NEWS - YEAR 2021

FEBRUARY 2021

15 February 2021 
DUKE RESEARCHERS ACHIEVE FAVORABLE RESPONSE TO GENE THERAPY IN ALTERNATING HEMIPLEGIA OF CHILDHOOD (AHC) MOUSE MODEL

In this study the Duke research group of the Mikati Lab used an adeno-associated virus serotype 9 (AAV9) vector expressing the human ATP1A3 gene to add a normal copy of the ATP1A3 gene to the brain of AHC mice by injecting that vector into the cisterna magna (space within the skull just outside the base of the brain that has cerebrospinal fluid) and into the two lateral cerebral ventricles (spaces within the brain substance that are filled with cerebrospinal fluid).
The injections were performed in mice carrying the D801N mutation (Mahlool AHC mice). One group of these mice received the above active vector and another received a control vector without ATP1A3. Also control normal mice were injected.

Mice received the injections at age 10 days (P10) which corresponds to early infancy in human terms, the age at which AHC is usually diagnosed. The mice were then tested at age 40 days (P40, early adulthood) and 70 days (P70, mid adulthood).

     MikatiMices    

The findings were the following:

  1. Treatment increased ATP1A3 expression and function: There was strong expression of the injected gene in brain areas close to the injection sites (see Figure 1) with increase in the enzyme activity of the ATP1A3 ATPase.
  2. Treatment improved survival: It is already known that without treatment about half of the D801N mice die by around the age of 70 days. In this study, all the D801N mice treated with the active vector survived during the study period. On the other hand, as expected, half of the D801N mice who did not receive the active vector died.
  3. Treatment improved neurological function: At P40 there was reduction of inducible hemiplegia spells, and a significant improvement in balance of the mice who received the active vector.
  4. Improvement in neurological function was only partial: At age 70 days only a minimal effect on balance persisted and an effect on hemiplegia spells was not observed. Also, not all neurological function improved at either age (including inducible dystonia, strength and memory at either age 40 days or 70 days which did not differ between the treated group and the control mice).
MikatiMiceBrains     

Figure 1: Green Stain shows expression of ATP1A3. The illustration shows strong expression in an area close to the active vector injections site.
Note that the green stain is along the edges of the cells where the cell membrane is and where ATP1A3 is normally localized and where it normally functions.

 

This study demonstrates that, as a proof of concept, gene therapy can induce favorable effects in mice carrying the most common mutation causing AHC in humans. This encourages future research to improve the vector to allow more expression of ATP1A3 in all the brain (not just in areas close to the injection sites) for longer periods of time to get even more effects allowing translation to human trials.

by Prof. Mohamad Mikati (Duke University, Durham NC, USA)

read the report in pdf 


Reference: Hunanyan AS, Kantor B, Puranam RS, Elliott C, McCall A, Dhindsa J, Pagadala P, Wallace K, Poe J, Gunduz T, Asokan A, Koeberl DD, ElMallah MK, Mikati MA.Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool, Atp1a3Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood. Hum Gene Ther. 2021 Feb 12. doi: 10.1089/hum.2020.191. Epub ahead of print. PMID: 33577387. link

 

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NEWS - YEAR 2020

OCTOBER 2020

12 OCTOBER 2020 
AN ARTICLE ON AHC PUBLISHED IN RARE REVOLUTION MAGAZINE  

Read the article on AHC published in the Autumn 2020 edition of Rare Revolution Magazine entirely dedicated to rare and complex epilepsies.
Written by Rosaria Vavassori, our Data Manager, and Katherine Behl, vice-president of AHC-UK, the AHC patient association in Great Britain; both their children are affected by AHC.
https://bit.ly/3jQI4Wr

 Issue 017 AHC   AhcArticle1stPage    Autumn 017 2020 FINAL copy 

             

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NEWS - YEAR 2019

NOVEMBER 2019

30 November 2019 
DATA COLLECTION STARTED FOR THE IAHCRC INTERNATIONAL STUDY OBSERV-AHC

Data collection for the OBSERV-AHC Study (a Study of the IAHCRC Consortium) started last September 1st, in Spain, France, UK and USA, supported by their national patient associations. In Italy, they are still waiting for the approval of their Ethics Committee, but they too are ready to start as soon as they obtain it.
Data will be collected and entered in the IAHCRC-CLOUD Platform by the data-entry clinicians during the neurological visits to the patients organized in collaboration with their supporting patient associations.
The caregivers of the enrolled patients are offered the possibility to record their AHC episodes directly in the IAHCRC-CLOUD Platform, through its Mobile App, so that also their data can be included in the Study.

   Read Prof. Mikati's Article on the Neurology Website    ObservAhcDataCollectionItalyMar2019  
 

Prof. Mohamad Mikati presenting the OBSERV-AHC Study
at the International Symposium on AHC
organized by the Spanish Patient Association AESHA
and the Reference Center for AHC at the San Juan de Deu Hospital
in Barcelona, 9 February 2019

 

  Prsentation of the OBSERV-AHC Study
at the Family Meeting of the Italian Patient Association
in Milan, March 2019

 
 
  ObservAhcDataCollectionSpainSep2019   ObservAhcDataCollectionFranceSep2019  
  Family Meeting for the start of the data collection
for the OBSERV-AHC Study, organized by
the Spanish Patient Association in Barcelona, September 2019
 
  Family Meeting for the start of the data collection
for the OBSERV-AHC Study, organized by
the French Patient Association in Lyon, October 2019
 
 
  ObservAhcMeetingReykjavikOct2019    IahcrcCloudEventCalendarMobileBrowser02  
  Working meeting organized on the occasion of the
8th Symposium on ATP1A3 in Disease (Reykjavik, Iceland, 3 October 2019),
about the start of the data collection for the OBSERV-AHC Study.
Standing, Prof. Mohamad Mikati, Scientific Coordinator of the Study;
seated, the data-entry clinicians of the Centers participating in the Study,
in France, Spain, Italy, UK and the United States.
  The Mobile App through which a caretaker
can record the patient's events in the IAHCRC-CLOUD Platform

 

 
 

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NEWS - YEARS 2014 to 2018

SEPTEMBER 2018

17 September 2018 
PRESS CONFERENCE FOR THE PRESENTATION OF THE PROJECT IAHCRC-CLOUD PLATFORM
a service for the international research on AHC and the ATP1A3 diseases

Tuesday October 30 2018, 3.30pm
I.E.ME.S.T. Institute www.iemest.eu
via Michele Miraglia, 20 – Palermo, Italy

Palermo, 17 September 2018
The President of the Euro-Mediterranean Institute of Science and Technology (I.E.ME.S.T.) Bartolomeo Sammartino communicates that on Tuesday October 30 2018, at 3.30pm, the press conference will take place at the headquarters of the Institute (via Michele Miraglia, 20 – IT Palermo), for the presentation of the Project “IAHCRC-CLOUD Platform”, aimed at establishing an international platform for the data collection and sharing serving the collaborative studies of the IAHCRC Consortium.
The technical and ethical aspects will be presented, as well as the innovative features of the IAHCRC-CLOUD Platform, making it a Second Generation Rare Disease Registry, implementing the principles and methods of patient engagement and platform cooperativism.
The current studies of the IAHCRC Consortium using the Platform will also be presented; among them, the longitudinal Study OBSERV-AHC, coordinated by the Division of Pediatric Neurology - AHC and Related Disorders Program of the Duke University in Durham, NC USA. In addition, some anticipations will be given on future developments already foreseen for the Platform, to make it an open, scalable and adaptable tool for any other rare disease.
Please confirm your participation via email to This email address is being protected from spambots. You need JavaScript enabled to view it. by Friday October 26 2018.

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IAHCRC - International Consortium for the Research on Alternating Hemiplegia of Childhood and other ATP1A3 related diseases