Mitochondrial Function in Transthyretin Amyloidosis (MIT-Amylose)

University Hospital Center of Martinique

Status: Terminated

Conditions: Cardiac Amyloidosis

Study type: Observational

Funder types: Other

Identifiers

NCT03328338

16/E/17

Details and patient eligibility

About

Hereditary (familial) amyloidosis arising from the misfolding of a mutated or variant transthyretin, is the most frequent form of amyloid cardiomyopathy in the Caribbean basin. Affected organs invariably harbor extracellular amyloid deposits in the myocardium. Circulating or pre-fibrillar amyloidogenic proteins are implicated in the disruption of cell function. The investigators aim is to demonstrate that transthyretin mediated amyloid disease alter the mitochondrial function of cardiac cells.

Full description

Systemic amyloidosis are a family of diseases induced by misfolded and/or misassembled proteins. Extracellular deposits of these proteins disrupt vital organ function. Two types of amyloid commonly infiltrate the heart: immunoglobulin light-chain amyloid and transthyretin (TTR) amyloid. Among the TTR variants that predominantly target the heart, the valine to isoleucine substitution at position 122 (V122I or Ile122) is the most common. This TTR variant is responsible for the most frequent form of amyloid cardiomyopathy in the Caribbean basin. Increasingly study data supports a central role for circulating or pre-fibrillar amyloidogenic proteins in the disruption of cardiac function in TTR mediated amyloid disease. In vivo exposure of cultured cardiomyocytes to pre-fibrillar an amyloidogenic proteins stimulate the production of reactive oxygen species and disrupts calcium fluxes. (Recent studies indicate that pre-fibrillar amyloidogenic proteins may also induce apoptosis through the mitochondrial pathway, eventually leading to cardiac cell injury). Hence, growing evidence suggests that end-organ damage by pre-fibrillar TTR amyloid may be related to mitochondrial dysfunction. Diagnosis of cardiac amyloidosis can be based on invasive heart biopsies or a non-invasive approach including identification of amyloid tissue deposits from abdominal fat biopsies. The investigators aim is to demonstrate that transthyretin mediated amyloid disease alters the mitochondrial function of subcutaneous abdominal adipocytes.

The investigators objective is to study mitochondrial respiration assessed by oxygraphy in fragments of subcutaneous abdominal fat biopsies performed for diagnosis of TTR amyloidosis. Mitochondrial respiration will be evaluated in the absence and in the presence of ADP.

Follow the evaluation of mitochondrial respiration. So, no patient follow-up will be performed.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a parietal thickness measuring more than 15 mm on the echocardiography or have structural and echogenicity abnormalities characteristic of cardiac amyloidosis,
• Live in Martinique,
• Accept the use of the residues coming from biopsies of the subcutaneous abdominal adipose tissue performed during the medical care.

Exclusion criteria

• Be under 18 years old,
• Have a contraindication to subcutaneous biopsy,
• Be allergic to local anesthetics,
• Pregnant or nursing woman,
• Have a cardiovascular disease suggesting a secondary cardiac disease, such as documented severe hypertension, valvular stenosis, or a known familial cardiomyopathy,
• Be major under guardianship / curatorship or deprived of liberty,
• Not be able to answer to a simple administrative questionnaire or to give freely its non-opposition.