AHC research in Europe
 ITALY
 FRANCE
 ENRAH
(European data base)
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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AHCF Family Meeting
Raleigh N.C., 22 – 24 July 2011
The Italian Association A.I.S.EA:
Activity report (2)
Development of the research
A.I.S.EA Onlus
Italian Association for Alternating Hemiplegia
Via Sernovella, 37 – 23878 Verderio Superiore (LC) IT
WebSite http://www.aisea.org
Support to the Research
The I.B.AHC Project
 I.B.AHC – Biobank and Clinical Registry for
Alternating Hemiplegia is a project coordinated and
funded by A.I.S.EA Onlus, in collaboration with its Scientific
Committee and with the Biomolecular Laboratory of the
Scientific Institute “E. Medea”
 I.B.AHC is composed of two main repositories, the Clinical
Registry and the Biological Bank (Biobank), designed to
collect, organize, keep and share both the clinical data and
the biological samples (DNA, RNA and Cellular Lines) of
the patients affected by AHC.
 (40.000 € for the development of the on-line Registry
+ 60.000 € for the personnel costs + 30.000 € for
the data collection)
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Support to the Research
The I.B.AHC Project
The I.B.AHC Biobank and Clinical Registry are
Open to all research projects, with these
characteristics:



Only on AHC
Non lucrative
Good quality and not duplicated
Fully respectful of the privacy of the patients and of
their rights to the information about the projects using
their data and material and about the results, general
and individual, of these projects.
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The I.B.AHC Project
The Public Website www.ibahc.org
38 validated
cases currently
available,
complete with
their clinical data
and biological
samples.
The availability is
kept updated on
the I.B.AHC
public website
www.ibahc.org
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The I.B.AHC Project
The Public Website www.ibahc.org
From the
Documentation
Area of the public
website it is
possible to
download the
Informed Consent
Form for the
participation of the
patients, the
Access Request
Form for the
researchers and
other documents
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Research Projects funded and supported
by A.I.S.EA



“Alternating Hemiplegia of Childhood and Familial
Hemiplegic Migraine: distinct entities or part of
the same spectrum?” by G. Casari, F. Martinelli –
Boneschi, Milan (2004 – 2005, using the I.B.AHC
Biobank)
“Clinical Study of the Dysmorphic Features of
Alternating Hemiplegia”, by G. Neri, F. Gurrieri, Rome
(in progress, an article is in preparation for the
publication)
“Neurophysiological Dysfunctions in Alternating
Hemiplegia of Childhood – a Study with Evoked
Potentials” , by F. Vigevano, S. Rinalduzzi, Rome (2004
- 2005, published on the Scientific Journal Cephalalgia)
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Research Projects funded and supported
by A.I.S.EA




“A Clinical study of the Movement Disorders in AHC”, by E.
Fernandez Alvarez, Barcellona, N. Nardocci, Milan, A.I.S.EA
Scientific Committee (completed, using the I.B.AHC Clinical
Registry, results to be published)
“Study of the Cerebral Ematic Flux in AHC using the
Transcranial Doppler Sonography”, by E. Veneselli, M.
Stagnaro – Genova (completed, funded by A.I.S.EA 15.000 €,
publication in progress)
“Study of the excitability of the somatosensory system in
AHC”, by M. Valeriani – Rome (completed, funded by A.I.S.EA
15.000 €, publication in progress)
“Molecular Basis of Alternating Hemiplegia of Childhood”,
by M.T. Bassi – Bosisio Parini (LC) (completed, funded by
A.I.S.EA 20.000 €, using the I.B.AHC Biobank)
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Research Projects funded and supported
by A.I.S.EA



“International Classification of Functioning, Disability
and Health in subjects with alternating hemiplegia of
childhood”, by R. Borgatti, C. D’Aloisio, E. Ceppi(LC)
(funded by A.I.S.EA 15.000 €, published on "Disability and
Rehabilitation", 2009)
“AHC: a protocol for a Rehabilitation Follow-up and for
a Neuropsychologic Study”, by R. Borgatti (in progress)
“Sleep Study with Poligraphy”, by L- Nobili, C. Zucca (in
progress)
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Research Projects funded and supported
by A.I.S.EA
• Epigenetic Research (2008) by Doctors Kristel Van Geet
e Kathleen Freson, Center for Molecular and Vascular
Biology - Leuven, Belgium (using the I.B.AHC Biobank;
second phase not yet started)
• Genomic Analysis (2008) , by Prof. B. Dallapiccola, Dr. L.
Bernardini, Institute CSS Mendel, Rome (functional study
in progress, using the I.B.AHC Biobank and Clinical
Registry)
• Study of the GLUT1 Gene (2010), Prof. Veneselli, Dr.
Zara, Gaslini Institute – Genova (completed, using the
I.B.AHC Biobank and Clinical Registry, publication in
preparation)
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Research Projects funded and supported
by A.I.S.EA
• Exome Sequencing by Prof. G. Neri and Prof. F. Gurrieri,
University Cattolica, Rome (funded by A.I.S.EA – 15.000 €,
using the samples of 8 patients selected among the
patients in the I.B.AHC Biobank and Clinical Registry
according to their clinical and dysmorphic homogeneity, in
progress)
• Study of the Protocaderine Gene, by Prof. F. Vigevano,
Dr. E. Bertini and Dr. N. Specchio, Child Hospital Bambino
Gesù, Rome (approved for the use of the I.B.AHC Biobank
but not yet started)
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Research Projects funded and supported
by A.I.S.EA

Quality of Life “Alternating Hemiplegia: a study of the
paroxysmal episodes”, by E. De Grandis, M. Giannotta,
E. Veneselli, F. Franchini, R. Vavassori (2011 – 2012)

aim of the study is to collect at a large scale,
information about paroxysmal episodes (trigger factors,
frequency, management, treatment)

The collected data will be scientifically validated and
analyzed.

Expected results: to better document paroxysmal
episodes in AHC, to provide practical suggestions on
how to manage episodes and to ameliorate the quality
of life in AHC, as regards to treatment, psychological
support, supportive and educational therapy, patients’
needs.
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Research Projects funded and supported
by A.I.S.EA

Quality of Life “Alternating Hemiplegia: a study of the
paroxysmal episodes”, by E. De Grandis, M. Giannotta, E.
Veneselli, F. Franchini, R. Vavassori (2011 – 2012)

The data will be provided daily by the participating
patients

From the I.B.AHC public website www.ibahc.org, it is
possible to download all the information about the
Study and the Informed Consent Form for the
participation

The data can be provided either by entering them
directly in the on-line I.B.AHC Clinical Registry or by
filling a questionnaire (WORD and Excel formats)

The Study is funded and coordinated by A.I.S.EA Onlus
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Research Projects funded and supported
by A.I.S.EA

Quality of Life “Alternating Hemiplegia: a study of the
paroxysmal episodes”, by E. De Grandis, M. Giannotta, E.
Veneselli, F. Franchini, R. Vavassori (2011 – 2012)
One of the webforms to enter the data in the
on-line I.B.AHC Clinical Registry
The paper form to fill with the
data and send to A.I.S.EA
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Research Projects funded and supported
by A.I.S.EA

Quality of Life “Alternating Hemiplegia: a study of the
paroxysmal episodes”, by E. De Grandis, M. Giannotta, E.
Veneselli, F. Franchini, R. Vavassori (2011 – 2012)

The patients can apply until 31st December 2011

Currently 16 Italian patients and 6 European patients
have started to collect the data of their paroxysmal
episodes

The official languages of the Study are Italian, English
and French (available next September 2011)
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Support to the Research
Other activities
• Organization of the WORKSHOP ON ALTERNATING
HEMIPLEGIA, in collaboration with the Scientific Institute G.
Gaslini (Genoa, 11 November 2011)
• to involve the physicians in the participation of their
patients to the research projects
• To give an update about the current research projects
and research lines
• To define the best and shared procedures for the care of
the AHC patients
• Organization of the annual I.B.AHC Video-Session for the
Validation of the AHC Diagnosis (Genoa, 12 November
2011)
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AHC scientific research in France
•
Financial support by AFHA (French AHC Foundation),
through call for projects in France initially, now
extended to foreign projects (ex: Italian research.)
•
Various fields could be elected like:
•
AHC knowledge (genetic origins, neurological
dysfunction, epilepsy, diagnosis)
•
AHC health care (treatment, education needs,
social aspects, quality of life)
•
AHC outcome (medical follow up,social needs,
and evolution of AHC at adulthood)
•
Application form available on request to AFHA
(www.afha.org - mail to [email protected])
•
collaborative projects are very much appreciated
•
Maximum grant :40.000 € (57.000 $) per project
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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AHC scientific research in FRANCE
Psychosocial issues in AHC: (Dr Auvin – Paris):

Funded by AFHA : 19.000 €

questionnaire filled in by French families (31) about
* parents’ main concerns and feelings (diagnostic
announcement, worries, information needs….) at time of
diagnosis and at time of the study.
* Social consequences for the family (parental couple,
professional life, siblings, social activities…)

Results: answers analysed by neuropsychologist (J. Save)
= poster presented during last european neuropediatric
meeting in Crotia (May 2011) + scientific publication (in
progress)
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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Main results from the inquiry
Parental concerns
 With no change : pain, dystonia, cognitive outcome
 at time of diagnosis: Hemiplegic spells, abnormal
eyes movements, movement disorders,
 Later on: autonomy, behaviour ,
Parental most frequent needs:
 Information on disease outcome
 Role of early rehabilitation
 Treatment options
 Management of AHC daily life
 Existence of a support group
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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AHC scientific research in FRANCE
(Dr Nicole – Inserm Paris)
Financial support from AFHA: 30.000 € (French DNA bank)
Study of the Glut 1 gene: negative results (pub 2011)
Search for submicroscopic rearrangements linked to
alternating hemiplegia of childhood by SNP-CGH arrays
(poster presented Strasbourg 2010)
Full Exome sequencing of DNA samples of AHC French
selected patients. Not yet started due to excessive cost
(5500 € each sequence) but will decrease significantly
within 2 years), which is a hope for all of us;
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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ENRAH (European Clinical DataBase)
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Financial support from European Community
Clinical data collection from 157 European AHC patients
Scientific publication (Brain Oct 2010) = data analysis
Interesting points:


Determination of a paroxysmal disability index (based on
severity + duration + frequency of plegic and dystonic attacks)
Determination of a non-paroxysmal disability index (based on
global neurological impairement = walk , behaviour,
communication,motor abnormalities, movement disorders,
mental retardation )
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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ENRAH (European Clinical DataBase)

Some interesting results ( tendencies, not individuals,datas coming
mainly from MEDICAL FILES, to be confirmed by US data base ?)

There is no evidence of relationship between paroxysmal
(« attacks ») index severity and non paroxysmal (« cognition »)
index severity = 2 children with almost same number of attacks
could have quite different cognitive impairement level

Reported non paroxysmal index of severity (neurological
disability) remain constant with age,= a child with a good index
will be usually an adult with good index (except for some
individuals). This may suggest an initial (genetic ?) level of
severity of AHC, steady with age rather than a degenerative
course.(however may be subject to environmental status)

Death reports (7 in the study) : usually associated with severe
plegic attacks and epileptic seizures. No relationship with
paroxysmal index (not more usual attacks), however non
paroxysmal index (neurological impairement) is usually severe .
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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What future for AHC research ?
 Here
is my personal opinion having a look
to the past years………
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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4 requirements for AHC research to improve :
1.
2.
3.
4.

Money (Fundraising)
Human material (DNA, tissues banks, clinical
data bases, participation of families to studies)
Advanced technology (i.e full exome sequence)
Will and determination from scientists (quick +
positive results not guaranteed in AHC )
The future of AHC research will depend on the
capacity for scientists and AHC organizations
to combine at the same time those 4 criterias
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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Is collaborative research an answer ??
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Genetic scientific approach (Full exome) seems to be the
same for French (Inserm) and American (SLC).
several « clinical » research projects on AHC in progress
in various countries (mainly USA and Italy)
Financial support from Families foundations -up to now:
USA (400.000 € ?) , Italy (200.000 €) , France (50.000 €)
The question is : What is the best ?
*international scientific collaboration to save time and
money by sharing material (DNA), work and results ? or
*keep on working independantly which leads to
« competition » and may also speed up the research ?
The outcome of our AHC children will be linked to a clear
answer to that question
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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The end……
 As
a conclusion for the future of AHC
international research , and because we
are here in the USA, I should say :
I HAVE A DREAM……..
YES WE CAN………
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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Thank you so much to all of you for listening..
AHCF Raleigh Family Meeting
July 2011 D Poncelin
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L’AFHA communique - AHC Association of Iceland