Adeno-associated viral (AAV) gene transfer of coagulation factor IX to skeletal muscle and liver of murine and canine models of hemophilia has resulted in sustained systemic expression and, in several studies, in complete cure of the bleeding disorder.
Adeno-associated viral (AAV) gene transfer of coagulation factor VIII and IX to skeletal muscle and liver of murine and canine models of hemophilia A and B have resulted in sustained systemic expression and, in several studies, in complete cure of the bleeding disorder.
Despite the initial success of liver-directed adeno-associated virus (AAV) gene therapy for hemophilia in clinical trials, long-term sustained therapeutic effects have yet to be seen.
Adeno-associated virus (AAV) gene therapy vectors have shown the best outcomes in human clinical studies for the treatment of genetic diseases such as hemophilia.
Although the degree of scientific evidence of the publications on intra-articular injections of various drugs (hyaluronic acid, corticosteriods, PRP and MSCs) in haemophilia is very low, it seems that intra-articular injections of hyaluronic acid can relieve joint pain for months and can be repeated every 6-12 months, which is why they can be recommended.
We investigated the role of ABO blood groups in regulating FVIII immunogenicity by evaluating their distribution in patients with severe (FVIII < 1 IU/dL) HA according to inhibitor development and other known relevant factors.
In non-carriers, the association of FVIII with ABO blood groups was statistically significant (P = 0.006), but not in carriers of haemophilia A (P = 0.234).
Within the last decade more patients with severe haemophilia were switched to a prophylactic regimen going along with a moderate increase in factor consumption achieving a low ABR and AJBR.
Haemophilia type was not a significant predictor of ABR, target joints or HRQoL when adjusted for confounding factors such as BMI, age and replacement therapy regimen.
No significant subgroup differences in FIX:C values were found, thus suggesting the level of FIX:C concentrations in carriers to be unaffected by the severity of haemophilia, or by its expression (i.e. deficient or dysfunctional factor IX).
AHCDC: Association of Hemophilia Clinic Directors of Canada; AICE: Italian Association of Hemophilia Centres; ATHN: American Thrombosis and Hemostasis Network; EAHAD: European Association for Haemophilia and Allied Disorders; EHC: European Hemophilia Consortium; FIX: Coagulation Factor IX; FVIII: Coagulation Factor VIII; HAL: Haemophilia Activity List; HJHS: Haemophilia Joint Health Score; HTC: Hemophilia Treatment Centre; HTCCNC: Hemophilia Treatment Centre Collaborative Network of China; MASAC: Medical and Scientific Advisory Council; MDT: Multidisciplinary team; NHD: National Haemophilia Database; NHF: National Hemophilia Foundation; PK: Pharmacokinetics; POCUS: Point of care ultrasound; PWH: People with haemophilia; SHIELD: Supporting Hemophilia through International Education, Learning and Development; WFH: World Federation of Hemophilia.
To date, research in the field of gene therapy for haemophilia has largely relied on retroviruses, adenoviruses and adeno-associated viruses as transfer vectors and the major aims will be to achieve stable longlasting in vivo expression of factors VIII or IX (FVIII or FIX) at therapeutic levels.
Recombinant factor VII (rFVII) is the main therapeutic choice for hemophilia patients who have developed inhibitory antibodies against conventional treatments (FVIII and FIX).
Finally, difficulties in achieving tolerance after gene therapy for hemophilia A as compared to hemophilia B may relate to lower expression of FVIII than FIX, as high antigen levels are most effective at inducing tolerance.
Patients with haemophilia A (HA) or B (HB) experience spontaneous limb- or life-threatening bleedings which are prevented by regular prophylactic intravenous infusions of the deficient coagulation factor (FVIII or FIX).
von Willebrand disease (VWD) reflects a loss or dysfunction in von Willebrand factor (VWF), while haemophilia represents a loss or dysfunction of clotting factors such as factor VIII (FVIII) or FIX.
Haemophilia A and B diagnosis and disease severity classification are determined on the basis of results from factor VIII (FVIII) and factor FIX (FIX) activity assays, respectively.