Even blue blood can be imperfect

26 July 2017 | BioPharm

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It’s not widely known that haemophilia was quite common amongst the royal families of Europe during 19th and 20th centuries. In fact, it was once referred to as the ‘Royal Disease’. From Britain’s Queen Victoria, through two of her five daughters (the Princesses Alice and Beatrice), haemophilia was passed to various royal houses across the continent, including those of Spain and Germany. Victoria’s son Prince Leopold, Duke of Albany, also suffered from haemophilia, and tests on the remains of the Romanov imperial family showed that the Royal Disease had reached as far as Russia.


What happens when people lack factor VIII or factor IX?

Most of us will have experienced the fact that if we cut ourselves we bleed. Most of us will also have experienced our blood’s smart ability to clot to stop the bleeding, such that we now take that process for granted.

But what happens if the substances in our blood – known as clotting factors – are lacking so they’re not available to combine with blood cells called platelets to make our blood sticky and clot? The result is haemophilia and the two main types are caused by a deficiency of one of two proteins – a lack of factor VIII causes haemophilia A, while a lack of factor IX causes haemophilia B. The latter is also known as the Christmas factor, its name taken from the surname of the first boy discovered to be lacking it when haemophilia B was first identified in 1952.


How common is haemophilia?

Haemophilia is inherited, passed to a child by one or both of their parents but usually down the male line. While there are about 6,000 people with haemophilia in the UK, it’s a global problem. Worldwide, it’s estimated that one boy in every 5,000 will be born with haemophilia A and one in every 30,000 with haemophilia B.

Haemophiliacs can bleed longer, especially after surgery or an injury, bruise more easily, and suffer from an increased risk of bleeding inside joints or the brain. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a decreased level of consciousness. This disease can be life-threatening and in women it can cause complications around menstruation and childbirth.

“Freeline’s therapies, delivered in one single treatment, have the potential to provide long-term benefits to patients by carrying a therapeutic gene to target cells in the body, allowing more cells to then express therapeutic proteins for the body”

New hope for haemophiliacs

Although treatments have improved in recent years, through, for example, prophylactic injections of the missing factor, in past decades patients had to rely on transfusions. This left them vulnerable to infectious diseases, such as hepatitis B in the ’70s, HIV in the ’80s and hepatitis C in the ’90s.

However, that has all changed with a pioneering new gene therapy treatment developed by Professor Amit Nathwani, Professor of Haematology at UCL and Director of the Katharine Dormandy Haemophilia Centre and Thrombosis Unit of Royal Free London NHS Foundation Trust.

Indeed, this innovative gene therapy has already begun to transform lives by providing a safe, reliable source of the blood clotting protein factor IX. A successful haemophilia B phase I/II trial conducted by Professor Nathwani at UCL in collaboration with St. Jude Children’s Research Hospital, Memphis, demonstrated that all treated haemophilia B patients on the trial showed safe, sustained expression of blood clotting factor IX from a single treatment, according to results published in the New England Journal of Medicine.

The Professor is also founder and Chief Scientific Officer (CSO) of a new company – Freeline Therapeutics – their lead programme is a factor IX gene therapy programme. Launched in December 2015 by Syncona LLP and UCLB, Freeline Therapeutics is based at the Royal Free Hospital in London. Their mission is to become a leading biopharmaceutical company for the successful development and commercialisation of liver-directed gene therapies for bleeding disorders and other severe diseases.

A single treatment, long term benefits

Freeline’s therapies, delivered in one single treatment, have the potential to provide long-term benefits to patients by carrying a therapeutic gene to a target cell in the body. These therapies are based on the company’s next-generation proprietary adeno-associated virus (AAV) vector platform.

Freeline’s lead programme is the gene therapy to treat haemophilia B, which is expected to be in clinics by late 2017.

Professor Nathwani commented, ‘Our initial study has shown the potential of AAV gene therapy. Freeline will bring industry-leading development people and our expertise together to ensure our clinical translation is rapidly converted to registered therapeutics.’

Cengiz Tarhan, Managing Director of UCLB, added, ‘UCL is a world leader in the biomedical sciences, with a commitment to outstanding research and translation into healthcare benefits for patients. I am pleased that Professor Nathwani’s work is being taken forward in a commercial environment in a way that may benefit patients globally. UCLB are delighted to be able to partner with Syncona to launch the company.’