The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration (PROTEINOSKIN)

Nantes University Hospital (NUH)

Status: Enrolling

Conditions: Frontotemporal Lobar Degeneration

Treatments: Procedure: Skin biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT06490822

RC23_0575

Details and patient eligibility

About

Frontotemporal lobar degeneration (FTLD) is a clinically heterogeneous syndrome, characterized by progressive decline in behaviour and/or language. From a pathological standpoint, like the great majority of neurodegenerative disorders, FTLD are proteinopathies, which are characterized by the presence of specific protein deposits in the Central Nervous System (CNS). Accordingly, the two main deposits observed in FTLD are either made of Tau or transactive response DNA binding protein 43 (TDP-43).

In pathological conditions such as FTLD, both proteins are aggregated and hyperphosphorylated.

It is now well established that the pathological process in some proteinopathies such as synucleinopathies (of which Parkinson's disease is the main representative) is not limited to the brain but also widespread throughout the peripheral autonomic networks, including the autonomic innervation of the skin. In this context, many independent studies have shown that the pathological process in PD could be detected using routine punch skin biopsies opening the way for the development of original histopathological markers of the disease.

Our hypothesis is that such a scenario could also occur in FTLDs and that the detection of the pathological tau or TDP-43 protein in the skin could help in diagnosing FTLD. This is especially relevant as, despite the recent progress in genetics, neurobiology and neuroimaging, there are no available biomarkers for FTLD.

Full description

Participant with Frontotemporal Lobar degeneration equally distributed into behavioral variant of frontotemporal dementia (bvFTD), language variant with primary progressive aphasia (PPA) and motor presentations with atypical parkinsonian disorders (corticobasal degeneration-CBD and progressive supranuclear palsy-PSP) and motoneuron disorder (amyotrophic lateral sclerosis -ALS) will be included at Nantes University Hospital during a period of 24 months.

Healthy volunteers will be included as comparative group. A skin biopsy and venous blood samples will be collected for all participants.

Enrollment: 80 estimated patients

Sex: All

Ages: 50 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (patients):

• Adressed or followed at memory clinic or ALS expert center at Nantes university hospital.
• Aged 50-75 years
• Fulfilling current diagnosis criteria for one of the disorder: vcfFTD, non-Alzheimer PPA (semantic or non fluent), DCB or PSP,ALS
• MMSE ≥ 18
• Membership of social security scheme

Inclusion Criteria (healthy volunteers):

• No history of neurological disease, diabetes, or alteration/damage of peripheral nervous system
• Aged 50-75 years Paired to at least one patient on age (less or more 5 years)
• MOCA ≥ 26
• Membership of social security scheme

Non inclusion Criteria (Patients and healthy volunteers):

• Concomitting conditions affecting the peripheral nervous system such as but not limited to diabetes, renal failure, thyroid disorder, vitamin B12 deficiency, acute and chronic inflammatory diseases HIV, syphilis
• Know allergy to local anesthetic
• Known coagulopathy
• Pregnant women or breastfeeding women
• Person under court protection sous sauvegarde de justice
• Person under guardianship
• Inability to sign an informed consent

Non inclusion criteria (Patients) • Patient with neurological disease other than FTLD

Non inclusion criteria (Healthy volunteers) :

• Evidence of neurological disorder at the inclusion including but not limted to FTLD, Parkinson disease, Alzheimer disease, lewy body dementia, Huntington disease, systemic lupus erythematosus multiple sclerosis; learning disabilities, mental retardation, severe hypoxic brain injuries, brain trauma with permanent cognitive impairments.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

Single arm study

Other group

Description:

A single 3 mm-diameter punch skin biopsy will be obtained from FTLD patients and healthy volunteers at the C8 paravertebral under local anesthesia to analyze cutaneous innervation

Treatment:

Procedure: Skin biopsy