Today, the urgency of the situation to save these children leads us to approach research in three priority areas:
1- Gene therapy, sticto sensu:
Gene therapy involves introducing genetic material into cells to treat a disease. Initially, this approach was designed to replace a defective gene in the case of a monogenic disease (i.e. linked to the dysfunction of a single gene). However, over the last two decades, the rapid development of knowledge and technology has made it possible to increase the number of possible strategies and to extend their use to a wide range of indications.
The development of a gene therapy programme itself is time consuming and costly ( several million euros ) but must be considered now in order to be able to offer a sustainable therapeutic response to future children affected by the KCNT1 gene mutation.
2 – Antisense therapy ( ASO ):
It is a form of treatment for genetic diseases and infections. When a particular gene is known to be responsible for a particular disease, it is possible to synthesise a complementary strand of nucleic acid (DNA, RNA, or a chemical analogue) to bind to the messenger RNA (mRNA) of the gene during its expression. This results in the gene being inactivated or the corresponding protein being changed.
Across the Atlantic, several teams are working on the development of antisense oligonucleotide drugs tAo suppress the de novo mutation in the KCNT1 gene.
This form of therapy gives affected individuals the chance to develop like other children, and neurogenetics in the United States is ready to act, but it comes at a significant cost of 1.7 M € per patient, with several children eligible.
A transfer of technology between the USA and Europe, and more particularly with France, is on the horizon, but requires the creation of a register of patients affected by the KCNT1 gene mutation.
The rapid implementation of this updated register across France and Europe is a priority and represents a cost of around 100,000 euros.
3 – Repositioning of molecules:
It is the search for molecules already approved in humans (already benefiting from the MA) in order to stem the effects of the genetic mutation. This is the case, for example, with Quinidine ( molecule initially used in patients with heart disease ) which has a beneficial effect in some KCNT1 children.
French biotechs are specialised in drug discovery and repositioning in the field of rare monogenic diseases, and their technology allows them to carry out individualised research projects and identify, within a few months, new drug candidates in collaboration with patient associations, doctors and academic and industrial partners.
These projects represent a cost of approximately 150,000 to 200,000 € per year.