The approach of LYSOGENE for treating lysosomal storage diseases is intracerebral in vivo gene therapy. A non-mutated gene coding for the enzyme deficient in the pathology is provided to brain cells by a single dose treatment.

The principal of therapeutic gene transfer

Gene therapy works by introducing genetic material into the cells to compensate for genetic abnormalities or to allow the secretion of the proteins required for the normal functioning of our metabolism. It is the delivery agent containing the gene that constitutes the treatment.

One common approach for medical gene transfer treatment consists in identifying a defective gene and then introducing a good version of this gene into the target cells via a therapeutic delivery agent. This gene will produce active protein which, by doing its job, will allow the patient's organism to function normally.

Delivering the therapeutic gene:

A delivery agent, known as a vector, is used to introduce the therapeutic gene to the patient's target cells. The most commonly used vectors are viruses which have been modified to carry normal human DNA.

LYSOGENE uses an adeno-associated virus (AAV) as the gene delivery vector which is a small virus containing non-pathogenic DNA that occurs naturally in humans. It has been used in numerous clinical trials.

It's use presents a number of advantages:

⁃ Safety: since according to our current understanding, the adeno-associated virus has never been associated with human disease.

⁃ Efficiency in the delivery of genes to the very heart of the cells. Genes delivered by the adeno-associated virus are known to produce functional proteins, at levels that can reach a therapeutic threshold, in an ongoing manner, from a single treatment.

⁃ Its ability to efficiently transduce numerous cellular types and in particular cells that do not divide, such as neurones.

⁃ Safety of treatment protocols and their low immunogenicity.

Depending on the target cell pathology, the vector is administered by injection into a specific part of the body, where it is absorbed by the individual cells (target cells).

An alternative consists in taking a sample of the patient's cells, exposing them to the vector in the lab, then cells containing the transgene are then reintroduced into the patient.

Treating lysosomal storage disease

There are various levels of therapy possible for the treatment of patients suffering from certain LSD's. The symptomatic treatments available for these diseases do not correct the primary cause of the disease and are mainly concerned with treating pain, behavioural and sleep problems, epilepsy, joint problems and deafness.

Supplementing the deficient protein is the only etiological treatment. It can be carried out by enzymotherapy, by Bone Marrow Transplant (BMT) or by gene therapy. Access to the central nervous system involves getting through or around the Blood-Brain Barrier (BBB), and today gene therapy is considered the only realistic option for  etiological treatments of the Central Nervous System (CNS).

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In vivo gene therapy
In gene therapy, the gene is considered as a drug which acts by replacing the function of the defective gene and by producing specific therapeutic proteins in the body in order to correct and/or fight against the disease. There are 2 main categories of gene therapy. The first, ex-vivo, consists in taking cells from the body, modifying them genetically and then replacing them into the patient. In the second category, in-vivo, the vector is introduced directly into the body tissue.

Our approach aims to make an intracerebral delivery, by a single dose treatment, of an AAV vector containing a non-mutated gene code for the enzyme deficient in that particular pathology. The vector will introduce the gene into the nucleus of the cells which will then be able to continue producing and secreting a functional enzyme.

Our treatment consists of an intra-cranial injection of a solution containing the therapeutic vector. The single neurosurgical procedure is based on a common stereotaxical practice that has undergone specific improvements approved by the appropriate authorities.