Experimental gene therapy has been used to treat haemophilia A in dogs, with two of the three treated remaining free from serious symptoms after two years.
Haemophilia is a blood clotting disorder, most forms of which are inherited. There are many different sub-types of the disease, depending on which element of the normal blood clotting pathway is abnormal; haemophilia A is the most common form. It is an X-linked recessive disease, usually inherited and affecting primarily males, caused by Factor VIII deficiency. Worldwide, it affects around one in every 5,000 male births, and around one in every 10,000 adult men in the UK.
As most people with haemophilia require lifelong repeated injections of synthetic forms of the blood clotting factor they are deficient in, gene therapy is considered a desirable option, if only to reduce (rather than remove) the frequency of injections required. Previous clinical trials of gene therapy for haemophilia B in human patients have shown promising results, with two-thirds of recipients able to go without clotting factor treatment for significant periods (see previous news).
New research published in Nature Communications reports on a gene therapy trial in dogs with a disease similar to haemophilia A. Previous animal studies have shown potential for gene therapy targeted to the liver; in this instance researchers used a viral-based system to deliver copies the therapeutic gene (in this case a normal human factor VIII gene) to the bone marrow for expression in platelets, which play an important role in the normal blood clotting process. This would be a suitable strategy for use in haemophilia patients with liver damage, a substantial minority, for whom liver-targeted therapy would be unsuitable.
The approach successfully resulted in the production of normal factor VIII by platelets in response to blood vessel injury, with normal blood clotting. More than two years after the gene therapy, two of the three dogs treated remained free of any serious internal bleeding events; the third had received a lower dose of the gene therapy treatment and continued to need synthetic factor VIII to counter severe bleeds.
Commenting on this research, the UK’s Haemophilia Society said that they viewed gene therapy as a potential long-term solution and hoped to see it become available ‘on a 10-year horizon’ for haemophilia B, at least, and eventually haemophilia A too. However, they wisely cautioned that there was a long way to go from a small successful trial in dogs to clinical introduction of a safe and effective therapy for humans.