Alprolix: Innovation in Treatment for Patients with Deficient or Dysfunctional Factor IX

Hemophilia is an X-linked recessive disease in which blood lacks blood-clotting proteins. Females have two X chromosomes, indicating that they are generally carriers and transmit the gene to their sons. People with mild hemophilia bleed after surgery, injury, or trauma. Severe hemophilia produces spontaneous internal bleeding in joints and muscles. Fortunately, medicines and lifestyle changes offers hemophiliacs fairly normal lives. Through learning about hemophilia, I became interested in genetic diseases and finding a cure for those

According to the National Hemophilia Foundation (n.d.), von Willebrand disease (VWD) is a genetic disorder caused by missing or defective von Willebrand factor (VWF), a clotting protein. VWF binds factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process. The condition is named after Finnish physician Erik von Willebrand, who first described it in the 1920s (National Hemophilia Foundation, n.d.). The seriousness of the bleeding varied between family

A mutation called an inversion is present which entirely changes the gene up to the point where it can't even make it which then causes the absence of the factor 8 protein. Symptoms include Severe or light bleeding due to the unstable clot which doesn’t do its job properly. Continuous bleeding will occur and can result in major complications of the joints, organs, brain, muscles, and others. In infants, bruising can be in effect all around the body after his/her first birthday, and bleeding(even from a tooth eruption). This is a sex-linked disease which effect about one in every four thousand or five thousand males no matter the ethnic group, but in females, it is even rarer. One of the people who came by this disease was Paul. Paul is from colorado and would always get injections from his own mom who was a nurse when he was an infant. He went to a Hemophilia camp in colorado and would practice injecting his treatment into practice objects so he could do it one day to himself. Paul said that he couldn’t really be apart of everyday life with people and the crowd because he always had to worry about the bleeding and hardships of

Each treatment should be treated case-by-case to ensure that the patient is receiving the best possible care. Suggested treatments consist of regular infusions of DDAVP and/or clotting factor, first aid for minor cuts, physical therapy, fibrin sealants and clot-preserving medications. For Hemophilia C, clotting factor XI is available only in Europe and in the United States bleeding episodes are treated through plasma infusions. Clotting factor XI is not available in the United States because Factor XI concentrates are blood products with a concentrated form of Factor XI. Meanwhile, available only in certain areas of Europe, these blood concentrates are made through a series combining thousands of different blood donors. Therefore, the United States only keeps frozen plasma instead. Fibrin sealants work by applying the medication directly to the site of the wound, from there the Fibrin promotes clotting and healing. Clot-preserving medications can also be applied directly to the wound. However, this time the medication preserves the clot from breaking down and assists in ending the

More patients are being started on factor Xa inhibitors due to their efficacy and safety profile compared to other agents, such as warfarin and enoxaparin. With the expanded use of these agents, there has come an increase in the occurrence of hospital admissions and deaths related to bleeding. It is estimated that in 2016, there were approximately 117,000 hospital admissions for bleeding caused by factor Xa inhibitors.1 Additionally, there were about 2,000 bleeding- related deaths per months.1 Up until May 2018, there was not an agent to reverse the effects of factor Xa inhibtors. In early May, the Food and Drug Administration (FDA) approved Andexxa, andexanet alfa, for the reversal of rivaroxaban and apixaban in the setting of life-threatening or uncontrolled bleeding.1

Currently there is no cure for hemophilia. But with clotting factor infusions and inclusion in support groups, most patients live full and relatively healthy lives. Scientist are always looking for a new cure according to La Kelley Communications (LA Kelley Communications, n.d), and they believe the answer lies in gene therapy. Potential treatment includes taking genes with the correct directions for making clotting factors and inserting them into the cells of a person with hemophilia. Scientists believe the new gene will give the correct directions to the body to start producing high levels of clotting factors, causing the person with hemophilia to develop successful blood

Hemophilia is the oldest known hereditary bleeding disorder. There are two types of hemophilia, A and B (Christmas Disease). Low levels or complete absence of a blood protein essential for clotting causes both. Patients with hemophilia A lack the blood clotting protein, factor VIII, and those with hemophilia B lack factor IX. A person with severe hemophilia has less than 1% of the normal amount of a clotting factor - either Factor VIII (8) or Factor IX (9). People without hemophilia have between 50-150% of the normal level of factor VIII or IX. There are about 20,000 hemophilia patients in the United States. Each year, about 400 babies are born with this disorder. Approximately 85% have hemophilia A and the remainder has hemophilia B.

This is because of the use of the intravenous infusion of factor VIII concentrate, home infusion programs, prophylactic treatment, and improved patient education.

Genetic therapy is a huge part towards bleeding disorders. Researchers claim that gene therapy is the next step to finding a permanent cure to this disorder. Research for improving coagulation factor levels is ongoing. Many patients with hemophilia are a bit worried with being a part of clinical trials involving new concentrates, especially in the United States. With new technology and new changes, it does bring some sort of uncertainty whether this can really work or how it can affect the patient in the long run (Ward et al, 2016). There have been cases where a man tried putting himself in a clinical trial, but later died due to complications. Like with any disease, one patient with hemophilia has a different case compared to another patient. So researchers are working on treating each patient individually, because some patients need more infusions of the coagulation factor compared to others, depending on their deficiency. Researchers have also found that “longer-acting products” should be used in clinical trials. These products which are essentially new factor concentrates can benefit children who are young, patients with phobias of needles, and those who exercise on a regular basis. Of course, this won’t benefit the entire hemophilia community, for example, those who have a mild severity of hemophilia, but it is definitely a step forward (Giangrande, 2016). It still remains unclear

The understanding of hemophilia has drastically improved over the last century. This has led to an improvement in the treatment of the disease. Despite this however, there has been little research in understanding how to prevent the transmission of the disease. The current understanding of the transmission of hemophilia greatly lags in comparison to the research poured into developing methods of gene therapy treatment.

(n.d.). Retrieved October 24, 2017, from https://medlineplus.gov/genesandgenetherapy.html#summary • Gene therapy for haemophilia. (1970, January 01). Retrieved October 24, 2017, from https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0069890 • https://www.gceguide.xyz/files/e-books/a-level/Cambridge%20International%20AS%20and%20A%20Level%20Biology%20Coursebook.pdf\ • Hacein-Bey-Abina, S., Kalle, C. V., Schmidt, M., Deist, F. L., Wulffraat, N., Mcintyre, E., . . . Fischer, A. (2003).

In addition to the Protalix ProCellEx platform, we can also incorporate features from similar plant production platforms that are being actively developed in publicly available research. The implementation of this technology can be used to synthesize recombinant coagulation factors for use in ClotX at a much higher yield-for-cost rate in addition to a substantially increased quality level. With the implementation of plant-based recombinant production, we have a considerable advantage over current market competitors that face difficulties in sustainability regarding cost.

Hemophilia is a blood disorder that’s usually genetically inherited from parents. People born with hemophilia have little or no clotting factor – a protein needed for normal blood clotting.

However there are 30% of cases are resulted from spontaneous mutation without any family history. Factor VIII deficiency (Haemophilia A) is the commonest type while incidence of Factor IX deficiency (Haemophilia B/ Christmas disease) is one fifth of it. Haemophilia is classified into 3 categories depending on the percentage of coagulation factor activity: severe (< 1%), moderate (2-5%) and mild (5-30%). Moderate and severe haemophilia has significant clinical manifestation as the patients have spontaneous bleeding especially into joint and

Occasionally a baby is born with this disorder and no family history of it. When this happens, it could be caused by a hidden gene, which is when several generations of female carry it, and it has not affected any male members of the family or a spontaneous mutation. With each pregnancy, a woman who is a carrier has a 25% possibility of having a son born with hemophilia. Since the father's X chromosome is what determines if the unborn child will be a girl, all of the daughters born of a man with hemophilia will be carriers. None of his sons, which is determined by the father through his Y chromosome, will have hemophilia. Individuals who suffer from mild hemophilia may choose to use a non-blood product known as Desmopressin acetate (DDAVP) to help treat the small bleeds and/or scrapes. For deep cuts or internal bleeding, the treatment called DDAVP may not be enough and therefore, may need a much more complex treatment. The clotting factor must be replenished so the affected person can form a clot to stop the bleeding. Plasma is one of the ‘human blood products’ than is used for factor replacement. Another factor replacement option is using the recombinant factor, which is produced in a laboratory.