Gene/cell therapy for familial LCAT deficiency by auto-transplantation of lcat-gene transduced preadipocytes

JRCT ID: jRCTa030190230

Registered date:27/02/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Familial LCAT deficiency
• Date of first enrollment: 25/01/2017
• Target sample size: 3
• Countries of recruitment: Japan
• Study type: Interventional
• Intervention(s): Adipose tissue is extirpated from patient with familial LCAT deficiency syndrome and subjected to primary culture by ceiling culture. Normal LCAT gene is transduced into the obtained preadipocytes by retroviral vector-mediated gene transduction. Propagated LCAT-secreting preadipocytes are then subcutaneously transplanted into the patient.

Outcome(s)

• Primary Outcome: Purpose of this study is to evaluate adverse event(s) of LCAT replacement by auto-transplantation of lcat-gene transduced preadipocytes.
• Secondary Outcome: Effects of LCAT replacement on main symptoms of the LCAT deficiency (Plasma (or serum) LCAT activity, HDL-cholesterol, cholesteryl ester/total cholesterol ratio, renal manifestation, visual impairment, corneal opacity, and anemia) are exploratively evaluated.

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who are determined to be suffering from familial LCAT deficiency based on the following diagnosis criteria.
(1) Patient with LCAT genetic abnormality, as determined by a genetic diagnosis (test) (Excluding, however, patients in which LCAT Full length proteins are not expressed due to occurrence of termination codon or frame shift mutation).
(2) Patients present low HDL-cholesterol levels with one or some of following manifestation, Corneal opacity, Renal dysfunction (proteinuria), Hemolytic anemia.
(3) Plasma (or serum) LCAT activity is lower than the standard minimum limit.
2) Patients whose poor quality of life and prognosis are predicted due to clinical symptoms (especially corneal opacity and renal dysfunction) .
3) Patients older than 16.
4) Patient who provides written informed consent. If the patient is a minor, written consent must be obtained from the patient as well as a parent or guardian.

Exclude criteria

1) Patients that show no LCAT full length protein variation and/or patients in which LCAT proteins are not detected in the blood.
2) Patients with concomitant acute liver disease as a result of lipid metabolism (Acute hepatitis, cirrhosis of the liver) or kidney disease.
3) Mal- or undernourished, or suffering from a nutritional disorder such as Cachexia.
4) Will undergo a blood and/or plasma transfusion within one month prior receiving LCAT replacement therapy.
5) Patients testing positive for severe viral infection (Hepatitis B, Hepatitis C, HIV, Adult T-cell leukemia, Parvovirus B19, or Syphilis)
6) Liposuction surgery deemed too challenging to undergo.
7) Women who are pregnant, nursing, or could become pregnant
8) Patients suffering from an illness that leads to low blood cholesterol other than LCAT deficiency (ApoA-1 hypercholesterolemia, Tangier disease)
9) Patients determined ineligible by the principal-investigator and co-investigator in charge for any reason.

Related Information

• Primary Sponsor: Yokote Koutaro
• Source(s) of Monetary Support: CellGenTech, Inc.