- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Journal: Guide for diagnosis and treatment of hyperphenylalaninemia. (Pubmed Central) - Aug 13, 2021
If tetrahydrobiopterin-responsive hyperphenylalaninemia is diagnosed, all ages can be treated with sapropterin hydrochloride. Although there are reports that sapropterin hydrochloride is effective and safe for the prevention of maternal phenylketonuria, further investigation is required.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Clinical, Journal: Long-term preservation of intellectual functioning in sapropterin-treated infants and young children with phenylketonuria: A seven-year analysis. (Pubmed Central) - Aug 11, 2021
Sapropterin can reduce phenylalanine (Phe) levels in tetrahydrobiopterin (BH4)-responsive patients, potentially preventing the intellectual impairment caused by elevated Phe levels...All patients (n = 65) enrolled in this study experienced at least one adverse event, as expected from previous studies. In conclusion, long-term use of sapropterin in individuals with PKU helps to control blood Phe, preserve intellectual functioning, and maintain normal growth in BH4-responsive children who initiated treatment between the ages of 0 to 6 years.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Clinical, Journal: Inter- and intra-tract analysis of white matter abnormalities in individuals with early-treated phenylketonuria (PKU). (Pubmed Central) - Aug 4, 2021
Reduction in blood phe levels with the aforementioned ETPKU subsample was associated with a similar pattern of improvement (posterior-to-anterior) within most tracts. Taken together, these findings suggest that there is a systematic pattern of change in WM abnormalities in individuals with ETPKU in a posterior-to-anterior manner along individual WM tracts.
- |||||||||| Kuvan (sapropterin) / BioMarin, Daiichi Sankyo
Trial completion date, Trial primary completion date: Exercise and NO in HFrEF (clinicaltrials.gov) - Jul 6, 2021
P1, N=140, Recruiting,
Despite early delays in development, many patients can achieve independence in adult life, with usually normal neuroimaging and EEG. Trial completion date: Mar 2023 --> May 2024 | Trial primary completion date: May 2021 --> May 2023
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Retrospective data, Review, Journal: Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis. (Pubmed Central) - Jun 2, 2021
Pharmaceutical treatment with synthetic tetrahydrobiopterin (BH4), an enzyme cofactor, allows a patient subgroup to relax their diet...We propose recommendations to guide healthcare professionals when adjusting dietary prescriptions of PKU patients on BH4. Studies investigating new therapeutic options in PKU should systematically collect data on protein substitute and natural protein intakes, as well as other nutritional factors.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
[VIRTUAL] Mediation Of The Uncoupled Enos Pathway Following Oxidative Stress Using Tetrahydrobiopterin And Nitric Oxide Donor Drugs. () - May 16, 2021 - Abstract #ACSGLRM2021ACS_GLRM_92;
Nitric oxide supplementation was the main focus of this study and wastested as a stand-alone treatment and as a combined treatment along with a BH4 donordrug, sapropterin dihydrochloride. Following the two treatments, only the BAECs giventhe nitric oxide donor drug showed levels of BH4 higher than the untreated control cells.The cells treated with 25 mM nitric oxide donor drug and 2.5 mM BH4 donor drugshowed levels of BH4 that were most similar to the untreated control cells with aconcentration of approximately 27 mM BH4.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Clinical, Journal: The phenylketonuria patient: A recent dietetic therapeutic approach. (Pubmed Central) - May 13, 2021
Additions to treatment include new, more palatable foods, based on Glycomacropeptide that contains limited amounts of Phe, the administration of large neutral amino acids to prevent phenylalanine entry into the brain and tetrahydrobiopterin cofactor capable of increasing residual PAH activity...Nutritional support of PKU future mothers (maternal PKU) is also discussed. This review aims to summarize the current literature on new PKU treatment strategies.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Preclinical, Journal: Immunological impact of tetrahydrobiopterin on the central nervous system in a murine model of rabies virus infection. (Pubmed Central) - Apr 18, 2021
The immunological mediators studied in animals infected with rabies virus submitted to doses of sapropterin were Anti-RABV, IL-6, IL-2, IL-17a, INF-gamma and Anti-iNOS. It is suggested that the medication in the context of a RABV infection already installed, had the effect of modulating the inflammatory mechanisms mainly linked to the permeability of the blood-brain barrier and the migration of cytotoxic cells.
- |||||||||| NN1213 / Novo Nordisk
Phase classification, Enrollment change: Scleroderma: Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment (clinicaltrials.gov) - Apr 5, 2021
P1/2, N=12, Completed,
It is suggested that the medication in the context of a RABV infection already installed, had the effect of modulating the inflammatory mechanisms mainly linked to the permeability of the blood-brain barrier and the migration of cytotoxic cells. Phase classification: P=N/A --> P1/2 | N=32 --> 12
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Preclinical, Journal: Sapropterin reduces coronary artery malformation in offspring of pregestational diabetes mice. (Pubmed Central) - Dec 23, 2020
Sapropterin (Kuvan®) is an orally active, synthetic form of tetrahydrobiopterin (BH4) and a co-factor for eNOS with antioxidant properties...In conclusion, sapropterin treatment increases eNOS activity, reduces oxidative stress and prevents coronary artery malformation in offspring of pregestational diabetes. Sapropterin may have therapeutic potential in preventing coronary artery malformation in maternal diabetes.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Clinical, Journal: The first study of successful pregnancies in Chinese patients with Phenylketonuria. (Pubmed Central) - Dec 18, 2020
Infant outcomes were related to maternal blood Phe management prior to and during pregnancy. In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride (6R-BH) may be an option to improve the management of blood Phe levels.
- |||||||||| sapropterin / Generic mfg.
Trial completion date, Trial primary completion date: PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry (clinicaltrials.gov) - Dec 8, 2020
P=N/A, N=1927, Active, not recruiting,
In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride (6R-BH) may be an option to improve the management of blood Phe levels. Trial completion date: Sep 2023 --> Jan 2021 | Trial primary completion date: Sep 2023 --> Jan 2021
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Clinical, Journal: Does the 48-hour BH4 loading test miss responsive PKU patients? (Pubmed Central) - Nov 25, 2020
So, if blood Phe concentrations during the 48-hour BH4 test shows a clear tendency, but not sufficient decrease, a full week (with only measurements each 24 h) could be offered. A threshold of ≥20% decrease within 48 h is not useful for predicting true BH4 responsiveness.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Biomarker, Review, Journal: Tryptophan Metabolism and Related Pathways in Psychoneuroimmunology: The Impact of Nutrition and Lifestyle. (Pubmed Central) - Nov 14, 2020
A shift towards neopterin synthesis during oxidative stress may indicate a corresponding decrease in tetrahydrobiopterin, a cofactor of several mono-oxygenases, providing a further link between tryptophan metabolism and serotonergic and catecholaminergic neurotransmission. The psychoneuroimmunological consequences of tryptophan metabolism and the susceptibility of this pathway to modulation by a variety of nutritional and lifestyle-related factors have important implications for the development of both diagnostic and treatment options.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo, Vpriv (velaglucirase alfa) / Takeda, Kanuma (sebelipase alfa) / Alexion Pharma
Clinical, Journal, Orphan drug: Clinical experience with orphan drugs for rare metabolic diseases (Pubmed Central) - Nov 11, 2020
These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence.
- |||||||||| NN1213 / Novo Nordisk
Trial completion date, Trial primary completion date: NeurovEx: Neurovascular Transduction During Exercise in Chronic Kidney Disease (clinicaltrials.gov) - Nov 3, 2020
P2, N=150, Recruiting,
The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence. Trial completion date: Nov 2021 --> Sep 2022 | Trial primary completion date: Nov 2021 --> Sep 2022
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
Journal, PD(L)-1 Biomarker, IO Biomarker: Correction of Arginine Metabolism with Sepiapterin-the Precursor of Nitric Oxide Synthase Cofactor BH-Induces Immunostimulatory-shift of Breast Cancer. (Pubmed Central) - Oct 28, 2020
We tested whether supplementing sepiapterin, the precursor of tetrahydrobiopterin (BH)-the nitric oxide synthase (NOS) cofactor-redirects arginine metabolism from the pathway synthesizing polyamines to that of synthesizing nitric oxide (NO) and make breast tumors more immunogenic...Furthermore, sepiapterin abrogated the expression of a checkpoint ligand, PD-L1, in tumors in a STAT3-dependent manner. This is the first study which reveals that supplementing sepiapterin normalizes arginine metabolism, improves the immunogenicity and inhibits the growth of breast tumor cells.
- |||||||||| Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo
[VIRTUAL] Dysregulated Phenylalanine Catabolism is a Key Determinant of Cardiac Aging (OnDemand) - Oct 20, 2020 - Abstract #AHA2020AHA_5362;
Finally, we treated aged WT mice with tetrahydrobiopterin (BH4; 10 mg/kg), the essential cofactor for Phe-degrading enzyme phenylalanine hydroxylase (Pah)... Our findings established a pathogenic role for increased Phe levels in cardiac aging, highlighting modulation of Phe catabolism as a potential therapeutic target for age-associated cardiac impairment.
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