AHC research in Europe

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AHC research in Europe

• ITALY
• FRANCE
• ENRAH (European data base)

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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
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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 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. DAloisio, 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 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)

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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 d.poncelin_at_libertysurf.fr)
  
• collaborative projects are very much appreciated
• Maximum grant 40.000 (57.000 ) per project

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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)

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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

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(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
AHC scientific research in FRANCE
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ENRAH (European Clinical DataBase)

• 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 )

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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 .

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What future for AHC research ?

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

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4 requirements for AHC research to improve

• 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

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Is collaborative research an answer ??

• 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

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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

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