The main, primary objective of this study is identification of the molecular mechanisms that regulate structure and function of red blood cells in patients with neurodegeneration accompanied by the presence of abnormal red blood cells (…
ID
Source
Brief title
Condition
- Red blood cell disorders
- Structural brain disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are characteristics of red blood cell structure and
function in vitro:
A. deformability in capillary flow conditions.
B. deformability in spleen-like conditions.
C. cell morphology.
D. cell membrane composition.
E. metabolic status.
F. characteristics and kinetics of erythropoiesis in vitro.
G. active signaling pathways.
Secondary outcome
na
Background summary
In recent years, there has been an increasing awareness in the biomedical
community that function and survival of the red blood cell are finely tuned and
regulated processes [1]. This insight has been parallelled by the development
and application of new tools for the study of red blood cell physiology.
Intricately interwoven with these studies, it has become clear that red blood
cells are involved in various systemic diseases, such as diabetes, iron
accumulation, and inflammation [2-4]. Also, the ready availability of red
blood cells is an important advantage compared with that of cells from all
organs, in particular the brain.
The composition of the red blood cell membrane is one of the best known in
modern cell biology, but the molecular mechanisms of the (regulation of the)
interaction between lipid bilayer and cytoskeleton are far from understood. The
effects of disturbance of this interaction on cell morphology, deformability
and survival have, so far, mostly been deduced from red blood cell-centered
genetic diseases such as sickle cell disease and other *membranopathies* [5].
Relatively little is known on the regulation of physiological aging and
removal, and even less on the effects of disturbance of these processes on the
homeostasis of the whole organism. Recent data from proteomic and metabolomic
studies strongly suggest that red blood cells have a functional interaction
with soluble and cellular components of the circulation, such as cytokines,
lipids, endothelial cells, and immune cells [6, 7]. Such data also indicate
that elucidation of the mechanisms underlying abnormal red blood cell shape may
be instrumental in understanding the pathopysiology of other cells, including
degenerating neurons in the basal ganglia [8].
Thus, there is an urgent need to identify the molecular mechanisms that
regulate function and survival of the red blood cell in health and disease.
More specifically, molecular identification of the mechanism leading to the
formation of acanthocytes has, so far, been the only way to study the
pathobiology of neuroacanthocytosis (chorea-acanthocytosis, McLeod disease,
Huntington disease-like II, neurodegeneration with brain iron accumulation)
affecting the basal ganglia [9].
Study objective
The main, primary objective of this study is identification of the molecular
mechanisms that regulate structure and function of red blood cells in patients
with neurodegeneration accompanied by the presence of abnormal red blood cells
(neuroacanthocytosis). Hereto, selected characteristics of the red blood cells
of patients will be compared to those of healthy donors, before or after
experimental manipulation in vitro (see als the section 'primary study
parameters').
Secondary objectives are: (1) an understanding of the mechanism of
neurodegeneration in patients with neuroacanthocytosis; (2) the development of
biomarkers for diagnosis and disease progression.
The first step towards these objectives is an inventory of the molecular
characteristics of the red blood cells of patients with neuroacanthocytosis, in
comparison with those of healthy donors.
Study design
Our study will be an explorative, observational study, consisting of a
comparison of structure and function of red blood cells of patients with
neuroacanthocytosis with those of healthy, age-matched and gender-matched
control donors in vitro.
The duration of the study is five years; the setting of the study is within one
of the research lines of the Department of Biochemistry, Radboud University
Medical Centre: *The Red Blood Cell in Health and Disease* and the E-RARE/ZONMW
project *Advancing the European Multidisciplinary Initiative on
Neuroacanthocytosis EMINA-2: dissecting the molecular pathophysiology of
chorea-acanthocytosis // Signalling cascades involved in neuronal and
erythrocyte dysfunction in ChAc*.
Study burden and risks
The only burden and risks associated with this study are those that are
associated with a venipuncture of 5-15 ml blood by qualified personnel,
identical to the procedure that is used for routine diagnostic purposes.
Geert Grooteplein 28
Nijmegen 6525 GA
NL
Geert Grooteplein 28
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
control donors: healthy, 18-55 years old
patients: clinical diagnosis neuroacanthocytosis
Exclusion criteria
controls: use of medication with a known effect on red blood cells structure and/or function
patients: inability to obtain sufficient data for a clinical diagnosis
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL45934.091.13 |