Therapeutics Tracks - Other Tracks :

New leads are opening up which could have applications for numerous rare diseases. In particular, they allow direct intervention on the gene or the “message” transmitted by the gene to the cell. In this way :

- mixed oligonucleotides (an RNA and a DNA hybridised together) have the capacity to link to a specific part of the genome (where there is a mutation) and to cut off the DNA in order to remove and replace the zone with the mutation responsible for the disease. This technique is under study in animals for haemophilia B, Crigler-Naajar syndrome and oculocutaneous albinism.

- exon skipping allows the elimination of the mutated part of the RNAm and makes possible the production of a slightly different but functional protein. At Généthon, highly important first results concerning Duchenne muscular dystrophy have been obtained in the mouse. In less than two years, Généthon succeeded in repairing the muscles of mouse models of Duchenne myopathy by re-establishing production of a truncated but functional protein. This technique has also been applied pre-clinically to betathalassemia. Also concerned are other diseases whose truncated proteins retain their function: for example haemophilia A or epidermylosis bullosa. In partnership with the company Genatlas the AFM has just launched a programme for the identification of candidate rare genetic diseases to which this technique could apply. For its part, Généthon is preparing a human clinical trial for 2007.

- antisense oligonucleotides can modulate the expression of a gene. In pre-clinical studies, this technique is applied to genetic dominant diseases with triplet expansion such as Steinert’s myotonia, fragile X syndrome, spinocerebellar ataxia, Friedreich’s ataxia or Huntington’s disease.

- transreading of a stop codon allows a premature stop in protein production to be released, with the aid of products. This concerns certain patients affected with Duchenne muscular dystrophy, cystic fibrosis or type 1 mucopolysaccharidosis.

- stimulating the expression of a foetal or alternative gene thanks to certain pharmaceutical products can lead to compensation for the defective protein. This technique could be particularly applied to spinal amyotrophies (SMN2 gene), Duchenne muscular dystrophy (utrophin gene), betathalassemia drepanocytosis (foetal haemoglobin gene).

- recombinant proteins can be developed to compensate for their deficiency, as in Fabry’s disease and Gaucher’s disease.