We all injure ourselves often- a cut finger when doing the washing up, that scab we can’t resist picking. We don’t usually think much of it, maybe a quick curse, but the wound stops bleeding, stops hurting and heals. But what would happen if scabs didn’t form and if small cuts didn’t stop bleeding? Well for some people this is the case. Haemophilia A, a haemorrhagic disorder, is generally an X-linked recessive trait and effects 1 in 10000 males. It involves defects of plasma protein coagulation Factor VIII (FVIII) responsible for blood coagulation. Different mutations of FVIII result in varying degrees of severity with symptoms varying from excessive bleeding only after a severe trauma or surgery to frequent internal and external bleeds. Currently therapy entails protein replacement in the form of infusions of FVIII, however due to regular infusions antibodies to FVIII may develop.
Luckily there is a canine model for haemophilia A. In a recent paper ‘Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A’ they use this canine model to show that gene therapy provides a continuous locally inducible treatment for maintaining the regulation of blood in haemophilia A.
What Is Gene therapy?
Every organism is encoded for by DNA, this DNA is built up of genes which encode proteins which in turn make up everything of that organism. Therefore genes control every aspect of your body, from eye colour to how each cell works. Mutations in genes can therefore affect proteins and result in disease such as haemophilia A. Gene therapy involves the use of healthy genes to treat an illness. This healthy gene will encode a healthy protein of which the body is lacking. This gene is generally taken into the cell via a vector such a virus which can enter the cell and deliver the genetic material.
How can it be used to treat Haemophilia A?
The previously mentioned study used a type of virus known as lentiviruses as the vector to deliver the FVIII gene into hematopoietic stem cells of the canine model organism. The platelets derived from these hematopoietic stem cells therefore have the healthy gene and can produce FVIII- this resulted in a moderate increase of FVIII sufficient to provide therapeutic benefit to these dogs for at least 2.5 years.
Impact on Medicine
Due to the inhibitory antibody response to current protein replacement therapy of FVII , meaning the effectiveness of treatment decreases over time, finding novel treatments of haemophilia A is necessary. Gene therapy may be the future for treatment as supported by this paper. Gene therapy offers longetivity of treatment which would replace the current frequent injections of FVIII. Due to the wide range of roles of platelets it is also a possibility that this study may be the basis for the treatment of a wide spectrum of inherited disorders.
The best may be yet to come
Du LM, Nurden P, Nurden AT, Nichols TC, Bellinger DA, Jensen ES, Haberichter SL, Merricks E, Raymer RA, Fang J, Koukouritaki SB, Jacobi PM, Hawkins TB, Cornetta K, Shi Q, & Wilcox DA (2013). Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A. Nature communications, 4 PMID: 24253479