Dojolvi (triheptanoin) / University of Queensland, Ultragenyx - LARVOL DELTA

Efficacy of Triheptanoin in Long-Chain Fatty Acid Oxidation Disorders: A Systematic Review and Meta-Analysis (SSIEM 2026) - "This effect can be explained by its anaplerotic properties, providing substrates for the TCA cycle and improving energy homeostasis. However, given the limited sample size and predominance of non-randomized studies, further large-scale, prospective studies are warranted."

Retrospective data • Review • Cardiomyopathy • Cardiovascular • Hypoglycemia • Metabolic Disorders

Fatty acid oxidation disorders detected by newborn screening: clinical, biochemical, outcomes in a single-center cohort (SSIEM 2026) - "Triheptanoin was used in two patients...Biochemical markers such as C8 and C14:1 are useful for initial risk stratification, although additional predictors are needed to better estimate disease severity and long-term outcomes. In addition to the already-known complications, neuropsychological disorders have been very common and deserve to be studied in depth."

Clinical • Cardiomyopathy • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Metabolic Disorders • Myositis

How effective can one carbon be? – a Clinical Case (SSIEM 2026) - "Although long-term neurodevelopmental outcomes remain uncertain, early use of triheptanoin may reduce metabolic crises and disease burden in severe LCHAD phenotypes Conclusion Overall, this case emphasizes the importance of early diagnosis, strict nutritional management, and timely introduction of novel therapies such as triheptanoin. A multidisciplinary approach remains crucial for optimizing outcomes and quality of life in LCHADD patients."

Clinical • Cardiomyopathy • Cardiovascular • Hepatology • Hypoglycemia • Metabolic Disorders • Retinal Disorders

Pyruvate Carboxylase Deficiency: Combination Anaplerotic and Cofactor Therapies in Presumed Type B Presentation (SSIEM 2026) - "Triheptanoin therapy was introduced (DOL 97), along with biotin and aspartic acid supplementation, resulting in rapid biochemical improvement through decreased lactate levels, improved serum bicarbonates, and markedly improved growth velocity...There were no appreciable differences in metabolic control with the implementation of thiamine, and biotin supplementation. Additional longitudinal studies are warranted to evaluate the impact of each of these therapies on biochemical stability, growth, and neurological outcomes in this rare metabolic disorder."

CNS Disorders • Developmental Disorders • Epilepsy • Metabolic Disorders • Respiratory Diseases

β-Hydroxybutyrate Formulation Performance Compared to Triheptanoin in Acadvl-/-/Acadl-/- Muscle-Double Knockout Mouse Model (SSIEM 2026) - "Discussion Our findings demonstrate that the BHB-sodium and arginine formulation outperformed triheptanoin in the MDKO mouse model. These results identify BHB as a potential new therapy for VLCAD deficiency but may be limited by the quantity required for effective treatment."

Preclinical • Cardiomyopathy • Cardiovascular • Hepatology • Hypoglycemia • Myositis • ACADVL

Bridging the Treatment Gap: A Systematic 10-Principle Framework for Drug Repurposing in Inherited Metabolic Diseases (SSIEM 2026) - " We report our experience with this framework applied in Emma CPM across several conditions: ACO2 Deficiency: Triheptanoin showed potential in restoring mitochondrial energy flux and neurologic status...MT-ATP6 & SURF1-def: Sildenafil was utilized to modulate mitochondrial biogenesis and improve clinical stabilization in Leigh syndrome spectrum disorders... The ECPM framework demonstrates that drug repurposing for IMDs is most effective when personalized biological validation meets innovative trial methodology. By prioritizing "what matters to the patient" through GAS and PROMs, we generate higher level evidence even in small patient numbers. This 10-principle systematic approach provides a scalable model for the global rare disease community to accelerate the delivery of precision therapies."

CNS Disorders • Epilepsy • Metabolic Disorders • Rare Diseases • GRIN2B

Longitudinal multimodal neuroimaging analyses in GLUT1 deficiency syndrome (SSIEM 2026) - "Methods We conducted a multimodal neuroimaging study in 14 adults with genetically confirmed GLUT1DS (7 treatment-naive and 7 receiving Triheptanoin for ≥2 years) and 14 age- and sex-matched controls...Spectroscopy analyses revealed further alterations in energy homeostasis and neurotransmission in GLUT1DS. Ongoing microstructural studies will clarify WM vulnerability and the anatomical substrates underlying cortico-striato-thalamic dysfunction in GLUT1DS, as well as impact of targeted treatment on energy metabolism."

Cardiovascular • CNS Disorders • Epilepsy • Metabolic Disorders • SLC2A1

Dual mRNA lipid nanoparticles rescue metabolic performance in a mouse model of trifunctional protein deficiency (SSIEM 2026) - "Current therapies rely on lifestyle modifications emphasizing a low-fat, high carbohydrate diet supplemented with MCT oil or triheptanoin... In cell culture, TFP-D mouse fibroblasts produce significantly elevated concentrations of long-chain acylcarnitine metabolites in MEM supplemented with palmitic acid. Initial transfections observed that endogenous M404K Hadhb acted in a dominant negative manner to prevent metabolic correction with Hadhb mRNA transfection alone (p=0.8649) but could be overcome by co-transfection of Hadhb mRNA with M404K Hadhb targeting siRNA (p<0.05) or supplemental Hadha mRNA (p<0.01). In TFP-D mice, intravenous delivery of dual mRNA LNPs significantly rescued the CTT performance by up to 71.6% compared to untreated and healthy controls (p<0.0001)."

Preclinical • Cardiomyopathy • Cardiovascular • Hepatology

N-Adipyl-D-Ala-D-His as a Superior Anaplerotic Therapy for VLCAD Deficiency in a Knockout Mouse Model (SSIEM 2026) - "AAH treatment improved running distance from ~58m to ~174m, whereas triheptanoin-treated mice running distance was similar at ~50m before and after treatment, respectively. In AAH-treated mice, pre-run blood ketones doubled from 1.3mM to 2.6mM post-run, compared to half these values in triheptanoin-treated mice, respectively. Consistent with the higher ketone levels in AAH-treated mice, hydroxybutyrylcarnitine was 0.54µM pre-run and 0.38µM post-run when compared to lower 0.14µM pre-run and 0.25µM hydroxybutyrylcarnitine post-run in triheptanoin-treated mice, respectively."

Preclinical • Cardiomyopathy • Cardiovascular • Hepatology • Hypoglycemia • Metabolic Disorders • Myositis • ACADVL

Triheptanoin treatment in severe neonatal-onset CPT II deficiency with a novel mutation: A case report (SSIEM 2026) - No abstract available

Case report • Clinical

Study of Triheptanoin for the Prevention of Hypoglycemia in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Jerry Vockley, MD, PhD | Suspended ➔ Withdrawn

Trial withdrawal • Hypoglycemia • Metabolic Disorders

Study to Evaluate the Use of Triheptanoin in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Jerry Vockley, MD, PhD | N=24 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Hypoglycemia • Metabolic Disorders

Long-term safety and efficacy of triheptanoin in Korean patients with long-chain fatty acid oxidation disorders: a prospective, open-label, single-center, phase II clinical study. (PubMed, BMC Med Genomics) - "Triheptanoin significantly reduced hospitalization burden in Korean patients with LC-FAOD and was well-tolerated, with potential benefits in physical function."

Journal • P2 data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiomyopathy • Cardiovascular • CNS Disorders • Hypoglycemia • Metabolic Disorders • Pain • Psychiatry • Retinal Disorders

Study of Triheptanoin for the Prevention of Hypoglycemia in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=8 | Suspended | Sponsor: Jerry Vockley, MD, PhD | Trial completion date: Jul 2028 ➔ Mar 2029 | Trial primary completion date: Mar 2028 ➔ Aug 2028

Trial completion date • Trial primary completion date • Hypoglycemia • Metabolic Disorders

A RARE CASE OF RHABDOMYOLYSIS LEADING TO PIGMENT NEPHROPATHY AND ACUTE KIDNEY INJURY REQUIRING HAEMODIALYSIS (ISN-WCN 2026) - "Recent studies have explored the role of triheptanoin, a specialized artificial fat substitute, in managing this disorder. Additionally, experimental pharmacological treatments such as bezafibrate and REN-01 (a PPAR-delta agonist) are being investigated for their potential in enhancing fatty acid oxidation.(10,11)Conclusion Recurrent rhabdomyolysis due to adult-onset VLCAD deficiency is uncommon but clinically significant. Identifying characteristic symptoms, particularly those linked to fasting, physical exertion, or infections, is essential for timely diagnosis. Implementing preventive measures, including appropriate lifestyle adaptations and dietary strategies, can help lower the risk of metabolic decompensation and subsequent episodes."

Clinical • Acute Kidney Injury • Cardiomyopathy • Cardiovascular • Genetic Disorders • Glomerulonephritis • Hepatology • Hypertrophic Cardiomyopathy • Hypoglycemia • Infectious Disease • Lupus Nephritis • Metabolic Disorders • Musculoskeletal Pain • Myositis • Nephrology • Renal Disease • ACADVL • MB

A novel therapy for pyridoxine-dependent epilepsy due to biallelic pathogenic variants in ALDH7A1: secondary mitochondrial energy deficiency and improvements of neurodevelopmental outcomes on triheptanoin treatment. (PubMed, Ther Adv Rare Dis) - "This novel therapy improved neurodevelopmental outcome in our patient with PDE-ALDH7A1. We think that trihepatonoin should be the part of the current standard therapy to improve neurodevelopmental outcomes in patients with PDE-ALDH7A1."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Metabolic Disorders • ALDH7A1

Study to Evaluate the Use of Triheptanoin in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Jerry Vockley, MD, PhD | Trial completion date: Dec 2027 ➔ Apr 2028 | Initiation date: Feb 2026 ➔ Jul 2026 | Trial primary completion date: Jun 2027 ➔ Dec 2027

Trial completion date • Trial initiation date • Trial primary completion date • Hypoglycemia • Metabolic Disorders

Triheptanoin for Children With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Jirair Krikor Bedoyan | Trial completion date: Jun 2027 ➔ Jun 2029 | Trial primary completion date: Dec 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • Metabolic Disorders • DLAT • PDHA1 • PDP1

Mitochondrial dysfunction in methylmalonic acidemia: A pilot study using Seahorse technology in peripheral blood. (PubMed, Mol Genet Metab Rep) - "In vitro treatments with triheptanoin, citrate, and resveratrol were performed...This exploratory study suggests that Seahorse technology can detect mitochondrial dysfunction in MMA lymphocytes. Further studies in larger cohorts are required to validate these findings and explore their clinical relevance."

Journal • Genetic Disorders • Metabolic Disorders • Ophthalmology • Renal Disease

Elamipretide Improves Mitochondrial Function in Mitochondrial Trifunctional Protein-Deficient Mice and Human Fibroblasts. (PubMed, J Inherit Metab Dis) - "Triheptanoin treatment improves most complications, but not peripheral neuropathy and retinopathy...These results support a mechanism in which elamipretide stabilizes between FAO enzymes and ETC complexes, thereby improving mitochondrial function independently of changes in cardiolipin levels. Elamipretide thus emerges as a potential therapeutic agent for TFP/LCHAD deficiency, warranting further preclinical studies."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Genetic Disorders • Hypoglycemia • Pain • Retinal Disorders

Study to Evaluate the Use of Triheptanoin in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Jerry Vockley, MD, PhD | Trial completion date: Mar 2027 ➔ Dec 2027 | Initiation date: Nov 2025 ➔ Feb 2026 | Trial primary completion date: Jan 2027 ➔ Jun 2027

Trial completion date • Trial initiation date • Trial primary completion date • Hypoglycemia • Metabolic Disorders

The Challenges of Introducing Triheptanoin in a Child with Carnitine Acylcarnitine Translocase Deficiency (CACT) (SSIEM 2023) - No abstract available

Clinical

Triheptanoin use in TANGO2-Related Disease (RD) (SSIEM 2023) - No abstract available

Lysine hyposuccinylation in human MCAD deficient fibroblast cells alleviated with heptanoic and medium branched-chain fatty acids and in Acadm-/- mice with triheptanoin (SSIEM 2023) - No abstract available

Preclinical • ACADM

Lysine hyposuccinylation in human MCAD deficient fibroblast cells alleviated with heptanoic and medium branched-chain fatty acids and in Acadm-/- mice with triheptanoin (SSIEM 2023) - No abstract available

Preclinical • ACADM