Novel Gene Therapies for Rare Diseases in Development

Release Date: 29-Nov-2020

The investigators are rapidly developing next generation of gene therapies to treat rare disease. The above can be justified by the investment done by Generation Bio in January,2020 of about US $110 million which was raised to US $230 million in thr next six months. Despite COVID19,the company has they have done enormous work for the gene therapies in the clinical trials. With the FDA approval of two drugs - Spark Therapeutics’s Luxturna for RPE65 mutation-associated retinal dystrophy and Novartis’ Zolgensma for spinal muscular atrophy (SMA), the market has seen tremendous growth in developing different approaches for gene therapy.


Currently, Generation has designed novel gene therapies for the treatment of Hemophilia A and phenylketonuria which are in preclinical stages. The gene therapy has a new approach of delivery as they don't use virus, instead they use alternative technology that avoids touching off an immune responseandmdash;a buildup of antibodies to the virus that would normally prevent a second round of treatment. The core technology of Generation called as non-viral closed ended DNA is carried into the body by lipid nanoparticle. The therapy has potential to sidestep immune response which can be used in diseases like phenylketonuria where the gene correction needs to reach liver cells.


Valoctocogene roxaparvovec, which is an adeno-associated virus (AAV)-based gene therapy is developed by BioMarin which has the potential to change the future technology. To understand the cellular determinants of expression, scientists are currently studying liver biopsy tissues. Further BioMarin is working in collaboration with Swiss startup Dinaqor to develop gene therapies to treat heart diseases such as hypertrophic cardiomyopathy. For this, the utilize capsids which can travel to heart instead of liver.


Taysha gene therapy was launched in 2019 which aim to correct the genetic nervous system disorders by delivering the gene therapy to the spinal fluid. Currently, the novel gene therapy is being evaluated for its role in three neurodegenerative disease. The gene therapy for GM2 gangliosidosis, a disease that progressively destroys nerve cells, is different for more than its intrathecal delivery. The therapy uses a single viral vector to deliver two genes at the heart of the disorderandmdash;HEXA and HEXB. They’re linked by a self-cleaving peptide and a promoter, “which allows the two genes to be expressed at a one-to-one ratio, mimicking the endogenous system of a healthy cell.


Further, Passage Bio is using a next-generation viral vector called AAVhu68 for GM1 gangliosidosis. The preclinical studies have found that there is increase expression of the protein in targeted cells as well as cerebrospinal fluid. In August, the trial was put on hold by FDA regarding the concern of the delivery system.


A gene therapy for the hunter syndrome and fabry disease is also developed by Avrobio which mainly focuses on the cross correction in gene therapy. Its technology platform, called plato, consists of a lentiviral vector and “tags” that help the therapeutic proteins reach the target cells’ lysosomesandmdash;the organelles inside of cells that orchestrate vital processes in the body. The company has announced that the response last for 3.5 years in phase-1 and 2 of the Fabry disease.


Another company LogicBio Therapeutics’ focuses on moving gene therapy into the future is to harness the power of genome editing. For this, they have developed  GeneRide technology which uses strands of DNA to deliver a functioning copy of a faulty gene into nuclei, prompting natural DNA repair mechanisms to insert the good gene exactly where it belongs in the chromosome. The therapeutic gene becomes part of that cellandmdash;and of its daughter cells when it dividesandmdash;potentially preventing a dilution of effect over time that can occur with other gene therapies.

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