Skeletal muscle dysfunction is a frequent and clinically relevant systemic manifestation of Chronic Pulmonary Obstructive Disease (COPD), which is still poorly understood. Therefore, the focus of this study is on the role of a deficit in tetrahydrobiopterin and nitric oxide synthase uncoupling induced by chronic oxidative stress on metabolic and vascular abnormalities in skeletal muscle of patients suffering from COPD.

开始日期2021-04-01

申办/合作机构

University of Massachusetts Amherst

NCT03519711 / Completed临床1/2期

A Phase 1/2, Open-Label, Randomized Parallel Arm, Intra-patient Dose Escalation Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of CNSA-001(Sepiapterin) in Primary Tetrahydrobiopterin Deficient Patients With Hyperphenylalaninemia

This study has been designed to demonstrate the safety, pharmacokinetics (PK) and preliminary efficacy of PTC923 (CNSA-001) in reducing blood phenylalanine concentrations in participants with hyperphenylalaninemia due to primary BH4 deficiency (PBD).

开始日期2019-01-03

申办/合作机构

PTC Therapeutics, Inc.

100 项与四氢生物蝶呤缺乏症相关的临床结果

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100 项与四氢生物蝶呤缺乏症相关的转化医学

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0 项与四氢生物蝶呤缺乏症相关的专利（医药）

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项与四氢生物蝶呤缺乏症相关的文献（医药）

2024-01-01·BMJ Case Reports

Evaluation of catatonia in autism and severe depression revealing Phelan-McDermid syndrome and tetrahydrobiopterin deficiency

Article

作者: Pierri, Joseph ; Finegold, David ; Pan, Lisa ; Boley, Georgia

The authors describe a female in her late twenties, presenting with catatonia and diagnosed with epilepsy, autism spectrum disorder, mild intellectual disability, psychosis, dysthymia, anxiety and bipolar disorder, receiving weekly electroconvulsive therapy (ECT). After testing, findings indicated an interstitial deletion in the 22q13.33 region associated with Phelan-McDermid syndrome. In addition, the patient had low cerebral spinal fluid tetrahydrobiopterin (BH4) levels, suggesting dysfunction in the pterin biosynthetic pathway. As a result, the patient started on sapropterin, a BH4replacement small molecule. After sapropterin treatment, catatonia improved, and the need for ECT decreased. There was an improvement in her cognitive ability, attention and independence. However, there has been no improvement in seizure frequency.

2018-09-01·Journal of Inherited Metabolic Disease2区 · 医学

Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders

2区 · 医学

Article

作者: Krzywińska-Zdeb, E ; Scholl-Bürgi, S ; Knerr, I ; Bruggemann, N ; Kuseyri, O ; Monavari, A A ; Opladen, T ; Yapıcı, Z ; Romanowska, H ; Giżewska, M ; Klein, C ; Karall, D ; Leuzzi, V ; Weissbach, A

AbstractIntroductionInborn errors of tetrahydrobiopterin (BH4) biosynthesis or recycling are a group of very rare neurometabolic diseases. Following growing awareness and improved availability of drug treatment the number of patients with BH4 disorders reaching adulthood is constantly increasing. Pregnancy care of patients with these disorders is therefore a new challenge for clinicians.MethodsThis retrospective study summarises for the first time clinical and biochemical monitoring data of 16 pregnancies in seven women with different disorders of BH4 metabolism and evaluates treatment regimens before and during pregnancy in relation to the obstetrical outcome and paediatric follow‐up.ResultsWorsening of pre‐existing neurological symptoms or occurrence of new symptoms during pregnancy was not observed in most of the cases. Treatment regimens remained mostly unchanged. Pregnancies were not complicated by disease‐specific features. Organ abnormalities, miscarriage, prematurity, IUGR and chromosomal changes were occasionally reported, without showing any association with the standard drug treatment for BH4 deficiencies.ConclusionAlthough our data on 16 pregnancies in seven patients did not present any association of standard drug treatment with an increased rate of pregnancy complications, abnormal obstetrical or paediatric outcome, an intensive clinical and biochemical supervision by a multidisciplinary team before, during and after the pregnancy in any BH4 deficiency is essential since available data on pregnancies in patients with BH4 deficiencies is limited.

2009-10-01·Medical Hypotheses4区 · 医学

Do sauna therapy and exercise act by raising the availability of tetrahydrobiopterin?

4区 · 医学

Article

作者: Pall, Martin L

Sauna therapy has been used to treat a number of different diseases known or thought to have a tetrahydrobiopterin (BH4) deficiency. It has been interpreted to act in multiple chemical sensitivity by increasing chemical detoxification and excretion but there is no evidence that this is its main mode of action. Sauna therapy may act to increase BH4 availability via two distinct pathways. Increased blood flow in heated surface tissues leads to increased vascular shear stress, inducing increased activity of GTP cyclohydrolase I (GTPCH-I) in those vascular tissues which will lead to increasing BH4 synthesis. A second mechanism involves the heat shock protein Hsp90, which is induced by even modest heating of mammalian tissues. Sauna heating of these surface tissues may act via Hsp90, which interacts with the GTPCH-I complex and is reported to produce increased GTPCH-I activity by lowering its degradation. The increased consequent availability of BH4 may lead to lowered nitric oxide synthase uncoupling, such as has been reported for the eNOS enzyme. Increased BH4 synthesis in surface tissues of the body will produce increased circulating BH4 which will feed BH4 to other body tissues that may have been BH4 deficient. Similar mechanisms may act in vigorous exercise due to the increased blood shear stresses and possibly also heating of the exercising tissues and heart. There is a large and rapidly increasing number of diseases that are associated with BH4 depletion and these may be candidates for sauna therapy. Such diseases as hypertension, vascular endothelial dysfunction, multiple chemical sensitivity and heart failure are thought to be helped by sauna therapy and chronic fatigue syndrome and fibromyalgia may also be helped and there are others that may be good candidates for sauna therapy.