Investigating Choroid Plexus Dysfunction in Neurological Diseases

Profound Cerebral Folate Deficiency as a Clinical Model for Identification of MRI and Biochemical Signatures of Choroid Plexus Dysfunction

This study is testing how problems with a part of the brain called the choroid plexus might be causing a rare neurological condition called LHIPFOLD in some patients and looking for possible treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 65 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 2 sites (Paris and 1 other locations)
• Trial ID: NCT06403189 on ClinicalTrials.gov

What this trial studies

This study focuses on cerebral folate deficiency (CFD) and its association with a newly identified neurological syndrome called LHIPFOLD, characterized by severe CFD and specific brain abnormalities. The researchers hypothesize that the dysfunction of the choroid plexus, which regulates the transport of metabolites like folate between blood and cerebrospinal fluid, may contribute to CFD in LHIPFOLD patients. The study aims to evaluate the choroid plexus function and identify other biochemical abnormalities that may be treatable. Participants will include patients with LHIPFOLD, neurological controls, and healthy volunteers, with interventions involving biological samples and MRI assessments.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with LHIPFOLD syndrome or those exhibiting symptoms consistent with this condition.

Not a fit: Patients with chronic diseases unrelated to neurological conditions or those without the specific manifestations of LHIPFOLD may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new insights and treatments for patients suffering from cerebral folate deficiency and related neurological conditions.

How similar studies have performed: While the approach of investigating choroid plexus dysfunction in relation to neurological diseases is relatively novel, similar studies have shown promise in understanding metabolic conditions linked to neurological symptoms.

Eligibility criteria

Inclusion Criteria:

For LHIPFOLD patients:

* Suspicion of diagnosis or diagnosis of LHIPFOLD syndrome documented in the medical record, i.e. presence of these three manifestations: severe intrathecal deficiency in 5MTHF\< 10 nmol/L, hyperproteinorachia \> 1 g/L, and white matter abnormalities on cerebral MRI.
* Patient covered by Social Security or Complementary Health Insurance or any equivalent scheme (including AME).

For Neurological Controls (NC) :

* No chronic pathology (notably no renal, cardiac, pulmonary or hepatic disease)
* Patients with one of the following neurological pathologies (confirmed diagnosis or strong suspicion), investigated in the course of routine clinical practice: Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, intracranial hypertension, normal pressure hydrocephalus, frontotemporal dementia.

For Healthy Volunteers (VS):

* No chronic pathology (in particular, no renal, cardiac, pulmonary, hepatic or psychiatric disease)
* No history of neurological pathology
* No chronic alcohol intoxication
* No consumption of toxic substances in the week preceding the inclusion visit
* No neurological or psychotropic medication.

Exclusion Criteria:

For all research participants:

* Age \<18
* Pregnant and breast-feeding women.
* Participant unable to give informed consent.
* Participant with a contraindication to MRI: implantable cardiac defibrillators, prostheses, transdermal patches, catheters; implantable pumps; artificial heart valves; implants to treat deafness (if incompatible with MRI); surgical neurostimulator clips., pregnancy, extreme claustrophobia.
* Participants with contraindications to contrast injection: known allergy to gadolinium chelates, severe renal insufficiency, pregnancy (BHCG for women of childbearing age prior to MRI), breast-feeding.
* Participants with contraindications to LP: haemostasis abnormalities (PT\<50%, platelets \< 40\*109/L), mass syndrome on brain imaging, suspected infection at or near the needle insertion site, coagulopathy, cardiopulmonary insufficiency or respiratory distress.

For NC and VS :

* Participant under legal protection (guardianship, curatorship)
* Participant not covered by Social Security or Complementary Health Insurance or any equivalent scheme (excluding AME).
* Taking folate, vitamin C or dietary supplements containing vitamins (excluding vitamin D and E) in the two months prior to inclusion.

Where this trial is running

Paris and 1 other locations

• CIC Neurosciences — Paris, France (Recruiting)
• Service de Neurologie, Pitié-Salpêtrière — Paris, France (Recruiting)

Study contacts

• Study coordinator: Yann NADJAR, MD

Conditions Plexus Choroideus; Metabolic Syndrome