NEWS - YEAR 2021


15 February 2021 

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).


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).

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



19 January 2021 

We are pleased to share a fantastic news, coming from five IAHCRC member Centers, in Spain (Dr. Carmen Fons, Hospital Sant Joan de Déu - Barcelona), in Italy (Dr. Francesco Danilo Tiziano, Università Cattolica del Sacro Cuore - Rome and Dr. Elisa De Grandis, Istituto G. Gaslini - Genoa), in France (Dr. Eleni Panagiotakaki, University Hospitals of Lyon) and in the USA (Prof. Mohamad Mikati, Duke University - Durham NC).
The TREAT-AHC Study that the four European Centers presented at the 2019 edition of La Marató de TV3 has been approved for funding! Objective of the Study, led by Dr. Tiziano, is to identify compounds for the treatment of AHC through drug repositioning and the design and validation of a specific clinical scale.
Warmest congratulations to the TREAT-AHC team, and best wishes for a profitable and rapid completion of their Study.
La Marató de TV3 is the annual telethon broadcast by Televisió de Catalunya and the homonymous Foundation, to raise funds for scientific research on diseases that are currently incurable. For more information on all the projects approved for funding (in Spanish) visit this link
    Treat-AHC Study receives funding       


18 January 2021 

Today is the International Day of Alternating Hemiplegia of Childhood (AHC)!
On January 18, 2012 the ATP1A3 gene was discovered to be the primary cause of AHC, thanks to an international research project supported by the patient associations in the USA and in Europe.
Since then, this day has been celebrated to raise awareness about this ultra-rare neurodevelopmental disease that affects only one in a million people.
For today and the rest of this week, we will join the families all over the world in sharing information about AHC as well as photos from the #oneinamillion campaign.


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