[Symposium] Dyslipidemia
21 Mar 2026
08:30
10:00
101
New Development in Dyslipidemia Management
Jun-Sing WangTaiwan
Moderator
Continuous Glucose Monitoring (CGM) in Asia: Behavior Change, Physician Workflow, and New Care Models
| Time | Session |
|---|---|
|
08:30
09:00
|
Kathryn TanHong Kong, China
Speaker
Lipoprotein(a): What Endocrinologists Need to KnowLipoprotein(a) [Lp(a)] is a cholesterol-rich LDL-like particle with apolipoprotein(a) covalently linked to apolipoprotein B100 via a disulfide bond. Lp(a) is synthesized within the liver and there is a general inverse correlation between Lp(a) isoform size and plasma Lp(a) concentrations. About 90% of plasma Lp(a) concentration is genetically determined and plasma levels can modestly rise after menopause in women, and in conditions like hypothyroidism, nephrotic syndrome. It has been shown that elevated Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. Although Lp(a) concentration does vary with ethnicity, relationships between Lp(a) concentration and ASCVD risk remain similar across different ethnic groups. Elevated Lp(a) is considered a cardiovascular risk-enhancing or amplification factor, and recent guidelines and consensus have increasingly recommended universal screening for Lp(a). There are as yet, no approved therapies for elevated Lp(a). Current management focuses on intensifying control of concurrent risk factors, particularly LDL-C, to reduce ASCVD risk. Amongst existing lipid-lowering drugs, only proprotein convertase subtilisin/kexin type 9 inhibitors can lower Lp(a) levels modestly. Emerging RNA-based and small-molecule therapeutics are under development and are showing promising Lp(a)-lowering effects up to 80-90%. Ongoing phase 3 cardiovascular outcomes trials will determine whether effectively lowering Lp(a) can translate to cardiovascular benefit.
101
|
|
09:00
09:30
|
Masayuki KurodaJapan
Speaker
A Novel Therapeutic Concept for Familial LCAT Deficiency: Long-Term Enzyme Replacement Using Genetically Modified AdipocytesFamilial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive disorder marked by defective HDL maturation, leading to corneal opacity, hemolytic anemia, and progressive renal dysfunction. No disease-modifying treatment has been established to date. Conventional enzyme replacement requires repeated administration with limited durability. Glybera, the first AAV1-based gene therapy for lipoprotein lipase deficiency, was withdrawn after limited clinical use and modest benefit. More broadly, in vivo AAV gene therapies face challenges including immune responses, hepatotoxicity at high vector doses, and considerable inter-patient variability in transgene expression.
Our therapeutic approach originated from studies in diabetic mouse models, where adipocytes were explored as platforms for sustained protein delivery. These cells demonstrated endocrine-like properties and long-term protein secretion in vivo. Adipocytes are particularly suited for this purpose due to their longevity, secretory capacity, and low tumorigenic risk. Building on these findings, we established an ex vivo gene and cell therapy platform using genetically modified adipocytes (GMAC), autologous adipocyte-derived cells engineered to express therapeutic proteins. As its first application, we targeted familial LCAT deficiency. These cells were expected to engraft upon subcutaneous implantation, re-differentiate into functional adipocytes, and provide long-lasting and therapeutically relevant LCAT secretion.
In a first-in-human clinical trial conducted under Japan’s regulatory framework for regenerative medicine, mature adipocytes were collected from the patient’s subcutaneous fat, converted into proliferative cells via ceiling culture, and transduced to express therapeutic human LCAT, then administered subcutaneously to the patient. Single administration of LCAT-GMAC was well tolerated with no serious adverse events. Sustained increases in serum LCAT activity were observed, accompanied by improvements in lipoprotein profiles and hemolytic anemia. A marked reduction in proteinuria was noted, and renal function remained stable throughout the follow-up period.
Remarkably, serum LCAT activity persisted for over eight years after the single administration, the longest durability ever reported for enzyme replacement. This provides the first clinical evidence that ceiling culture-derived, ex vivo modified adipocytes can achieve lasting correction of systemic enzyme deficiencies.
LCAT-GMAC therapy thus offers a potentially curative strategy for familial LCAT deficiency and a new paradigm for treating dyslipidemias and other lifelong plasma protein deficiencies.
101
|
|
09:30
10:00
|
Sung Hee ChoiSouth Korea
Speaker
Novel and Future Lipid-Lowering TherapyIn this lecture, I want to introduce the mechanism of current developing lipid lowering drugs. Small molecular inhibitors such as bempedoic acid, oral forms of newer drugs, Anti-sense oligonucleotide drugs, and siRNA technique based new lipid lowering drugs and its clinical trials. These agents target diverse pathways such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), apolipoprotein C-III (apoC-III), and Lp(a), achieving potent lipid modulation in different mechanistic approach.
101
|