Jun-Sing WangDr. Taiwan

• Lipoprotein(a): What Endocrinologists Need to Know
  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.
• A Novel Therapeutic Concept for Familial LCAT Deficiency: Long-Term Enzyme Replacement Using Genetically Modified Adipocytes
  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 Glybera, the first AAV1-based gene therapy for lipoprotein lipase deficiency, was withdrawn after limited clinical use and modest benefit.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.
• Novel and Future Lipid-Lowering Therapy
  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.

• Continuous Glucose Monitoring (CGM) in Asia: Behavior Change, Physician Workflow, and New Care Models
  Jun-Sing WangTaiwan Speaker Continuous Glucose Monitoring (CGM) in Asia: Behavior Change, Physician Workflow, and New Care Models
• AI and Digital Diabetes Care: Awareness, Utilisation and Perspectives from Malaysia
  Chee Keong SeeMalaysia Speaker AI and Digital Diabetes Care: Awareness, Utilisation and Perspectives from Malaysia
• Next-Generation Biomarkers for Thyroid Cancer and Endocrine Tumors
  Yen Bo LinTaiwan Speaker Next-Generation Biomarkers for Thyroid Cancer and Endocrine Tumors
• Future Endocrine Therapeutics in Southeast Asia: From Super Mono, Dual to Triple Incretin Agonists and Beyond
  Siew Hui FooMalaysia Speaker Future Endocrine Therapeutics in Southeast Asia: From Super Mono, Dual to Triple Incretin Agonists and BeyondThe role of incretin-based therapy is taking the front seat globally due to the high prevalence of obesity, diabetes and related complications worldwide. Similar scene is expected to take place in South East Asia that is facing the escalating burden of obesity driving up the already high burden of type 2 diabetes especially in the younger population despite consisting of relatively small countries in areas and population. This poses adverse socio-economic impact to the region due to increased risk of premature complications and death among the young in a region that is largely still developing. The arrival of incretin-based therapy into South East Asia since the first daily glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection in 2010 has picked up its pace in the last 5 years with the entry of weekly GLP-1 RA injection, oral GLP-1 RA and GLP-1 RA / GIP (glucose-dependent insulinotropic polypeptide) injection. This lecture will address the evidence behind its efficacy, tolerability as well as cardiovascular effects of these agents in the Asian populations. The future shift to the more potent high-dose GLP-1 receptor mono-agonist, dual, triple incretin receptor multi-agonist and beyond as these agents are approved for treatment for the twin epidemics of type 2 diabetes, obesity and related complications will be discussed along with the challenges especially on unequitable access, healthcare disparities, unregulated dispensing and the importance of a strengthened health system with multi-sectoral cooperation at the regional level to mitigate these issues.
• Discussion