function.

• #2 Phenylketonuria: a review of current and future treatments – Al Hafid – Translational Pediatrics

  https://tp.amegroups.org/article/view/8125/html

  Patients with PKU must strictly limit their intake of foods rich in protein, such as meats, fish, eggs and dairy products. […] Due to the stringent dietary therapy, nutritional deficiencies are common in PKU patients especially those who do not fully consume the prescribed medical food substitutes. […] The high cost of special medical foods and formula, as well as frequent visits to health professionals, pose a substantial financial burden on PKU patients and their carers. […] BH4 therapy has been successful in BH4 responsive patients; however, only about 30% of all PKU patients can benefit from this treatment. […] Treatment with the cofactor BH4 or sapropterin in BH4 responsive PKU patients has proven successful in significantly increasing Phe tolerance allowing patients to relax their diet and in some cases discontinuing the Phe free diet altogether.

• #2 Phenylketonuria (PKU) Treatment & Management: Approach Considerations, Dietary Measures, Pharmacologic Therapy

  https://emedicine.medscape.com/article/947781-treatment

  The diet should not be terminated after adolescence, because strong evidence indicates that hyperphenylalaninemia can have detrimental effects in adult patients cognitive functioning. […] Sapropterin was approved by the US Food and Drug Administration (FDA) as a treatment for PKU. It seems to be effective in a subset of patients. […] In May 2018, the FDA approved the first enzyme substitute, pegvaliase (Palynziq), to reduce phenylalanine levels in adults with PKU who have uncontrolled phenylalanine levels of more than 600 mol/L. […] Patients who have suboptimal dietary treatment may benefit to some degree from consuming large neutral amino acids, which may block phenylalanine entry into the brain and may also result in a modest lowering of plasma phenylalanine levels. […] The diet should provide adequate energy, protein, vitamin, and mineral intake. Dietary needs of phenylalanine vary during pregnancy, so weekly measurement of phenylalanine levels is important. […] Treatment at any time during pregnancy may reduce the severity of developmental delay. Women with PKU should start a phenylalanine-restricted diet before conception, and those contemplating pregnancy or who are pregnant should be treated in metabolic or PKU clinics.

• #2 Current and Emerging Therapies for PKU (Including SYNB1618) | CheckRare

  https://checkrare.com/current-and-emerging-therapies-for-pku-including-synb1618/

  The second therapy is pegvaliase (Palynziq), which is a phenylalanine ammonia lyase (PAL) enzyme that temporarily restores the levels of deficient enzyme and reduces blood phenylalanine concentrations by converting phenylalanine to ammonia and trans-cinnamic acid. This therapy has been shown to be more effective in reducing phenylalanine levels than sapropterin; however, as this therapy is administered through subcutaneous injection, often twice a day, it is a difficult therapy to use. […] SYNB1618 is an investigational oral drug being evaluated for the treatment of PKU. SYNB1618 is a genetically modified probiotic that introduces two enzymes that can metabolize phenylalanine as well as a carrier that allows the organism to take up the phenylalanine more readily. Recently interim data from the phase 2 SynPheny-1 clinical trial was presented at the International Congress of Inborn Errors of Metabolism (ICIEM) Meeting. These data show that treatment with SYNB1618 resulted in significant reductions in plasma phenylalanine levels in patients with PKU.

• #2 Phenylketonuria (PKU): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/947781-overview

  Dietary management and/or pharmacologic treatment are essential for patients with PKU. […] The mainstay of dietary management for patients with PKU consists of phenylalanine restriction which is accomplished by natural protein restriction, as well as the use of medical foods (commonly known as 'metabolic formula’) to supplement the patients intake of other essential amino acids and of vitamins and minerals. […] Sapropterin (Kuvan) is a synthetic form of BH4, the cofactor for the enzyme PAH. It may reduce phenylalanine levels or improve natural protein tolerance in patients who are deemed sapropterin-responsive, but it does not substitute the need for a metabolic diet. […] Pegvaliase (Palynziq) is a PEGylated phenylalanine ammonia lyase (PAL), which was FDA approved in May 2018. It is administered via subcutaneous injection, and exerts effect by converting phenylalanine to trans-cinnamic acid. In patients in whom it is effective, it can eliminate the need for protein restriction. […] Patients who have suboptimal dietary treatment may benefit to some degree from consuming large neutral amino acids, which may block phenylalanine entry into the brain and may also result in a modest lowering of plasma phenylalanine levels.

• #2 Adjuvant Treatment for Phenylketonuria: Future Research Needs | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/phenylketonuria-future/research

  Overall, evidence was graded as insufficient to moderate to address treatment-related questions. Dietary management remains the mainstay of treatment for PKU, and maintaining control over the lifetime is an appropriate goal. Nonetheless, there is potential to support patients in achieving their clinical goals and possibly liberalizing their diet with adjuvant therapy. BH4 has been shown in two RCTs and two open label trials to reduce Phe levels in some patients, with significantly greater reductions seen in treated versus placebo groups. Overall, harms associated with the drug were minor. […] In theory, supplementation of a Phe-restricted diet with LNAAs might have a beneficial effect on cognition as LNAAs may competitively inhibit transportation of Phe through the blood-brain barrier, thereby offering protection by potentially decreasing brain Phe levels. However, there was insufficient evidence to suggest that LNAAs could be a viable treatment option for reducing Phe levels or increasing Phe tolerance.

• #2 SciELO Brazil – Alternative Therapies for PKU Alternative Therapies for PKU

  https://www.scielo.br/j/jiems/a/P9zVNFNSxRdZ3G4BhZn9RHC/?lang=en

  In recent years, alternative treatments for PKU have been developed and their use has been suggested for some patients who become candidates for options other than traditional treatments. […] Novel therapies (BH4 and LNAA) provide more physiopathologic insight to neuropsychological symptoms and it is possible that the use will improve outcomes. […] Nevertheless, a PHE-restricted diet has proven to be efficient in all patients and remains the preferred approach for most patients.

• #2 SciELO Brazil – Alternative Therapies for PKU Alternative Therapies for PKU

  https://www.scielo.br/j/jiems/a/P9zVNFNSxRdZ3G4BhZn9RHC/?lang=en

  Tetrahydrobiopterin (BH4) is a natural cofactor of PAH. […] Sapropterindihydrochloride is a synthetic version of the naturally occurring pterin cofactor, BH4. […] Responsiveness to sapropterin varies in patients with PKU according to their clinical and molecular form. […] The role of LNAAs in brain amino acids transport was studied from 1950 but was not proposed for use as a therapy until 1994. […] Glycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide derived from cheese whey and naturally low in PHE. […] Studies in PKU mice show that GMP feeding reduces metabolic activity and attenuates immune responses due to high PHE levels. […] In patients with PKU, GMP has shown better palatability than the usual amino acid formula. […] Enzyme substitution therapy using PAL has also been suggested as a possible therapeutic approach for PKU.

• #2 Phenylketonuria: a review of current and future treatments – Al Hafid – Translational Pediatrics

  https://tp.amegroups.org/article/view/8125/html

  Large neutral amino acid supplementation has been shown to reduce cerebral Phe concentrations despite the observed increase in plasma Phe levels. […] Studies suggest that PKU patients find foods containing GMP more palatable than their usual amino acid formula, preferring a diet supplemented with GMP. […] The incorporation of GMP into low-Phe diet has improved palatability, variety and convenience of the diet and has resulted in a better control of blood Phe levels providing a more physiological form of amino acid to be consumed by PKU patients. […] Studies using gene therapy have been progressing and are still ongoing and the use of the alternative enzyme, PAL (PEGylated form) as an enzyme substitution therapy has reached phase III clinical trials, however the efficiency of the PAL reduced over time and immune reactions were elicited in some patients. […] The use of probiotics to produce and deliver the PAL enzyme has gained more attention, and studies are ongoing regarding the safety and efficacy of this approach.

• #2 Phenylketonuria

  https://www.nhs.uk/conditions/phenylketonuria/

  People with PKU must also avoid food products that contain aspartame, as it’s converted into phenylalanine in the body. […] Sapropterin is a medicine that may be used with a low-protein diet to treat a mild form of PKU called hyperphenylalaninaemia. […] If sapropterin is recommended for you, you’ll have regular blood tests to check how well it’s working. […] A child with phenylketonuria will need regular blood tests to measure levels of phenylalanine in their blood and assess how well they’re responding to treatment. […] Many adults with PKU find they function best while on a low-protein diet. The current advice is for people with PKU to remain on a low-protein diet for life. […] For women with PKU, it’s essential that they return to a strict diet if they’re considering becoming pregnant, as high phenylalanine levels can harm an unborn child.

• #2 Phenylketonuria (PKU) – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/phenylketonuria-pku

  Treatment of phenylketonuria is lifelong dietary phenylalanine restriction. […] Dietary planning and management need to be initiated in women of childbearing age before pregnancy to ensure a good outcome for the child. […] Tyrosine supplementation is increasingly used because it is an essential amino acid in patients with PKU. […] In addition, all patients with phenylalanine hydroxylase deficiency should be given a trial of sapropterin, a synthetic formulation of BH4, to determine benefit. […] For those with BH4 deficiency, treatment also includes tetrahydrobiopterin 1 to 5 mg/kg orally 3 times a day; levodopa, carbidopa, and 5-OH tryptophan; and folinic acid 10 to 20 mg orally once a day in cases of dihydropteridine reductase deficiency. […] Treatment is lifelong dietary phenylalanine restriction; adequate treatment begun in the first days of life prevents many manifestations of the disease. […] Although prognosis is excellent with treatment, frequent monitoring of plasma phenylalanine levels is required; recommended targets are between 2 mg/dL and 6 mg/dL (120 to 360 micromol/L) for all children.

• #2 Phenylketonuria

  https://www.nhs.uk/conditions/phenylketonuria/

  Provided that phenylalanine levels are strictly controlled during pregnancy, problems can be avoided and there’s no reason why a woman with PKU should not be able to have a normal, healthy baby. […] It’s recommended that all women with PKU plan their pregnancies carefully. You should aim to follow a strict low-protein diet and monitor your blood before becoming pregnant.

• #2 Phenylketonuria (PKU)

  https://www2.hse.ie/conditions/heel-prick-screening/conditions/phenylketonuria-pku/

  A dietitian will make a detailed plan for your child. This can be changed as they grow and their needs change. […] A child with PKU needs regular blood tests. This is to measure levels of phenylalanine and to see if they’re responding to treatment. […] In some cases, doctors may prescribe a medicine called sapropterin. This can help to break down phenylalanine so it will not build up in the blood. […] Many adults with PKU function best on a low-protein diet. The current advice for most is to remain on a low-protein diet for life. […] Women with PKU have to take special care during pregnancy. This is because high levels of phenylalanine can hurt an unborn baby. […] If phenylalanine levels are controlled problems can be avoided. Women with PKU are able to have normal, healthy babies. […] It’s recommended that you plan your pregnancy carefully. Follow a strict diet and check your blood twice a week before trying to become pregnant. You should try to conceive when phenylalanine levels are within the target range for pregnancy.

• #2

  https://myhealth.alberta.ca/Health/pages/conditions.aspx?hwid=hw44745

  Any woman with PKU who is planning to have a baby needs to be very careful to control her phenylalanine levels. Babies born to mothers who have high levels of phenylalanine are at risk for having a very small head, intellectual disability, growth problems, and heart problems. Having regular blood tests and following the PKU diet before and during pregnancy can help protect the baby.

• #2 New Strategies for the Treatment of Phenylketonuria (PKU)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4279156/

  Clinical trials to assess the safety and efficacy of multiple repetitive PEG-PAL injections have been performed. Subcutaneous administration of PAL-PEG was safe, well tolerated, and seemed effective at reducing blood Phe in all participants who received the highest dose. […] Another treatment under investigation involves liver repopulation with PAH-expressing cells after hepatocyte or hematopoietic stem-cell transplantation. […] Gene therapy for the treatment of PKU has been the focus of multiple research group over the last two decades. […] In conclusion, long-term outcome studies assessing efficacy and safety of GMP medical foods, BH4, LNAA supplementation and enzymatic therapy will be useful in providing the evidence allowing for standardization of management and will alternatively provide in a cost-effective way an individualized management plan for PKU patients.

• #2 Phenylketonuria (PKU) Treatment Clinical Trial | Sanofi Studies

  https://www.sanofistudies.com/clinicaltrial/312855/a-phase-1phase-2/

  PKU is an inherited disorder caused by mutations in the gene coding for the phenylalanine hydroxylase (PAH) enzyme, which increases the levels of Phenylalanine (Phe), a building block of proteins in the blood. If PKU is not adequately treated, Phe can increase to harmful levels in the body, causing injury to the brain and neuropsychological problems. The usual treatment for participants with PKU is strict dietary protein restriction along with manufactured medical foods that are low in protein and Phe. A daily oral medication and injectable medication are currently available alternative treatments. […] The purpose of the study is to evaluate the safety and efficacy of an investigational gene therapy in reducing Phe levels and in the elimination of a Phe-restricted diet. […] The investigational gene therapy is designed to insert a correct copy of the PAH gene into the liver to stimulate the liver to produce a functional PAH enzyme (a protein that breaks down Phe) to lower blood Phe levels. If this happens, then this enzyme will convert the Phe present in the blood into other essential proteins that keep the brain and nerves in the body healthy. The investigational gene therapy will be administered as a single intravenous (IV) infusion.

• #2 Phenylketonuria Program (PKU) – Children’s Hospital of Orange County

  https://choc.org/programs-services/metabolic-disorders/phenylketonuria-pku-program/

  CHOC offers a dedicated and multidisciplinary program to diagnose and treat children with phenylketonuria (PKU), an inherited disease in which the body cannot metabolize a protein called phenylalanine. […] At CHOC, children with PKU receive comprehensive and coordinated treatment by a multidisciplinary team, including board-certified biochemical physicians and endocrinologists, genetic counselors, specialized dietitians, nurses and social workers. We offer this dedicated program so that we can provide better resources to the patient and family. […] Children born with PKU will need to follow a special low-protein diet throughout their life. If they don’t, they may suffer from mood disorders, poor memory and problem-solving skills, tremors and depression. […] Phenylalanine-free formulas are available for infants. As infants start to eat solid food, their diet will need to be restricted because phenylalanine is found in many typical protein-rich foods. For example, a child with PKU should not eat milk, fish, cheese, nuts, beans or meat. Foods low in protein, such as vegetables, fruits, and some cereals, can usually be eaten in certain quantities. Specific mineral and vitamin supplements may be needed to make up for missing nutrients in the diet. […] Children and adults with PKU cannot tolerate the sugar substitute called aspartame and must read food labels to avoid sodas or any other products that contain it.

• #2 Newborn Screening Program – Phenylketonuria

  http://www.idph.state.il.us/healthwellness/fs/pku.htm

  Parents should understand that treatment is not curative and that all morbidity cannot necessarily be prevented. Long-term management, monitoring and compliance with treatment recommendations are essential to the child’s well-being. A multidisciplinary approach is recommended and should include the following specialties: pediatrics, genetics and nutrition. […] With proper medical care and lifelong dietary management, children with PKU can enjoy healthy, productive lives.

• #2 Newborn Screening Program – Phenylketonuria

  http://www.idph.state.il.us/healthwellness/fs/pku.htm

  Phenylketonuria (PKU) is a disorder of amino acid metabolism that results in excess levels of phenylalanine in body fluids. Elevated levels of phenylalanine can become neurotoxic; early detection and treatment of hyperphenylalaninemia is necessary to prevent mental retardation. […] Early diagnosis and treatment is essential to prevent developmental delays. Phenylalanine is an essential amino acid, and individuals with PKU require careful dietary management and monitoring for life. Individuals with PKU require a low phenylalanine diet, which consists of a specialized medical formula in combination with regular foods that are low in phenylalanine. […] The National Institutes of Health recommends lifetime low phenylalanine diet for individuals with PKU. […] Parents should understand that treatment is lifelong and that compliance with dietary management is imperative to the child’s health, growth and development.

• #2 New Strategies for the Treatment of Phenylketonuria (PKU)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4279156/

  Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary treatment was found to prevent the diseases clinical features. Treatment of phenylketonuria remains difficult due to progressive decrease in adherence to diet and the presence of neurocognitive defects despite therapy. This review aims to summarize the current literature on new treatment strategies. Additions to treatment include new, more palatable foods based on glycomacropeptide that contains very limited amount of aromatic amino acids, the administration of large neutral amino acids to prevent phenylalanine entry into the brain or tetrahydropterina cofactor capable of increasing residual activity of phenylalanine hydroxylase. Moreover, human trials have recently been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylanine ammonia-lyase. Gene therapy also seems to be a promising approach in the near future.

• #2 Phenylketonuria: translating research into novel therapies – Ho – Translational Pediatrics

  https://tp.amegroups.org/article/view/3542/html

  Phenylketonuria (PKU) is an inborn error of metabolism of the amino acid phenylalanine. […] The current primary treatment of PKU is the limitation of dietary protein intake, which in the long term may be associated with poor compliance in some cases and other health problems due to malnutrition. […] The only alternative therapy currently approved is the supplementation of BH4, the requisite co-factor of PAH, in the orally-available form of sapropterin dihydrochloride. […] Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents.

• #3 Phenylketonuria (PKU) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/phenylketonuria-pku

  Phenylketonuria (PKU) is an inherited metabolic disorder that prevents the body from being able to break down the amino acid phenylalanine. If children born with PKU are not treated, phenylalanine in the blood can rise to levels that are harmful to the brain, interfering with brain development and causing intellectual disability. […] Fortunately, PKU is highly treatable with diet and/or medication. Following the prescribed treatment for PKU is a lifelong endeavor that requires support from family and your health care team. Children and adults who follow their treatment regimen can live full, active lives. […] PKU requires lifelong care, starting within the week or two after birth. The cornerstone of treatment is a specially prescribed diet that has very low levels of phenylalanine (phe). Because phe is found in nearly all proteins, the diet may limit or exclude meat, eggs, dairy products, legumes, and many grains. Many patients consume specially formulated low-protein foods and drink nutritional formulas.

• #3 Phenylketonuria (PKU) Treatment & Management: Approach Considerations, Dietary Measures, Pharmacologic Therapy

  https://emedicine.medscape.com/article/947781-treatment

  Most patients with phenylketonuria (PKU) are treated in a specialty metabolic disease clinic, which in the United States falls under the purvue of clinical genetics. A metabolic physician and metabolic dietitian follow these patients, usually across the entire lifespan. Holistic care includes attention to growth, development, and mental health. […] Treatment consists of dietary restriction of phenylalanine often with tyrosine supplementation, usually achieved through natural protein restriction from food, with metabolic formula supplementation and ensuring sufficient essential amino acid intake. This is often referred to as 'metabolic diet’. Other essential amino acids are supplemented using various medical foods, and vitamin, mineral, and other micronutrients are followed closely. […] Phenylalanine levels are followed at regular intervals, from weekly or biweekly in younger infants, to perhaps once per month in older children and adults. Most US facilities recommend that phenylalanine levels be maintained in the range of 2 mg/dL to 6 mg/dL (120-360 mol/L). This requires expert care and close monitoring.

• #3 Phenylketonuria: symptoms, treatment, diagnosis and genetics | Medicover Genetics

  https://medicover-genetics.com/phenylketonuria-symptoms-treatment-diagnosis-and-genetics/

  Phenylketonuria (PKU) is an inherited, autosomal recessive condition that was first described by a Norwegian physician, Dr. Ivar Asbjorn Folling, in 1934. […] Treatment of PKU consists of maintaining phenylalanine levels within normal range through a controlled diet of food low in phenylalanine. The patient must follow this diet for life to prevent symptoms appearing. Phenylalanine is found in protein, therefore the PKU diet excludes high-protein food and contains foods low in protein, including most fruits and vegetables and other low-protein food or phenylalanine-free food preparations. […] Phenylalanine intake and levels in the body should be regularly monitored. The amount of phenylalanine that is safe for someone with PKU to consume is highly individual. […] A highly restrictive diet can cause vitamin deficiencies, and taking supplements can be beneficial; however, this should be done under supervision as vitamins, supplements and other medications may contain phenylalanine, aspartame or even milk powder. A physician can prescribe special PKU nutritional supplements.

• #3 Phenylketonuria (PKU) Treatment & Management: Approach Considerations, Dietary Measures, Pharmacologic Therapy

  https://emedicine.medscape.com/article/947781-treatment

  The diet should not be terminated after adolescence, because strong evidence indicates that hyperphenylalaninemia can have detrimental effects in adult patients cognitive functioning. […] Sapropterin was approved by the US Food and Drug Administration (FDA) as a treatment for PKU. It seems to be effective in a subset of patients. […] In May 2018, the FDA approved the first enzyme substitute, pegvaliase (Palynziq), to reduce phenylalanine levels in adults with PKU who have uncontrolled phenylalanine levels of more than 600 mol/L. […] Patients who have suboptimal dietary treatment may benefit to some degree from consuming large neutral amino acids, which may block phenylalanine entry into the brain and may also result in a modest lowering of plasma phenylalanine levels. […] The diet should provide adequate energy, protein, vitamin, and mineral intake. Dietary needs of phenylalanine vary during pregnancy, so weekly measurement of phenylalanine levels is important. […] Treatment at any time during pregnancy may reduce the severity of developmental delay. Women with PKU should start a phenylalanine-restricted diet before conception, and those contemplating pregnancy or who are pregnant should be treated in metabolic or PKU clinics.

• #3 Phenylketonuria: symptoms, treatment, diagnosis and genetics | Medicover Genetics

  https://medicover-genetics.com/phenylketonuria-symptoms-treatment-diagnosis-and-genetics/

  As long as the PKU diet is followed, people with PKU can have healthy, normal lives. […] A Food and Drug Administration (FDA)-approved drug, sapropterin, is available for the treatment of PKU, but it does not work for everyone. Patients should continue with the PKU diet while on sapropterin, although it may allow for a less restrictive diet for some people. […] The FDA has also approved a novel enzyme therapy, pegvaliase-pqpz, for adult patients with uncontrolled concentrations of phenylalanine in the blood despite current treatment. […] It is important for women with PKU to adhere to the PKU diet before and during pregnancy to reduce the risk of having high phenylalanine levels that can harm the unborn baby. A woman who adheres to the PKU diet and controls her phenylalanine levels can have a normal pregnancy and a healthy baby.

• #3 FDA approves a new treatment for PKU, a rare and serious genetic disease | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pku-rare-and-serious-genetic-disease

  Novel enzyme therapy for adults with PKU who have uncontrolled blood phenylalanine concentrations with current treatment. […] Palynziq is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment. […] This is a novel enzyme substitution therapy that helps address a significant unmet need in PKU patients who have been unable to control their blood Phe levels with current treatment options. […] Patients treated with Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations. […] The most serious adverse reaction in the Palynziq trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment.

• #3 How Does Enzyme Replacement Therapy Work for PKU?

  https://phenylketonurianews.com/2020/05/06/how-does-enzyme-replacement-therapy-work-for-pku/

  Phenylketonuria (PKU) is a rare genetic disorder characterized by abnormally high levels of phenylalanine (a protein building block, also called an amino acid) in the body. […] There is currently no cure for PKU, but treatments are available to manage symptoms and prevent disease progression. Following a low-phenylalanine diet that restricts high-protein foods may also help with symptoms. However, some patients may require enzyme replacement therapy (ERT). […] Enzyme replacement therapy is a treatment that replaces the enzyme that patients can’t make enough of themselves. In the case of PKU, this is the PAH enzyme. […] Palynziq, approved in 2018 by the U.S. Food and Drug Administration, is an enzyme replacement therapy developed by Biomarin Pharmaceutical that includes an engineered form of phenylalanine ammonia lyase — an enzyme that breaks down phenylalanine.

• #3 SciELO Brazil – Alternative Therapies for PKU Alternative Therapies for PKU

  https://www.scielo.br/j/jiems/a/P9zVNFNSxRdZ3G4BhZn9RHC/?lang=en

  Tetrahydrobiopterin (BH4) is a natural cofactor of PAH. […] Sapropterindihydrochloride is a synthetic version of the naturally occurring pterin cofactor, BH4. […] Responsiveness to sapropterin varies in patients with PKU according to their clinical and molecular form. […] The role of LNAAs in brain amino acids transport was studied from 1950 but was not proposed for use as a therapy until 1994. […] Glycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide derived from cheese whey and naturally low in PHE. […] Studies in PKU mice show that GMP feeding reduces metabolic activity and attenuates immune responses due to high PHE levels. […] In patients with PKU, GMP has shown better palatability than the usual amino acid formula. […] Enzyme substitution therapy using PAL has also been suggested as a possible therapeutic approach for PKU.

• #3

  https://myhealth.alberta.ca/Health/pages/conditions.aspx?hwid=hw44745

  Any woman with PKU who is planning to have a baby needs to be very careful to control her phenylalanine levels. Babies born to mothers who have high levels of phenylalanine are at risk for having a very small head, intellectual disability, growth problems, and heart problems. Having regular blood tests and following the PKU diet before and during pregnancy can help protect the baby.

• #3 The complete European guidelines on phenylketonuria: diagnosis and treatment | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0685-2

  Since the introduction of NBS and early treatment, patients with PKU no longer develop profound and irreversible intellectual disability. […] As there is currently no strong evidence that it is safe to discontinue dietary treatment in adults, treatment for life is recommended, even though it is acknowledged that dietary management is associated with significant patient burden. […] BH4, also known as sapropterin dihydrochloride, is used to treat a subset of PKU patients with high residual activity of the PAH enzyme. […] BH4 treatment can be given during pregnancy, but only if women are known to be BH4-responders and dietary treatment alone is unsuccessful in achieving target blood Phe control. […] The introduction of a low Phe diet may improve intellectual performance in late diagnosed PKU patients. […] Untreated PKU patients even with severe intellectual disabilities may benefit from the introduction of a low Phe diet.

• #3 CHOP, Penn researchers develop gene editing approaches for PKU treatment | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/chop-penn-researchers-develop-gene-editing-approaches-pku-treatment

  Phenylketonuria (PKU) is a rare newborn genetic disease that impacts between 1 in 10,000 to 1 in 20,000 people, depending on the individuals genetic ancestry. PKU causes an amino acid called phenylalanine (Phe) to build up in the bloodstream. Uncontrolled PKU can lead to intellectual disability, psychiatric issues, and seizures. While current therapies can partially improve outcomes, they require meticulous, lifelong compliance that is very difficult for most patients. […] Now, new research from the Perelman School of Medicine at the University of Pennsylvania and Childrens Hospital of Philadelphia (CHOP) provides insights into potential future treatments using gene editing specifically, two newer forms of CRISPR gene editing, prime editing and base editing. […] These findings are a significant step forward in the treatment of PKU, said Rebecca C. Ahrens-Nicklas, MD, PhD, an assistant professor of Pediatrics at Childrens Hospital of Philadelphia and a senior author of both studies. While our results with animal models point us in the right direction, future research is needed to move these advances forward. For example, next, we will focus on refining the base-editing approach and comparing its effectiveness to other gene-editing methods. […] The team of researchers recently received a $26 million grant from the National Institutes of Health to further their efforts to bring a PKU base-editing treatment to the clinic.

• #3 Phenylketonuria (PKU) | Lurie Children’s

  https://www.luriechildrens.org/en/specialties-conditions/phenylketonuria/

  In 2018, a new medicine called pegvaliase was FDA-approved to treat adults with PKU. It is given by daily subcutaneous injection (a shot under the skin). Pegvaliase contains an enzyme that works as a substitute for the PAH enzyme that is not working properly in patients with PKU. Response to pegvaliase varies, and it can take several months for blood Phe levels to decrease. In time, patients treated with pegvaliase may also be able to eat more protein as part of their diet. […] All forms of PKU treatment require regular blood testing to check blood Phe levels. This is very important to ensure that the treatment is keeping the Phe level in the right range for each patient. It also allows treatment adjustments to be made as needed. […] At Lurie Childrens, PKU is treated by a team of health care providers that includes a doctor or nurse practitioner, registered nurses (RNs), dietitians, a social worker and genetic counselor. The team sees more than 250 patients with PKU each year. We provide comprehensive care from the first clinic visit through the transition to adult care.

• #3 Phenylketonuria And Treatment Options – Klarity Health Library

  https://my.klarity.health/phenylketonuria-and-treatment-options/

  Education and support are crucial components of dietary management for PKU. […] Overall, dietary management plays a central role in the management of PKU and requires ongoing commitment, vigilance, and support to ensure optimal outcomes and quality of life for individuals with PKU. […] Gene Therapy Approaches are becoming quite common in attempting to cure many genetic disorders including PKU. Gene therapy holds promise as a potential curative treatment for PKU by correcting the genetic mutation responsible for the disorder. […] Clinical trials evaluating the safety and efficacy of enzyme replacement therapy for PKU are underway. […] In addition to enzyme replacement therapy and gene therapy, other emerging treatment strategies for PKU are being investigated. These include pharmacological interventions targeting alternative metabolic pathways, such as the use of BH4 analogs to enhance phenylalanine hydroxylase activity, as well as dietary supplements and nutraceuticals aimed at optimizing nutritional status and metabolic function in individuals with PKU. Medications such as sapropterin dihydrochloride (Kuvan) may be prescribed to help lower blood phenylalanine levels in some individuals with PKU.

• #3 Adjuvant Treatment for Phenylketonuria: Future Research Needs | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/phenylketonuria-future/research

  Phenylketonuria (PKU) is a metabolic disorder in which an inability to properly metabolize the amino acid phenylalanine (Phe) leads to a buildup of Phe in the blood, causing neurotoxicity and resulting in intellectual disability, delayed speech, seizures and behavior abnormalities. PKU is typically diagnosed at birth following abnormal newborn screening results. With adherence to a Phe-restricted diet, poor outcomes can be mitigated. Nonetheless, management of PKU can be difficult and onerous for the patient and the family, leading to interest in identifying new ways of managing this lifelong condition. […] The mainstay for treatment of PKU is a diet that restricts the intake of Phe to control the Phe concentration in the blood. In 2007 the United States Food and Drug Administration approved sapropterin dihydrochloride (Kuvan, formerly known as Phenoptin) for the treatment of PKU under the stipulation that studies regarding the drug’s efficacy and long-term safety continue. Sapropterin dihydrochloride (hereafter, BH4) is presumed to work by enhancing residual enzyme activity present in some individuals with PKU. In addition to a Phe-restricted diet and BH4, another potential treatment for PKU is large neutral amino acids (LNAAs). In theory, LNAAs decrease the brain Phe concentration by competing with Phe for shared amino acid transporters to cross the blood-brain barrier.

• #3 Phenylketonuria: translating research into novel therapies – Ho – Translational Pediatrics

  https://tp.amegroups.org/article/view/3542/html

  An alternative to enzyme replacement is substitution with phenylalanine ammonia lyase (PAL, EC 4.3.1.5). […] Another group of novel treatments examine how native PAH in patients can be restored to sufficient catalytic activity such that normal range blood Phe levels can be achieved. […] Another novel type of therapy of genetic disorders is the use of the nonsense read-through agents, such as the aminoglycoside antibiotic gentamicin, for treating individuals with nonsense mutations. […] Different modes of therapy for PKU are now under development.

• #3 Gene Therapy for PKU: Using Viral Vectors to Treat Phenylketonuria – American Gene Technologies

  https://www.americangene.com/pipeline/phenylketonuria-pku/

  Phenylketonuria (PKU) is caused by loss of function mutations in the gene Pah that encodes the enzyme phenylalanine hydroxylase (PAH). AGT is targeting PKU with a therapeutic strategy based on proprietary lentivirus vectors for modifying human liver to restore normal PAH activity and reduce Phe levels. […] Successful gene therapy for PKU in adults will enable treatment for infants to prevent early damage due to Phe accumulation and provide a life-long cure. […] AGT believes that LV gene therapy is the best choice for treating adults with classical PKU due to safety, durability and cost-effectiveness. Further, LV are the clear choice for PKU gene therapy in infants where the main concerns are safety and achieving life-long phenotypic correction. […] Our goal is to modify liver cells with lentivirus vectors and reconstitute the capacity for phenylalanine metabolism. […] We are committed to single-dose gene therapies that will provide permanent correction of the underlying defect in a safe and cost-effective manner. Our lentivirus vector program in PKU is designed specifically for these goals and is progressing rapidly towards clinical development.

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