September 21, 2017

expert reaction to study looking at gene immunotherapy in mice with multiple sclerosis

In a new study published in Molecular Therapy researchers – using gene immunotherapy – were able to demonstrate the prevention and reversing of the symptoms of multiple sclerosis (MS) in mice.

Dr Gillies O’Bryan-Tear, spokesperson for the Faulty of Pharmaceutical Medicine and independent Pharmaceutical Physician, said:

“This is a thorough and well-controlled set of experiments in which the authors have demonstrated that the delivery of a mouse gene encoding a mouse myelin sheath protein, myelin oligodendrocyte glycoprotein (MOG), into mice with an experimentally induced form of multiple sclerosis (MS), can prevent and reverse disease symptoms, even in mice with relatively late stage disease.  The carrier mechanism, using attenuated adenovirus AAV8 to transport the gene, is well-established in the field of gene therapy, and in use currently in a wide variety of human trials in different genetic diseases.  This approach is different from most others, in that the authors were attempting to induce immune tolerance to a ‘self’ antigen, MOG, by stimulating a subclass of T cells, so-called T regulatory cells, which are known to be important in sustaining immune tolerance to ‘self’ antigens.  In MS, this immune tolerance goes awry and one of the proteins thought to be important, and to which the MS patients mount an immune response, is MOG.  There are other myelin sheath proteins implicated in MS also, so that induction of tolerance to one protein may not predict clinical success: nevertheless the resolution of symptoms shown in these mice was impressive, implying that MOG is a driver of the disease at least in the mice.

“The experiments were well conducted, very well controlled, and repeated: the conclusions are not over-stated.

“This opens up a promising new avenue of human research, not only for MS, but also potentially for other auto-immune diseases such as Type 1 diabetes, if a suitable causative self antigen can be identified and successfully placed in an viral carrier such as AAV8.  Clearly, it will take several years to construct and test the human version of the mouse gene which was used in these mouse experiments; nevertheless, this study adds to the growing excitement being generated in the field of gene therapy, with two products already marketed and several more on the way.”

* ‘Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis’ by Geoffrey D. Keeler et al. published in Molecular Therapy on Thursday 21 September 2017. 

Declared interests

Dr Gillies O’Bryan-Tear: “I currently advise Audentes, a US company developing gene therapies for rare genetic disorders. I hold no stock in the company.”