Lipodystrophy Studies

---

Advocates Andra Stratton and Sharon Halperin are raising awareness of lipodystrophy, a rare fat disorder often misdiagnosed; through global networks, they aim to improve diagnosis, access to care, and support for patients in the US and Israel.

A groundbreaking gene therapy project led by Dr. George McIlroy and Prof. Justin Rochford is gaining momentum in the fight against lipodystrophy. Selected for the prestigious Scottish Enterprise and Cell and Gene Therapy Catapult workshop, the team is working to develop a Target Product Profile (TPP) for a potential treatment that targets the root cause of this rare and debilitating condition. Their innovative approach could transform the lives of patients by restoring healthy fat tissue function and dramatically improving long-term outcomes.

Entos Pharmaceuticals has received a $4 million grant from the California Institute for Regenerative Medicine (CIRM) to advance ENTLEP001, a promising investigational gene therapy for congenital generalized lipodystrophy (CGL). ENTLEP001 aims to provide durable, redosable leptin expression using Entos’ proprietary Fusogenix™ PLV™ delivery platform. This new approach could significantly improve outcomes and reduce treatment burden compared to current therapies like metreleptin. The funding will support key preclinical activities needed to move the therapy closer to clinical trials.

Health Canada has approved Chiesi Global Rare Diseases' Myalept as an adjunct to diet for treating complications of leptin deficiency in lipodystrophy. The approval covers patients with congenital or acquired generalized lipodystrophy and familial partial lipodystrophy who haven't responded to standard treatments. Myalept, developed by Amryt Pharma and acquired by Chiesi Group, showed significant efficacy in reducing metabolic abnormalities in both generalized and partial lipodystrophy patients, with common adverse reactions including weight loss, hypoglycemia, and fatigue.

Through mouse models, researchers discovered that enhancing NRF2 expression, a transcription factor regulating various cellular pathways including oxidative stress response, in the liver can protect against lipodystrophy-induced hepatic damage. Their research, recently published in the International Journal of Molecular Sciences, demonstrates that liver-directed NRF2 targeting could offer therapeutic opportunities to mitigate the effects of lipodystrophy, potentially preventing fatty liver disease and other metabolic complications associated with the condition.

Participating in a clinical trial can lead to drug approval and new discoveries of the disease.

Some clinical trials offer compensation for participating in research. 

Discoveries made in clinical trials can reduce the burden of the disease for patients in the future. 

Feasibility of Adipose Tissue Triglyceride (TG) Labelling in Familial Partial Lipodystrophy (FPLD) 

The feasibility of adipose tissue triglyceride labeling in patients with FPLD will be assessed in this non-interventional protocol. Specifically, subjects with FPLD (n=5) and control subjects without FPLD (n=5) will undergo isotope administration followed by abdominal and femoral subcutaneous fat biopsies.

Registry for Patients With Lipodystrophy (ECLip Registry) 

The European Consortium of Lipodystrophies (ECLip), an association of European experts on lipodystrophy, has launched a registry (OSSE) for lipodystrophies which is committed to help to improve the research conditions by consolidating this kind of information in a registry. edical centers from all over the world where patients are treated with lipodystrophy are invited to join the ECLip Registry and to become ECLip Registry members. 

Natural History of Pregnancy and Pregnancy Outcomes in Metreleptin-Treated vs Untreated Subjects With Lipodystrophy 

This natural history study will collect data about the effects of taking metreleptin while pregnant. Eligibility is women aged 18 years or older with lipodystrophy who have been pregnant. Women who did and who did not take metreleptin during their pregnancies are needed. Children of women with lipodystrophy who took this drug during pregnancy are also needed.

Assess the Possibility of Diagnosing Diabetes and Rediabetes Following Oral Induced Hyperglycemia in Patients With Dunnigan's Partial Familial Lipodystrophy by Replacing 75 g of Glucose With a Standardized Carbohydrate Breakfast and Continuous Interstitial Monitoring Glucose) (HGPO-DUN) 

Dunnigan's syndrome is a partial familial lipodystrophy due to a mutation in the Lamine A LMNA gene. Clinically, patients with Dunnigan's have an absence of subcutaneous fatty tissue which mainly affects the lower part of the body and leads to severe insulin resistance responsible for early diabetes. To detect these metabolic complications as early as possible, an annual follow-up of the subjects is recommended with the performance of an OGTT test annually in non-diabetic subjects. This problem is identical for patients with cystic fibrosis leading to the same recommendation. However, whether in our experience of monitoring patients with Dunningan's lipodystrophy, in subjects at risk of diabetes or in subjects with cystic fibrosis, the OGTT test and even more so its repetition is poorly accepted, which can lead to lack of patient follow-up. An alternative solution to the OGTT is therefore justified.

Carotid Doppler Peak Velocity Variation in Liposuction Fluid Management 

This study aims to compare the hemodynamic parameters, postoperative plethysmography variability index, the total amount of postoperative intravenous fluid administration needed, and the urine output of two methods of fluid resuscitation during liposuction surgery. One method involves using carotid artery Doppler peak velocity variation, while the other is the conventional fluid ratio. The research will involve 50 female participants who have undergone liposuction and will be divided into two groups.

Evaluation of HA Dermal Fillers in the Treatment of Pathological Facial Lipoatrophy (HAtrophy) 

The study is a pilot, prospective, multicenter, proof-of-concept clinical trial that aims to evaluate the safety and efficacy of FASY F and FASY P products for the treatment of FLA.

MEASuRE: Metreleptin Effectiveness And Safety Registry (MEASuRE) 

The study is a post-authorization, prospective, voluntary registry of patients treated with commercial metreleptin including, but not limited to, patients in the US and EEA.

Study to Evaluate the Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects With PL (METRE-PL) 

This is a Phase III, double-blind, placebo-controlled, safety and efficacy study of daily SC metreleptin in subjects with Partial Lipodystrophy.

Performance and Safety of the Lipo-transfer Cannulas in Patients Underlying Lipofilling Treatment 

The purpose of this post-market clinical follow up study is to assess the safety and performance of Aesthetic Group cannulas. The study will evaluate the outcome of the Aesthetic Group cannulas range over a period of 1 month after intervention.

The Cleveland Cardiometabolic Cohort 

In this observational study, the investigators will examine the changes in body composition in HIV-infected subjects before and after initiation of HIV treatment, and look at the correlations with changes in cardiometabolic indices such as endothelial function and coronary calcium scoring.

Impact of Lipodystrophy on the Inflammatory State of Non-diabetic Dunnigan Reunion Island Subjects (LIPOKINES) 

Few data and small numbers affect the inflammatory profile of Dunnigan patients. The levels of certain pro-inflammatory biomarkers would be found higher in these subjects compared to control individuals. However, in these studies, several confounding factors were not taken into account such as smoking, an underlying chronic inflammatory disease such as diabetes and could limit the interpretation of the results. There is no other observation of the anti-inflammatory status of these patients.

Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy 

Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This can lead to health problems including diabetes. Researchers have found that the drug metreleptin improves health in people with this disease. In need of people ages 6 months and older with generalized lipodystrophy who: have received metreleptin through NIH studies AND

cannot get it through approved or compassionate use mechanisms in their home country.

Cyclophosphamide in the Treatment of Associated Acquired Lipodystrophy Syndrome With Type 1 Diabetes 

This study evaluates the change of insulin resistance and glucose metabolism of patients with panniculitis associated acquired lipodystrophy syndrome and type 1 diabetes with the treatment of cyclophosphamide.

Low Energy Diet and Familial Partial Lipodystrophy 

To evaluate the therapeutic efficacy and metabolic impact of a low energy diet (LED) in people with familial partial lipodystrophy and diabetes. Participants will be provided with a LED (total diet replacement) for 12 weeks, before the introduction of a stepped food transition. Metabolic effects will continue to be assessed for 1 year. In order to better understand why this intervention changes insulin sensitivity, we will also collect adipose and muscle tissue samples at baseline and 12 weeks into the intervention in participants willing to have these procedures performed. These samples will be used for histological, metabolite, gene expression and protein expression analyses.

Study of Cortisol Metabolism in Familial Partial Lipodystrophy Type 2 (LIPOCORT) 

Familial partial lipodystrophic syndromes are characterized by an increase in visceral adipose tissue and an atrophy of subcutaneous adipose tissue. They are associated with a severe metabolic syndrome especially when linked to the mutation of the R482 codon of the LMNA gene (Familial partial lipodystrophy type 2, FPL2). Data in lipodystrophy induced by antiretroviral therapy of HIV suggests an increase in the activity of 11β-hydroxysteroid dehydrogenase type 1 (11bHSD1). This enzyme reactivates cortisone in cortisol in adipose tissues and liver and has associated to obesity and type 2 diabetes mellitus. Hence, the hypothesis is that in patients suffering from FPL2 with the R482 codon mutation of the LMNA gene, there is an increase in the activity of HSD11B1 which could participate to the metabolic phenotype of the disease. Need patients with Familial partial lipodystrophy type 2 (FPL2) with the R482 codon mutation of the LMNA gene. 

Study of Growth Hormone Inhibition Using Pegvisomant in Severe Insulin Resistance 

The role of growth hormone (GH) in mediating pathological consequences of inadequate lipid storage will be studied in rare patient populations with high lipolysis and severe metabolic syndrome. Specifically, patients with partial lipodystrophy and pathogenic variants in the insulin receptor gene (INSR) will be studied before and after 1 month of administration of pegvisomant (a GH receptor blocker).

The LD Lync Study - Natural History Study of Lipodystrophy Syndromes  

This multicenter, collaborative, prospective, observational natural history cohort study will be conducted on approximately 500 patients with genetic or acquired lipodystrophy syndromes. Patients will be assessed on a yearly basis for approximately 5 to 7 years to collect robust clinical, metabolic, morbidity and mortality data. Medical history and patient questionnaires will be completed on a yearly basis by patients registered in the study. Clinical data such as vitals, laboratory results and anthropometric measurements will also be collected from patients' medical records if available.

Body Composition and Adipose Tissue in HIV   

Patients with HIVLD and central adiposity have been shown to have reduced GH secretion. Thus, a medication has been developed to augment GH secretion. This medication is tesamorelin. GH supplementation in other clinical settings has been shown to reduce visceral adiposity and may reduce hepatic lipid content. Need HIV-infected subjects with HIV lipodystrophy (HIVLD).