신장 황반증 및 신장 관련 섬모병증의 틀에서 치료 목표에 대한 연구 (NPH1)
신장 황반증 및 신장 관련 섬모병증의 틀에서 치료 목표에 대한 연구 - NPH_1
Nephronophthisis (NPH) is an autosomal recessive, genetically heterogeneous disease, with mutations identified in over 20 genes (notably NPHP1 and NPHP4).
These genetic defects are associated with reduced urine concentration, chronic tubulointerstitial nephritis, etc., and progress to end-stage renal failure before the age of 20.
Nephronophthisis may occur as an isolated pathology, but is also often associated with various extrarenal symptoms.
NPHP genes account for around 50% of the genes responsible for NPH. No effective treatment is available to date.
Studying NPHP proteins and associated signaling pathways could help identify how to circumvent the problems of protein distribution and therapeutic mRNA, and could be applicable to a broad set of NPHP mutations. To this end, Dr. Saunier's laboratory at Institut Imagine has recently identified approved drugs that correct some of the ciliary and epithelial defects found in cells with NPHP mutations.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
Nephronophthisis (NPH) is an autosomal recessive, genetically heterogeneous disease, with mutations identified in over 20 genes (notably NPHP1 and NPHP4).
These genetic defects are associated with reduced urine concentration, chronic tubulointerstitial nephritis, etc., and progress to end-stage renal failure before the age of 20.
Nephronophthisis may occur as an isolated pathology, but is also often associated with various extrarenal symptoms such as retinal dystrophy, cerebellar vermis hypoplasia, skeletal dysmorphisms and/or situs/inversus. These disorders overlap phenotypically, genetically and functionally. All are thought to result from defective ciliary signaling and are classified as renal ciliopathies.
NPHP genes account for around 50% of the genes responsible for NPH. No effective treatment is available to date.
One possible therapeutic approach is to replace the defective protein; but delivery of recombinant proteins or mRNA to renal tubular cells is not currently feasible. However, each NPHP protein participates in numerous intracellular signalling pathways involving cilia functions.
Studying NPHP proteins and associated signaling pathways could help identify how to circumvent the problems of protein distribution and therapeutic mRNA, and could be applicable to a broad set of NPHP mutations. To this end, Dr. Saunier's laboratory at Institut Imagine has recently identified approved drugs that correct some of the ciliary and epithelial defects found in cells with NPHP mutations.
The global research project of which this protocol is a part seeks to identify new specific targets and develop new therapeutic agents against these targets for the treatment of NPH and other ciliopathies.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 해당 없음
연락처 및 위치
연구 장소
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La Defense, 프랑스
- 모병
- Imagine Institute
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연락하다:
- Sophie AF SAUNIER
- 이메일: sophie.saunier@inserm.fr
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- In order to be included in the protocol, subjects will have to respect the following criteria:
Affected patients:
Suffering from nephronophthisis or renal associated ciliopathies with known genetic diagnosis or not, Having obtained the signature of the informed consent form of patient, parent(s) or legal representative No age limit is requested for these patients, who can be recruited from birth.
Healthy relatives:
Being the healthy relative (father / mother / brother / sister) of an included patient Having signed the informed consent form (patient or parent in case of minor subject) No age limit is requested for these subjects, who can be recruited from birth.
'Negative' control patients: Being unscathed of any chronic renal disease, with or without ciliopathies Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth.
'Positive' control patients Suffering from Chronic Kidney Disease unrelated to ciliary dysfunction (such as glomerulopathy, tubulopathy…) Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth.
Exclusion Criteria:
In order to be included in the protocol, subjects will have to fulfill none of the following criteria:
Affected patients:
Patients with a functioning kidney transplant (only for patient for who urine sample is performed. This criteria is not applicable when only blood is sampling) Patients included in a therapeutic protocol since fewer 30 days.
Healthy relatives:
No no-inclusion criteria
'Negative' control subjects: No no-inclusion criteria
'Positive' control subjects: Patients with a functioning kidney transplant
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
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다른: Patients with nephronophthisis/renal associated ciliopathies
Affected patients: Suffering from nephronophthisis or renal associated ciliopathies with known genetic diagnosis or not, Having obtained the signature of the informed consent form of patient, parent Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells. |
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다른: Healthy relatives of Patients
Healthy relatives: Being the healthy relative (father / mother / brother / sister) of an included patient Having signed the informed consent form (patient or parent in case of minor subject) No age limit is requested for these subjects, who can be recruited from birth. Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells |
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다른: Negative control
Being unscathed of any chronic renal disease, with or without ciliopathies Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth. Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells |
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다른: Positive control
Suffering from Chronic Kidney Disease unrelated to ciliary dysfunction (such as glomerulopathy, tubulopathy…) Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth. Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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환자의 소변 유래 신장 상피 세포에서 잠재적 치료 표적의 양성 또는 음성 확인
기간: 3년
|
3년
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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NPHP 및 기타 신장 섬모병증 관리를 위한 소분자에 대한 반응을 평가하기 위한 바이오마커를 식별합니다.
기간: 3년
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3년
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Experimental transcriptomics data package from in vitro tubule cell model perturbed with disease network modifying agents
기간: 3 years
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The experimental design and data will be formatted for Bayesian analytics. |
3 years
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A rank ordered list of specific druggable nodes within the NPHP disease module that could be targeted by biologic or chemical entities.
기간: 3 years
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A rank ordered list of specific druggable nodes within the NPHP disease module that could be targeted by biologic or chemical entities. |
3 years
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- IMIS2015-05
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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