Adeno-associated virus as a delivery vector for gene therapy of human diseases
Children's Hospital Administers First Commercially Available Gene Therapy For Hemophilia B
Children's Hospital of Michigan in Detroit has administered Michigan's first commercially available gene therapy for hemophilia B to a 26-year-old Wyandotte man. // Stock photoA 26-year-old Downriver man seen at Children's Hospital of Michigan in Detroit since infancy for a rare bleeding disorder in July became the first person in Michigan to receive an FDA-approved, commercially available gene therapy for hemophilia B.
"It is a privilege to be part of this historic advancement, and I look forward to continuing our efforts to bring transformative therapies to our patients and families," says Dr. Madhvi Rajpurkar, division chief of hematology at Children's Hospital.
The Wyandotte man's treatment at Children's Hospital of Michigan's Hematology Center could help end his life-long dependency on medical infusions and avoid critically dangerous bleeding episodes.
"As a child, his family had to advocate for him and he had to learn from an early age to advocate for himself," says Dr. Bulent Ozgonenel, who has been the patient's hematologist for several years and was instrumental with Children's Hospital social worker Rachel Cain-Kellman in evaluating and preparing the patient for gene therapy.
"If he fell or was playing when he was young, or in an activity that any one of us takes for granted, the resulting bleeding could cause him to not walk well, or it could be life-threatening. This advancement in medical science could be life-altering for him."
Hemophilia patients' blood lacks a protein — Factor IX, or Factor 9 — that helps with clotting. This genetic mutation, often passed down through families, puts them at risk for spontaneous bleeding, internally or externally, and they can suffer life-threatening bleeding if injured.
Until now, the only treatment for hemophilia has been regular infusions of clotting factor, sometimes multiple times a week, to prevent bleeding from injuries related to things like sports or other physical activity, bumps, bruises or cuts. The Children's Hospital patient had undergone infusions since he was an infant, and he was self-administering infusions three times a week before the hour-long July procedure.
"He said he has wanted to get gene therapy since he was 15, but it was only available in trials," says Charity Stadler, Hemophilia Treatment Center director of nursing at Children's Hospital, part of the team who helped start the hemophilia gene therapy program at hospital. "We're very happy to be the first center to provide this treatment commercially in Michigan. This is definitely a revolutionary treatment. We're hoping the very best for him."
The gene therapy the man received, HEMGENIX produced by CSL Behring and administered by Children's Hospital Nurse Coordinator Michelle Hyde, could end his infusions completely. The new genes introduced are designed to help the patient's liver produce the blood clotting agent that was lacking: Factor 9. He will visit the Children's Hospital team weekly for testing to ensure his liver continues to function well, his Factor 9 level is rising, and he is not experiencing symptoms of bleeding.
"Congratulations to Children's Hospital of Michigan on becoming the first institution in the state to commercially administer HEMGENIX," says Diego Sacristan, senior vice president, U.S. At CSL Behring. "We're proud to see this important innovation reaching patients and advancing care."
Success is achieved when the patient's Factor 9 level reaches 10 percent — 50 percent is a sufficient level for most people — and his blood has enough clotting factor to end the prophylactic infusions. After three months, he will be tested monthly, then annually if his first year of monitoring goes well. The only time he will potentially need an infusion to aid clotting is if he suffers an injury.
"This is a game-changer for many patients — young and old," says Archie Drake, CEO of Children's Hospital of Michigan. "From being able to enjoy everything from outdoor activities to cooking — where cuts could be a threat — we are so pleased this has the potential to offer freedom and a sense of normalcy to this patient and potentially many others with hemophilia. The Children's Hospital of Michigan has a long history of offering life-altering treatments, and this is another wonderful opportunity for our patients."
Rajpurkar says she's proud to be part of a long history of bleeding disorder care for patients at Children's Hospital of Michigan. She notes that the Jeanne M. Lusher Center for Hemostasis and Thrombosis is named after one of her mentors, Dr. Jeanne M. Lusher, a researcher in the field of blood disorders and director of the Hemostasis Program at the Children's Hospital of Michigan until she retired in 2013. Rajpurkar also credits Children's Hospital of Michigan bleeding disorder pioneer Dr. Indira Warrier as a leader in the field.
"This milestone honors the legacies of Drs. Lusher and Warrier, who shaped my approach to hemophilia care with their unwavering commitment to excellence, compassion and patient-centered innovation," Rajpurkar said. "I am grateful for the foundation they laid and proud to carry forward their work here at Children's Hospital of Michigan — a place where generations of children with bleeding disorders have received world-class care."
Treatment Of Hemophilia B - Everyday Health
Standard treatment for hemophilia B involves replacing the missing clotting factor so that the blood can clot properly. This is called factor 9 replacement therapy. The two main replacement therapies are plasma-derived factor concentrates and recombinant factor concentrates, which are infused into the bloodstream via a vein in the arm.
In both cases, infusions of the concentrates are done prophylactically, meaning they're done on a regular basis to prevent bleeding episodes, according to the Centers for Disease Control and Prevention (CDC).[7] However, if you have severe hemophilia B, you may also need to take a factor 9 concentrate before surgery or dental work, according to MedlinePlus.
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People who have hemophilia usually learn to self-administer their replacement therapy at home. In fact the National Bleeding Disorders Foundation (NBDF) has self-infusion instructions for kids who are mature enough to learn how to infuse their own factor.[8]
The cost of factor 9 replacement therapy is significant. The NBDF states that the average annual cost of clotting factor therapies for a person with severe hemophilia is roughly $300,000, and overall yearly medical expenses can be twice that.[9]
Plasma-Derived Factor 9 ConcentratesPlasma-derived factor 9 concentrates are derived from human donations of blood or plasma.
The liquid part of blood, called plasma, contains clotting factors and other proteins, such as antibodies and albumin, according to the CDC.[7] Albumin is a protein made by your liver to help keep fluid from leaking out of your blood vessels, according to MedlinePlus.
[10]
All donated blood or plasma go through tests for viruses. The plasma goes through multiple processes to separate it into components, such as clotting factors. The clotting factors are freeze-dried and treated to kill (or make inactive) any viruses found, according to the CDC.
Two plasma-derived factor 9 concentrates are available in the United States:
[11]
[12] These products are developed in the lab using DNA technology. Recombinant factor 9 concentrates are not able to spread bloodborne viruses, because they are synthetic and not from humans, according to the CDC.
Available recombinant factor 9 concentrates include:
[13]
[14]
What To Know About Hemophilia B - Medical News Today
Hemophilia B, also known as Christmas disease, is a bleeding disorder. Its characteristic feature is a deficiency of clotting factor IX. This is a protein present in the blood that helps with coagulation, or clotting.
Hemophilia describes a group of bleeding disorders where blood is unable to clot properly. This occurs due to a deficiency in certain proteins known as clotting factors. Many different clotting factors play a different role in the coagulation cascade.
The coagulation cascade refers to a series of steps that occur in response to bleeding. The process involves clotting factors, and the series of reactions ultimately leads to the formation of a blood clot. A deficiency in a clotting factor impairs this process and can result in spontaneous bleeding or severe bleeding following an injury.
A note about sex and genderSex and gender exist on spectrums. This article will use the terms "male," "female," or both to refer to sex assigned at birth. Learn more.
Hemophilia B primarily occurs due to a genetic variation in the F9 gene, which is present on the X chromosome. This is why medical professionals may describe hemophilia B as an X-linked condition.
The F9 gene is responsible for producing factor IX. As such, this gene alteration results in a deficiency, or impaired function, of clotting factor IX.
Clotting factor IX is one of the many clotting factors that play a crucial role in the blood clotting cascade. Without sufficient levels of factor IX, a person will experience difficulties forming blood clots and is susceptible to prolonged bleeding.
In most cases, people inherit the gene alteration for hemophilia B from a parent. However, in extremely rare cases, a person may develop acquired hemophilia B. This type of hemophilia is not present at birth — instead, an individual develops the condition later in life.
Acquired hemophilia B occurs when the body mistakenly produces antibodies against factor IX. The factor IX antibodies then destroy any circulating factor IX in the blood, resulting in the bleeding symptoms of hemophilia.
Hemophilia is a group of conditions that occur due to problems with clotting factors. There are multiple clotting factors and different types of hemophilia, which correspond to deficiencies of different clotting factors.
Hemophilia A is the most common type of hemophilia. Its characteristic feature is a deficiency of factor VIII due to variations in the F8 gene. Hemophilia C is also distinct from hemophilia B, as it instead occurs due to alterations in the F11 gene and affects clotting factor XI. There are also less common conditions that affect other blood clotting factors.
Hemophilia conditions typically share similar symptoms and treatment approaches but result from variations in different genes that affect different clotting factors.
Similar to other types of hemophilia, hemophilia B is an inherited bleeding disorder primarily affecting males. Evidence notes that the prevalence of hemophilia B is roughly 1 in 40,000 live males. This accounts for about 15% of cases of hemophilia.
Hemophilia B is typically a congenital condition, meaning people are born with it. In most cases, a person inherits the condition from a parent.
The F9 gene is present on the X chromosome. A male will usually inherit one X chromosome from a female parent, while females typically inherit an X chromosome from both parents. As such, males usually only require one gene alteration to develop the condition, which is why it is more common in males.
While much rarer, hemophilia can also affect females. They will typically require either two X chromosome alterations, or one with a variation and the other X chromosome is missing or nonfunctioning.
Evidence also notes that roughly 10–25% of female carriers for hemophilia B may also experience symptoms of the condition. Hemophilia B also affects all races and ethnic groups equally.
Some people may also refer to hemophilia B as the royal disease due to being prevalent in the royal families of England, Spain, Germany, and Russia.
The characteristic symptom of hemophilia is issues with blood clotting. This makes people with the condition more susceptible to prolonged periods of bleeding.
The severity of hemophilia B can range from mild to severe. The severity depends on the level of factor IX present in the blood. Symptoms of hemophilia B can include:
Severe hemophilia B
This describes a person with less than 1% clotting activity. They may experience:
Moderate hemophilia B
This typically refers to individuals with 1–5% clotting factor activity. Symptoms may include:
Mild hemophilia B
Mild hemophilia B usually describes factor activity between 5% and 40%. People may experience:
Similar to treating other types of hemophilia, the primary treatment option for hemophilia B involves replacing factor IX. A person will usually receive replacement therapy through regular intravenous infusions through a vein in the arm or a port in the chest.
Before surgery or dental procedures, a doctor may also recommend aminocaproic acid. It is an antifibrinolytic, which means it prevents the breakdown of blood clots. As such, it may help to preserve a blood clot and keep it from breaking down prematurely.
After injecting Hemgenix into a person's vein, the virus travels to the liver, which allows the liver cells to produce factor IX and limit bleeding episodes.
Hemophilia B is a bleeding disorder. It typically occurs due to a variation in the F9 gene, which a person inherits from their parents.
Alterations in the F9 gene affect the production of clotting factor IX. This protein plays an important role in the formation of blood clots. Without sufficient levels of factor IX, a person is susceptible to long bleeding episodes.
Hemophilia B can vary in severity, depending on the levels present in the blood. Treatment for hemophilia B usually involves replacing the deficient factor IX to help with blood clotting and prevent excessive bleeding.
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