scholarly journals Regulatory news: Dojolvi (triheptanoin) as a source of calories and fatty acids in long‐chain fatty acid oxidation disorders: FDA approval summary

2021 ◽  
Author(s):  
Dina Zand ◽  
Jenny Doan ◽  
Sojeong Yi ◽  
Jie Wang ◽  
Lian Ma ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Regulatory News ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Oxidation Disorders ◽  
Fda Approval ◽  
Long Chain

scholarly journals Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10556
Author(s):  
Khaled I. Alatibi ◽  
Stefan Tholen ◽  
Zeinab Wehbe ◽  
Judith Hagenbuchner ◽  
Daniela Karall ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Oxidation Disorders ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Long Chain

Medium-chain fatty acids (mc-FAs) are currently applied in the treatment of long-chain fatty acid oxidation disorders (lc-FAOD) characterized by impaired β-oxidation. Here, we performed lipidomic and proteomic analysis in fibroblasts from patients with very long-chain acyl-CoA dehydrogenase (VLCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) deficiencies after incubation with heptanoate (C7) and octanoate (C8). Defects of β-oxidation induced striking proteomic alterations, whereas the effect of treatment with mc-FAs was minor. However, mc-FAs induced a remodeling of complex lipids. Especially C7 appeared to act protectively by restoring sphingolipid biosynthesis flux and improving the observed dysregulation of protein homeostasis in LCHADD under control conditions.

scholarly journals Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycaemic fatty acids. Fatty acid oxidation

1968 ◽  
Vol 110 (3) ◽  
pp. 511-519 ◽  
Author(s):  
A. E. Senior ◽  
B. Robson ◽  
H. S. A. Sherratt
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Saturated Fatty Acids ◽  
Chain Fatty Acid ◽  
Enoic Acid ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Cyclopropanecarboxylic Acid ◽  
Long Chain

1. The effects of the hypoglycaemic compound, pent-4-enoic acid, and of four structurally related non-hypoglycaemic compounds (pentanoic acid, pent-2-enoic acid, cyclopropanecarboxylic acid and cyclobutanecarboxylic acid), on the oxidation of saturated fatty acids by rat liver mitochondria were determined. 2. The formation of 14CO2 from [1−14C]palmitate was strongly inhibited by 0·01mm-pent-4-enoic acid. 3. The inhibition of oxygen uptake was less than that of 14CO2 formation, presumably because fumarate was used as a sparker. 4. The oxidation of [1−14C]-butyrate, -octanoate or -laurate was not strongly inhibited by 0·01mm-pent-4-enoic acid. 5. The other four non-hypoglycaemic compounds did not inhibit the oxidation of any saturated fatty acid when tested at 0·01mm concentration, though they all inhibited strongly at 10mm. 6. The oxidation of [1−14C]-myristate and -stearate, but not of [1−14C]decanoate, was strongly inhibited by 0·01mm-pent-4-enoic acid. 7. The oxidation of [1−14C]palmitate was about 50% carnitine-dependent under the experimental conditions used. 8. The percentage inhibition of [1−14C]palmitate oxidation by pent-4-enoic acid was the same whether carnitine was present or not. 9. Acetoacetate formation from saturated fatty acids was inhibited by 0·1mm-cyclopropanecarboxylic acid to a greater extent than their oxidation. 10. The other compounds tested inhibited acetoacetate formation from saturated fatty acids proportionately to the inhibition of oxidation. 11. Possible mechanisms for the inhibition of long-chain fatty acid oxidation by pent-4-enoic acid are discussed. 12. There was a correlation between the ability to inhibit long-chain fatty acid oxidation and hypoglycaemic activity in this series of compounds.

PRO47 Understanding the Burden of Long-Chain Fatty Acid Oxidation Disorders for Patients and Caregivers

2021 ◽  
Vol 24 ◽  
pp. S205
Author(s):  
E. Kruger ◽  
K. Voorhees ◽  
N.A. Thomas ◽  
M. Judge ◽  
J. Galla ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Oxidation Disorders ◽  
Long Chain

PP531 Quality Of Life Of Patients With Long-Chain Fatty Acid Oxidation Disorders Before And During Treatment With Triheptanoin

2020 ◽  
Vol 36 (S1) ◽  
pp. 41-41
Author(s):  
Eliza Kruger ◽  
Deborah Marsden ◽  
Arielle Bensimon ◽  
Erin Cook ◽  
Eli Orvis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Oxidation Disorders ◽  
Conversion Algorithm ◽  
Long Chain

IntroductionLong-chain fatty acid oxidation disorders (LC-FAOD) are a group of serious diseases in which patients are at risk of metabolic decompensation, resulting in cardiomyopathy, hypoglycemia and rhabdomyolysis and premature mortality. In addition, LC-FAOD are a burdensome disease that adversely effects quality of life (QoL) via symptoms of muscle pain, fatigue, and a difficult diet. Previous studies have reported improvements in QoL during treatment with triheptanoin as measured by short form (SF) instruments. This study sought to convert the QoL measure into a utility value for a sample of patients with LC-FAOD at baseline and 78 weeks during treatment with triheptanoin.MethodsIn an open-label Phase 2 study of triheptanoin (UX007-CL201, NCT01886378), caregivers of patients (n = 9/23 enrolled) or patients aged 18+ years (n = 6/6 enrolled) completed the SF-10 or the SF-12v2, respectively. Component summary scores at baseline and 78-week during treatment period were converted to EuroQol-Five Dimension (EQ-5D) utility (with zero representing death and 1.0 perfect health) using a published conversion algorithm (Lawrence and Fleishman 2004). Generalized linear mixed-effects models with individual-level random effects were used to estimate the utility values.ResultsAt baseline, patients’ utility was estimated to be 0.365 (standard error [SE] = 0.090) compared with 0.629 (SE = 0.072) 78-weeks during treatment, a significant improvement (p = 0.0073). In a sensitivity analysis using SF-12v2 data only (that is, only adult patients), utility estimates were 0.498 (SE = 0.084) at baseline versus 0.690 (SE = 0.068) during treatment (p = 0.0499). No patients had a major clinical event during the SF instrument recall period, indicating the benefit was driven by day-to-day improvement in QoL.ConclusionsTreatment with triheptanoin resulted in a substantial improvement in daily QoL for patients with LC-FAOD. Limitations of this study include that the estimation of utilities is from a single-arm study with small sample sizes and that the assessment of utility was based on a conversion algorithm rather than direct measurement. Nevertheless, results indicate significant improvement in QoL for patients treated with triheptanoin.

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