AHCF Raleigh Family Meeting July 2011 D Poncelin1 AHC research in Europe ITALY FRANCE ENRAH (European data base)

AHCF Raleigh Family Meeting AHCF Raleigh Family Meeting July 2011 D PoncelinJuly 2011 D Poncelin 11

AHC research in EuropeAHC research in Europe

ITALY ITALY FRANCE FRANCE ENRAH (European data base)ENRAH (European data base)

A.I.S.EA Onlus Italian Association for Alternating Hemiplegia

Via Sernovella, 37 – 23878 Verderio Superiore (LC) IT

WebSite http://www.aisea.org

AHCF Family Meeting Raleigh N.C., 22 – 24 July 2011

The Italian Association A.I.S.EA:

Activity report (2)

Development of the research

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Support to the ResearchThe 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)

www.ibahc.org

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Support to the ResearchThe 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 ProjectThe 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 websitewww.ibahc.org

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The I.B.AHC ProjectThe 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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“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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“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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• 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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• 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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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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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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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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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 ResearchOther 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)


AHC scientific research in AHC scientific research in FranceFrance

• Financial support by AFHA (French AHC Foundation), Financial support by AFHA (French AHC Foundation), through call for projects in France initially, now through call for projects in France initially, now extended to foreign projects (ex: Italian research.)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 (Application form available on request to AFHA (www.afha.org - mail to - mail to [email protected]) )

• collaborative projects are very much appreciated

• Maximum grant :40.000 € (57.000 $) per project


AHC scientific research in AHC scientific research in FRANCEFRANCE

Psychosocial issues in AHCPsychosocial issues in AHC: (Dr Auvin – Paris): : (Dr Auvin – Paris): Funded by AFHA : 19.000 €Funded by AFHA : 19.000 € questionnaire filled in by French families (31) about questionnaire filled in by French families (31) about

* parents’ main concerns and feelings (diagnostic * parents’ main concerns and feelings (diagnostic announcement, worries, information needs….) at time of announcement, worries, information needs….) at time of diagnosis and at time of the study. diagnosis and at time of the study.

* Social consequences for the family (parental couple, * Social consequences for the family (parental couple, professional life, siblings, social activities…) professional life, siblings, social activities…)

Results: answers analysed by neuropsychologist (J. Save) Results: answers analysed by neuropsychologist (J. Save) = poster presented during last european neuropediatric = poster presented during last european neuropediatric meeting in Crotia (May 2011) + scientific publication (in meeting in Crotia (May 2011) + scientific publication (in progress)progress)


Main results from the inquiryMain results from the inquiry Parental concernsParental concerns

With no change : pain, dystonia, cognitive outcomeWith no change : pain, dystonia, cognitive outcome at time of diagnosis: Hemiplegic spells, abnormal at time of diagnosis: Hemiplegic spells, abnormal

eyes movements, movement disorders,eyes movements, movement disorders, Later on: autonomy, behaviour , Later on: autonomy, behaviour ,

Parental most frequent needs:Parental most frequent needs: Information on disease outcome Information on disease outcome Role of early rehabilitation Role of early rehabilitation Treatment options Treatment options Management of AHC daily lifeManagement of AHC daily life Existence of a support group Existence of a support group


(Dr Nicole – Inserm Paris) (Dr Nicole – Inserm Paris)

Financial support from AFHA: 30.000 € (French DNA bank)Financial support from AFHA: 30.000 € (French DNA bank)

Study of the Glut 1 gene: negative results (pub 2011)Study of the Glut 1 gene: negative results (pub 2011)

Search for submicroscopic rearrangements linked to Search for submicroscopic rearrangements linked to alternating hemiplegia of childhood by SNP-CGH arraysalternating hemiplegia of childhood by SNP-CGH arrays

(poster presented Strasbourg 2010)(poster presented Strasbourg 2010)

FulFull Exome sequencing of DNA samples of AHC French l Exome sequencing of DNA samples of AHC French selected patients. Not yet started due to excessive cost selected patients. Not yet started due to excessive cost (5500 € each sequence) but will decrease significantly (5500 € each sequence) but will decrease significantly

within 2 years)within 2 years), which is a hope for all of us;, which is a hope for all of us;

AHC scientific research in AHC scientific research in FRANCEFRANCE


ENRAH (European Clinical DataBase)ENRAH (European Clinical DataBase)

Financial support from European CommunityFinancial support from European Community Clinical data collection from 157 European AHC patientsClinical data collection from 157 European AHC patients Scientific publication (Brain Oct 2010) = data analysisScientific publication (Brain Oct 2010) = data analysis Interesting points:Interesting points:

Determination of a paroxysmal disability index (based on Determination of a paroxysmal disability index (based on severity + duration + frequency of plegic and dystonic attacks)severity + duration + frequency of plegic and dystonic attacks)

Determination of a non-paroxysmal disability index (based on Determination of a non-paroxysmal disability index (based on global neurological impairement = walk , behaviour, global neurological impairement = walk , behaviour, communication,motor abnormalities, movement disorders, communication,motor abnormalities, movement disorders, mental retardation )mental retardation )


ENRAH (European Clinical DataBase)ENRAH (European Clinical DataBase)

Some interesting results ( tendencies, not individuals,datas coming Some interesting results ( tendencies, not individuals,datas coming mainly from MEDICAL FILES, to be confirmed by US data base ?)mainly from MEDICAL FILES, to be confirmed by US data base ?)

There is no evidence of relationship between paroxysmal There is no evidence of relationship between paroxysmal (« attacks ») index severity and non paroxysmal (« cognition ») (« attacks ») index severity and non paroxysmal (« cognition ») index severity = 2 children with almost same number of attacks index severity = 2 children with almost same number of attacks could have quite different cognitive impairement levelcould have quite different cognitive impairement level

Reported non paroxysmal index of severity (neurological Reported non paroxysmal index of severity (neurological disability) remain disability) remain constant with constant with age,= a child with a good index age,= a child with a good index will be usually an adult with good index (except for some will be usually an adult with good index (except for some individuals). This may suggest an initial (genetic ?) level of individuals). This may suggest an initial (genetic ?) level of severity of AHC, steady with age rather than a degenerative severity of AHC, steady with age rather than a degenerative course.(however may be subject to environmental status)course.(however may be subject to environmental status)

Death reports (7 in the study) : usually associated with severe Death reports (7 in the study) : usually associated with severe plegic attacks and epileptic seizures. No relationship with plegic attacks and epileptic seizures. No relationship with paroxysmal index (not more usual attacks), however non paroxysmal index (not more usual attacks), however non paroxysmal index (neurological impairement) is usually severe . paroxysmal index (neurological impairement) is usually severe .

What future for AHC research ?What future for AHC research ?

Here is my personal opinion having a look Here is my personal opinion having a look to the past years………to the past years………


4 requirements for AHC research to improve :4 requirements for AHC research to improve :

1.1. Money (Fundraising)Money (Fundraising)

2.2. Human material (DNA, tissues banks, clinical Human material (DNA, tissues banks, clinical data bases, participation of families to studies)data bases, participation of families to studies)

3.3. Advanced technology (i.e full exome sequence)Advanced technology (i.e full exome sequence)

4.4. Will and determination from scientists (quick + Will and determination from scientists (quick + positive results not guaranteed in AHC )positive results not guaranteed in AHC )

The future of AHC research will depend on the The future of AHC research will depend on the capacity for scientists and AHC organizations capacity for scientists and AHC organizations to combine to combine at the same time those 4 criterias at the same time those 4 criterias


Is collaborative research an answer ??Is collaborative research an answer ?? Genetic scientific approach (Full exome) seems to be the Genetic scientific approach (Full exome) seems to be the

same for French (Inserm) and American (SLC).same for French (Inserm) and American (SLC). several « clinical » research projects on AHC in progress several « clinical » research projects on AHC in progress

in various countries (mainly USA and Italy)in various countries (mainly USA and Italy) Financial support from Families foundations -up to now:Financial support from Families foundations -up to now:

USA (400.000 € ?) , Italy (200.000 €) , France (50.000 €) USA (400.000 € ?) , Italy (200.000 €) , France (50.000 €) The question is : What is the best ?The question is : What is the best ?

*international scientific collaboration to save time and *international scientific collaboration to save time and money by sharing material (DNA), work and results ? or money by sharing material (DNA), work and results ? or *keep on working independantly which leads to *keep on working independantly which leads to « competition » and may also speed up the research ?« competition » and may also speed up the research ?

The outcome of our AHC children will be linked to a clear The outcome of our AHC children will be linked to a clear answer to that questionanswer to that question


The end……The end……

As a conclusion for the future of AHC As a conclusion for the future of AHC international research , and because we international research , and because we are here in the USA, I should say :are here in the USA, I should say :

I HAVE A DREAM……..I HAVE A DREAM……..

YES WE CAN………YES WE CAN………



Thank you so much to all of you for listeningThank you so much to all of you for listening....

AHCF Raleigh Family Meeting July 2011 D Poncelin1 AHC research in Europe ITALY FRANCE ENRAH (European data base)

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