Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
NCT ID: NCT04925349
Last Updated: 2025-09-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
100 participants
OBSERVATIONAL
2021-08-30
2027-02-28
Brief Summary
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This trial will evaluate the role of innate immunity to influence disease progression in X-ALD, MLD and ALSP, and if the mutations related to these leukodystrophies result in a specific immune response leading to the pathogenesis.
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Detailed Description
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Several arguments support the contribution of the immune response and neuroinflammation in these three leukodystrophies. In X-ALD, activation of microglia (macrophages of the CNS) plays an essential role in the acute demyelination phase, where a severe inflammatory process occurs. In ALSP, the dysfunctional protein (CSF1R) is almost exclusively expressed in microglia. Even if MLD is not considered as a neuroinflammatory disease per se, microglia activation and increased inflammatory cytokines are observed in the brain of MLD patients and mice. Even if the most commonly accepted hypothesis is that neuroinflammation is caused by secondary activation of microglia following phagocytosis of myelin debris full of undegraded material, a primitive role of the inflammation due to macrophages (MAC) dysfunction has emerged in recent years.
MATRIX proposes to explore how disease-related mutations affect key components of MAC activation responses and how it reflects on their functionality.
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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affected subjects
* adult patients with adrenomyeloneuropathy/adrenoleukodystrophy
* children with adrenoleukodystrophy
* children with metachromatic leukodystrophy
Blood sample collection
blood sample collection
control subjects
* healthy children
* heatthy adults
Blood sample collection
blood sample collection
Interventions
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Blood sample collection
blood sample collection
Eligibility Criteria
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Inclusion Criteria
* Boys or girls aged between 15 months and 18 years (inclusive) diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
* Presymptomatic boys carrying ABCD1 mutations aged between 3 and 18 years (inclusive) (PRE-ALD)
* Adult males or females aged between 18 and 60 diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
* Males aged between 18 and 60 years diagnosed with AMN (elevated VLCFA and clinical symptoms of AMN without leukodystrophy at brain MRI)
* Males aged between 18 and 60 years diagnosed with CALD (elevated VLCFA with leukodystrophy at brain MRI)
* Adult males or females aged between 18 and 60 years diagnosed with ALSP (CSF1R mutation and leukodystrophy at brain MRI)
* Presymptomatic patient adults (males or females) carrying CSF1R mutations (PRE-ALSP)
* Children (15 months-18 years) without neurologic disease (no obvious neurological symptoms, normal neurologic examination)
* Adults aged between 18 and 60 years without neurologic disease (no overt neurological symptoms)
* Informed consent obtained :
* from the parents or guardian for children patients and children controls;
* from subject himself for adult patients and adult controls.
Exclusion Criteria
* Treatment likely to modify the immune system
* Unable to have a blood collection (i.e. low hemoglobin level at the investigator's judgment)
* Any other reason, to the discretion of the investigator
* Children or adults without health insurance or social security
15 Months
60 Years
ALL
Yes
Sponsors
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URC-CIC Paris Descartes Necker Cochin
OTHER
Assistance Publique - Hôpitaux de Paris
OTHER
Responsible Party
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Principal Investigators
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Fanny MOCHEL, MCU-PH
Role: PRINCIPAL_INVESTIGATOR
Institut du Cerveau et de la Moëlle épinière
Violetta ZUJOVIC, PhD, CR1
Role: STUDY_CHAIR
Institut du Cerveau et de la Moëlle épinière
Caroline SEVIN, PhD
Role: STUDY_DIRECTOR
Kremlin Bicêtre Hôpital
Locations
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AP-HP Hôpital Bicêtre
Le Kremlin-Bicêtre, , France
AP-HP Hôpital La Pitié Salpêtrière
Paris, , France
Countries
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Central Contacts
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Facility Contacts
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References
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Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, Ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013 Sep;16(9):1211-1218. doi: 10.1038/nn.3469. Epub 2013 Jul 21.
Weinhofer I, Zierfuss B, Hametner S, Wagner M, Popitsch N, Machacek C, Bartolini B, Zlabinger G, Ohradanova-Repic A, Stockinger H, Kohler W, Hoftberger R, Regelsberger G, Forss-Petter S, Lassmann H, Berger J. Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain. 2018 Aug 1;141(8):2329-2342. doi: 10.1093/brain/awy127.
Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie. 2014 Mar;98(100):135-42. doi: 10.1016/j.biochi.2013.11.023. Epub 2013 Dec 4.
Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. 2010 Feb;41(1):1-6. doi: 10.1055/s-0030-1253412. Epub 2010 Jun 22.
Other Identifiers
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IDRCB
Identifier Type: OTHER
Identifier Source: secondary_id
APHP190197
Identifier Type: -
Identifier Source: org_study_id
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