Haemophilia was recognised, though not named, in ancient times. In 1803, John Conrad Otto, a Philadelphia physician, was the first to publish an article recognising that a haemorrhagic bleeding disorder primarily affected men, and ran in certain families.
Dr. Schonlein, are credited with coining the term haemorrhaphilia for the condition in 1828 which was later shortened to haemophilia. Haemophilia is sometimes referred to as “the royal disease,” because it affected the royal families of England, Germany, Russia and Spain in the 19th and 20th centuries. Queen Victoria of England, who ruled from 1837-1901, is believed to have been the carrier of haemophilia B.
In the early 1900s, there was no way to store blood. People with haemophilia who needed a transfusion typically received fresh whole blood from a family member. Life expectancy was only c.13 years.
By the late 1950s and early 1960s fresh frozen plasma was transfused in patients in the hospital. However, each bag of the plasma contained so little of the necessary clotting factor that huge volumes of it had to be administered. At this stage, the life expectancy for a person with severe haemophilia was less than 20 years.
By the 1970s, freeze-dried powdered concentrates containing factor VIII and IX became available. Factor concentrates revolutionized haemophilia care because they could be stored at home, allowing patients to self-infuse factor products, alleviating trips to the hospital for treatment.
Treatment for haemophilia and other bleeding disorders advanced in the 1990s. Factor products became safer as tighter screening methods were implemented and advanced methods of viral inactivation were used. In addition, synthetic factor products were manufactured using recombinant technologies. In 1992, the first recombinant factor VIII product was approved by the FDA. In 1997, the first recombinant factor IX product was granted FDA approval.
The ultimate goal of gene therapy is the replacement of a defective gene sequence with a corrected version to eliminate disease for the lifetime of the patient. Between 1998 and 2001 five different Phase I clinical trials were initiated for the treatment of haemophilia by gene transfer. Several different gene delivery systems were used in these trials, including a retroviral vector, an adenoviral vector, two different adeno-associated viral vectors, and a non-viral gene delivery method.
In 2010, in collaboration with St Jude Children’s Research Hospital, Professor Amit Nathwani dosed his first haemophilia B patient using a gene therapy approach. This vector has shown very promising results and long-term follow up data have been published in the New England Journal of Medicine in 2011 and 2014.
Freeline Therapeutics was founded in 2015 focused on the development of liver directed gene therapies that have transformational potential for patients. Professor Amit Nathwani is the Chief Scientific Officer of Freeline Therapeutics and our therapies are based on our next-generation proprietary AAV vector platform, with the lead programme being a gene therapy to treat haemophilia B. The successes seen to date give us a solid platform for developing this gene transfer approach for the treatment of other conditions.
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Gene therapy has the potential to transform people's lives by safely and continuously delivering clotting proteins to the bloodLearn More >
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