Neuroimaging in PLA2G6-Associated Neurodegeneration(NEU-PLAN) Version1

• Research type

  Research Study

• Full title

  Neuroimaging in PLA2G6-Associated Neurodegeneration

• IRAS ID

  274415

• Contact name

  Manju Kurian

• Contact email

  manju.kurian@ucl.ac.uk

• Sponsor organisation

  UCL Great Ormond Street Institute of Child Health

• Duration of Study in the UK

  2 years, 3 months, 12 days

• Research summary

  PLA2G6-Associated Neurodegeneration(PLAN) is a devastating form of Neurodegeneration with Brain Iron Accumulation(NBIA) due to mutations in the PLA2G6 gene. The commonest form of PLAN is called Infantile Neuroaxonal Dystrophy(INAD). INAD is an ultra-rare, progressive condition that affects infants and young children. Over time, affected patients lose the ability to walk, talk and feed independently. This is a life-limiting condition with premature mortality in childhood or early adolescence.

  There are currently no treatments that cure this disease or slow down its progression. Fortunately, new therapies are now on the horizon for INAD including gene therapy that is showing promising results in animal models. There is now an urgent need to develop robust outcome measures for the evaluation of newly developed treatments for INAD patients.

  In published literature and clinical practice, experts have observed a shrunken appearance of the back of the brain (cerebellar atrophy) on brain Magnetic Resonance Imaging (MRI) scans in patients with INAD. There is also appearance of excess iron deposition that accumulates in a different more central part of the brain (basal ganglia) at later stages of the disease.

  This study aims to conduct a more detailed and comprehensive brain MRI study in INAD patients by:
  (i) Quantifying the volume loss in the brain, specifically within the cerebellum
  (ii) Quantifying the brain iron accumulation, specifically within the basal ganglia area
  (iii) Analyse the brain network connectivity and microstructure
  (iv) Studying repeat neuroimaging over a 12 to 24 month period to better understand how these changes evolve over time

  The overarching goal is to develop neuroimaging as an objective measure of INAD disease progression and improve understanding of the disease process. In the absence of existing biomarkers for this disease, this proposed analysis would greatly facilitate the evaluation of novel treatments and accelerate the development of disease-modifying therapies.

• REC name

  London - City & East Research Ethics Committee

• REC reference

  20/LO/0715

• Date of REC Opinion

  21 May 2020

• REC opinion

  Favourable Opinion