ライフサイエンスコーパス: hemophilia A

1 is clotting factor to treat individuals with hemophilia A.

2 FVIII inhibitors, and patients with acquired hemophilia A.

3 s is the basis of modern treatment of severe hemophilia A.

4 (LV)-mediated human platelet gene therapy of hemophilia A.

5 y treated males aged >/=12 years with severe hemophilia A.

6 elet-derived FVIII can improve hemostasis in hemophilia A.

7 obulin G1 (IgG1) in 165 patients with severe hemophilia A.

8 mice of 2 different strain backgrounds with hemophilia A.

9 pic variability is well recognized in severe hemophilia A.

10 cement products enable comprehensive care in hemophilia A.

11 lso arise spontaneously in cases of acquired hemophilia A.

12 variability found among patients with severe hemophilia A.

13 ng previously untreated patients with severe hemophilia A.

14 nt impediment to the effective management of hemophilia A.

15 required to prevent bleeding associated with hemophilia A.

16 the importance of F8 genotyping in nonsevere hemophilia A.

17 ombinant) impair the effective management of hemophilia A.

18 152 patients (1-65 years of age) with severe hemophilia A.

19 he immune response to FVIII in patients with hemophilia A.

20 of F8 gene mutations in patients with severe hemophilia A.

21 al mechanisms and therapeutic development in hemophilia A.

22 on and less frequent dosing in patients with hemophilia A.

23 d by discrete cell populations would correct hemophilia A.

24 approach to reduce inhibitor development in hemophilia A.

25 factor VIII (FVIII) replacement therapy for hemophilia A.

26 l mechanism for secretion defects leading to hemophilia A.

27 rotein and gene transfer-based therapies for hemophilia A.

28 r VIII (fVIII) results in moderate to severe hemophilia A.

29 improve treatment options for patients with hemophilia A.

30 n to factor VIII (FVIII) in a mouse model of hemophilia A.

31 us for on-demand treatment for patients with hemophilia A.

32 y and may deliver effective gene therapy for hemophilia A.

33 n preclinical studies of novel therapies for hemophilia A.

34 ically appropriate gene addition therapy for hemophilia A.

35 icity--toward successful treatment of murine hemophilia A.

36 auses the human congenital bleeding disorder hemophilia A.

37 offers a potential gene therapy strategy for hemophilia A.

38 other hemorrhages in young boys with severe hemophilia A.

39 fective in treating bleeding associated with hemophilia A.

40 ng-term and safe treatment for patients with hemophilia A.

41 ion as a therapeutic option for persons with hemophilia A.

42 and could represent a curative treatment for hemophilia A.

43 issense mutations lead to moderate to severe hemophilia A.

44 es (inhibitors) is the major complication in hemophilia A.

45 VIII alloantibody formation in patients with hemophilia A.

46 III (AAV5-hFVIII-SQ) in nine men with severe hemophilia A.

47 the life-span among participants with severe hemophilia A.

48 outcomes with gene therapy in patients with hemophilia A.

49 potential use of ADHLSCs in the treatment of hemophilia A.

50 lating this strategy to clinical therapy for hemophilia A.

51 sent in inhibitor plasmas from patients with hemophilia A.

52 of previously untreated patients with severe hemophilia A.

53 ries is 30% for hemophilia A, 37% for severe hemophilia A, 24% for hemophilia B, and 27% for severe h

54 rities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cases for all severities of hemophilia

55 vantage for high-income countries is 30% for hemophilia A, 37% for severe hemophilia A, 24% for hemop

56 rities of hemophilia A, 9.5 cases for severe hemophilia A, 5.0 cases for all severities of hemophilia

57 0 males) is 17.1 cases for all severities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cas

58 0 males) is 24.6 cases for all severities of hemophilia A, 9.5 cases for severe hemophilia A, 5.0 cas

59 Hemophilia A, a bleeding disorder resulting from F8 muta

60 Hemophilia A, a deficiency of functional coagulation fac

61 Defects or deficiency of FVIII cause Hemophilia A, a mild to severe bleeding disorder.

62 early-phase study involving men with severe hemophilia A, a single intravenous injection of BIVV001

63 are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of pati

64 tuting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb

65 odies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are

66 Acquired hemophilia A (AHA) is an autoimmune disease caused by an

67 Acquired hemophilia A (AHA) is caused by autoantibodies against f

68 Acquired hemophilia A (AHA) is due to autoantibodies against coag

69 FVIII inhibitors, are the cause of acquired hemophilia A (AHA).

70 Hemophilia A, an X-linked bleeding disorder caused by de

71 tabases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these

72 At variance with hemophilia A and B and von Willebrand disease, RCDs are

73 Hemophilia A and B are caused by deficiencies in coagula

74 Hemophilia A and B are inherited bleeding disorders char

75 and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels.

76 Vector delivery via the portal vein in hemophilia A and B dogs was well tolerated, and long-ter

77 Treatment of patients with hemophilia A and B has undergone significant advances du

78 ARC19499 corrects thrombin generation in hemophilia A and B plasma and restores clotting in FVIII

79 ) activity and accelerates clotting of human hemophilia A and B plasma.

80 Hemophilia A and B, diseases caused by the lack of facto

81 ed bleeding disorders, including carriers of hemophilia A and B, or with von Willebrand disease, have

82 mmonest severe inherited bleeding disorders, hemophilia A and B.

83 has shown great promise for the treatment of hemophilia A and B.

84 d treatment of the prevalent bone defects in hemophilia A and B.

85 nt of inhibitory antibodies in patients with hemophilia A and discuss how these findings may be inter

86 Patients with severe hemophilia A and factor VIII inhibitors are at increased

87 ther bleeding events in patients with severe hemophilia A and factor VIII inhibitors.

88 elop this virus as a gene therapy vector for hemophilia A and familial hypercholesterolemia.

89 e tool, particularly in patients with severe hemophilia A and good risk profiles, and leads to a retu

90 New therapies for hemophilia A and hemophilia B will likely continue to ch

91 rtality did not differ significantly between hemophilia A and hemophilia B.

92 found in different cohorts of patients with hemophilia A and in healthy individuals.

93 II) antibodies that develop in patients with hemophilia A and in murine hemophilia A models, clinical

94 problems characteristic of individuals with hemophilias A and B suggest a link between specific defe

95 ents in intrinsic factor Xase function, i.e. hemophilias A and B, result in an impaired capacity to m

96 forts to extend AAV-mediated gene therapy to hemophilia A, and alternate approaches that may be usefu

97 ity criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor

98 on of AT levels in wild-type mice, mice with hemophilia A, and nonhuman primates (NHPs).

99 Treatment goals in severe hemophilia A are expanding beyond low annualized bleed r

100 acious prevention and treatment of bleeds in hemophilia A at reduced dosing frequency.

101 developed and tested our pipeline using the hemophilia A & B MIP design from the "My Life, Our Futur

102 tion and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled a

103 h sickle cell disease, beta-thalassemia, and hemophilia A/B or von Willebrand disease, respectively.

104 generate comparable curative fVIII levels in hemophilia A BALB/c mice after reduced-intensity total b

105 d in all United Kingdom patients with severe hemophilia A between 1990 and 2009.

106 normalize plasma FVIII level and activity in hemophilia A, but does not prevent the inhibitory effect

107 ns for the use of pFVIII in gene therapy for hemophilia A, but may also have physiologic consequences

108 ucts have improved the care of patients with hemophilia A, but the short half-life of these products

109 These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns af

110 tly change the treatment paradigm for severe hemophilia A by providing optimal protection against all

111 Conversely, individuals with hemophilia A caused by F8 missense mutations are CRM-pos

112 In severe hemophilia A, clot stability increased by > 4-fold in th

113 Most inhibitor patients with hemophilia A develop antibodies against the fVIII A2 and

114 Approximately 30% of patients with severe hemophilia A develop inhibitory anti-factor VIII (fVIII)

115 Absence of either factor leads to hemophilia, a disabling disorder marked by excessive hem

116 icacy in 2 global tests of hemostasis in the hemophilia A dog model indicate that further evaluation

117 hallenges with cFVIII-BDD in young and adult hemophilia A dogs did not induce the formation of neutra

118 to AAV-FVIII dogs and treatment-naive severe hemophilia A dogs for a multiweek dose-escalating period

119 Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of the disease

120 BOECs isolated from hemophilia A dogs transduced with this lentiviral vector

121 All 3 hemophilia A dogs treated with FVIII-expressing autologo

122 ficacy and safety in dogs with hemophilia A (hemophilia A dogs) with minimally increased hemostasis a

123 implanted into the omentum of 2 normal and 3 hemophilia A dogs.

124 ine FVIII (cFVIII) in 2 strains of inhibitor hemophilia A dogs.

125 gene transfer and in treatment-naive severe hemophilia A dogs.

126 Individuals with hemophilia A due to major deletions of the FVIII gene (F

127 cipants were >/=12 years of age, with severe hemophilia A (endogenous FVIII <1%).

128 ; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected

129 icles can be adapted to hemophilic patients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX d

130 bitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL).

131 aluated 574 consecutive patients with severe hemophilia A (factor VIII activity, <0.01 IU per millili

132 ated men (18 to 65 years of age) with severe hemophilia A (factor VIII activity, <1%) to receive a si

133 Near-to-complete correction of hemophilia A (factor VIII deficiency) and hemophilia B (

134 Black patients with hemophilia A (factor VIII deficiency) are twice as likel

135 nd biologic results in 15 adults with severe hemophilia A (factor VIII level, <=1 IU per deciliter) w

136 The risk for inhibitor development in mild hemophilia A (factor VIII levels between 5 and 40 U/dL)

137 factor VIII (FVIII) is used in patients with hemophilia A for treatment of bleeding episodes or for p

138 eotide repeat expansions in diseases such as hemophilia A, fragile X syndrome, Hunter syndrome, and F

139 econstruct HCV incidence in White males with hemophilia A from 1940 through 1990.

140 For this, we first generated hemophilia A (FVIII-/-) mice lacking EPCR (EPCR-/-FVIII-

141 ng without toxicity and translate success to hemophilia A gene therapy.

142 in general and have implication for ongoing hemophilia A gene-therapy clinical trials.

143 e can affect hemostasis in a canine model of hemophilia, a good predictor of efficacy of hemophilia t

144 Hemophilia A (HA) and hemophilia B (HB) are the most com

145 h acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C

146 I (hFVIII) were systematically evaluated for hemophilia A (HA) gene therapy.

147 Injection of FVIII-RH protein in hemophilia A (HA) mice resulted in more efficacious hemo

148 In the naive FVIII null hemophilia A (HA) mouse, platelet-derived VIII prevents

149 African American hemophilia A (HA) patients experience a higher incidence

150 factor VIII (FVIII) inhibitors seen in black hemophilia A (HA) patients is not due to a mismatch betw

151 e, elicits unwanted anti-FVIII antibodies in hemophilia A (HA) patients.

152 stematic analysis of missense mutations from hemophilia A (HA) patients.

153 for failure of FVIII replacement therapy in hemophilia A (HA) patients.

154 iously untreated patients (PUPs) with severe hemophilia A (HA).

155 endogenous factor VIII (FVIII) expression in hemophilia A (HA).

156 e seen in 25% to 30% of patients with severe hemophilia A (HA).

157 dies ("inhibitors") are a serious problem in hemophilia A (HA).

158 ed and novel approaches for the treatment of hemophilia A has expanded tremendously.

159 ors for replacement therapy of patients with hemophilia A has raised the life expectancy of these lif

160 vel recombinant FVIII (rFVIII) therapies for hemophilia A have been in clinical development, which ai

161 approximately 50% of individuals with severe hemophilia A) have been grouped with the former on the b

162 ansfer of a factor VIII (FVIII) plasmid into hemophilia A (HemA) mice achieved supraphysiologic FVIII

163 ately 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs.

164 e potential efficacy and safety in dogs with hemophilia A (hemophilia A dogs) with minimally increase

165 ts with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease.

166 in previously untreated patients with severe hemophilia A, high-dosed intensive FVIII treatment incre

167 taneous administration of AV513 to mice with hemophilia A improved hemostasis.

168 e very early phenotypic expression of severe hemophilia A in 621 consecutively enrolled, well-charact

169 a factor VIII concentrate for patients with hemophilia A including efficacy, availability, risk of t

170 od from F8-/-/PN-1-/- and from patients with hemophilia A incubated with a PN-1-neutralizing antibody

171 inhibitory Abs to factor VIII in people with hemophilia A indicate a complex process involving multip

172 y in previously treated subjects with severe hemophilia A investigated safety and pharmacokinetics of

173 Hemophilia A is a bleeding disorder caused by a deficien

174 Hemophilia A is a monogenic disease with a blood clottin

175 Acquired hemophilia A is a rare bleeding disorder caused by autoa

176 Acquired hemophilia A is a severe bleeding disorder caused by an

177 Hemophilia A is caused by a variety of mutations in the

178 Hemophilia A is caused by mutations in the gene encoding

179 Hemophilia A is caused by mutations within the Factor VI

180 proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of facto

181 nsequences and result in a potential "cure." Hemophilia A is often complicated by the development of

182 t complication of treatment in patients with hemophilia A is the development of alloantibodies that i

183 n complication of treatment of patients with hemophilia A is the development of anti-factor VIII (fVI

184 with severe cases of congenital or acquired hemophilia A is the development of inhibitor antibodies

185 Inhibitor formation in hemophilia A is the most feared treatment-related compli

186 Hemophilia A is the X-linked bleeding disorder caused by

187 or previously untreated children with severe hemophilia A, it is unclear whether the type of factor V

188 actor VIII was administered i.v. to neonatal hemophilia A knockout mice.

189 ibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for repl

190 factor VIII (hFVIII) plasmid gene therapy in hemophilia A mice also leads to strong humoral responses

191 olerance to hFVIII in hFVIII plasmid-treated hemophilia A mice and allowed persistent, high-level FVI

192 olerance in syngeneic hFVIII plasmid-treated hemophilia A mice and reduced the production of antibodi

193 blood outgrowth endothelial cells (BOECs) to hemophilia A mice and showed that these cells remained s

194 ious times after transplantation (7-90 days) hemophilia A mice and their control mice counterparts we

195 or VIII (fVIII) C2 domain immune response in hemophilia A mice consists of antibodies that can be div

196 Nontransplanted hemophilia A mice died within a few hours, whereas trans

197 lasma FVIII levels increased in transplanted hemophilia A mice during this period to 8% to 12% of wil

198 -type mice through 50 weeks, while untreated hemophilia A mice exhibited no detectable FVIII activity

199 derived mesenchymal stromal cells, protected hemophilia A mice from bleeding challenge with appearanc

200 r 8 (F8) in platelets improves hemostasis in hemophilia A mice in several injury models.

201 ower expression levels relative to mFVIIa in hemophilia A mice or in hemophilia B mice with inhibitor

202 urther, plasma FVIII activity in the treated hemophilia A mice was nearly identical to that in wild-t

203 tg+/-) BM cells still improved hemostasis in hemophilia A mice with inhibitors.

204 responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized

205 2bF8) gene therapy can improve hemostasis in hemophilia A mice, even in the presence of inhibitory an

206 MAbs were injected into hemophilia A mice, followed by injection of human B doma

207 ssion in platelets can restore hemostasis in hemophilia A mice, this approach has not been studied in

208 acute and prolonged vascular injury model in hemophilia A mice.

209 FVIII by transplanting healthy mouse BM into hemophilia A mice.

210 apsules and injected them intravenously into hemophilia A mice.

211 existing anti-FVIII inhibitory antibodies in hemophilia A mice.

212 jected directly into the liver of irradiated hemophilia A mice.

213 ody formation, and improved the phenotype of hemophilia A mice.

214 m, we sought to recapitulate its efficacy in hemophilia A mice.

215 c levels of FVIII gene expression in treated hemophilia A mice.

216 2 monoclonal Abs (mAbs) produced in a murine hemophilia A model.

217 in patients with hemophilia A and in murine hemophilia A models, clinically termed "inhibitors," bin

218 Ferriere et al present an emicizumab-adapted hemophilia A mouse bleeding model that can help answer t

219 equences provides curative fVIII levels in a hemophilia A mouse model.

220 ease fVIII clearance and are pathogenic in a hemophilia A mouse tail snip bleeding model.

221 therapy can be lifesaving for patients with hemophilia A, neutralizing alloantibodies to FVIII, know

222 study presents mortality in 6018 people with hemophilia A or B in the United Kingdom during 1977 to 1

223 d 4 through 18 years with moderate or severe hemophilia A or B were monitored for bleeds for up to 1

224 and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibo

225 sed thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibo

226 in phase 1 clinical testing in subjects with hemophilia A or B.

227 s, and the wave did not form in plasmas from hemophilia A or C patients who lack factors VIII and XI,

228 potency of ADHLSCs to control bleeding in a hemophilia A patient and assess the biodistribution of t

229 I-binding antibodies in different cohorts of hemophilia A patients and in healthy individuals.

230 The presence of antibodies (Abs) in hemophilia A patients can potentially influence the ther

231 This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Aust

232 ompetence and inhibitor status by evaluating hemophilia A patients harboring F8-null mutations that w

233 evaluation of AV513 as a hemostatic agent in hemophilia A patients is warranted.

234 ve and 174 inhibitor-negative Italian severe hemophilia A patients using a TaqMan genotyping assay.

235 on that affects approximately one-quarter of hemophilia A patients who have access to replacement the

236 creased incidence of anti-drug antibodies in hemophilia A patients with haplotypes H3 and H4.

237 approach for future tolerogenic treatment of hemophilia A patients with inhibitors.

238 A major problem in treating hemophilia A patients with therapeutic factor VIII (FVII

239 o FVIII is a serious problem in treatment of hemophilia A patients, we investigated the potential of

240 anti-FVIII inhibitory antibody formation in hemophilia A patients.

241 r complication in the replacement therapy of hemophilia A patients.

242 ctor VIII replacement therapy for congenital hemophilia A patients.

243 inhibitors and could improve the outcomes of hemophilia A patients.

244 7 to 13 days (at 35 IU/kg rFVIII) in severe hemophilia A patients.

245 may be useful for therapeutic management of hemophilia A patients.

246 erties show high interpatient variability in hemophilia A patients.

247 I PK profile in a population of 43 pediatric hemophilia A patients.

248 O variants that modify FVIII PK in pediatric hemophilia A patients.

249 specific IgG to FVIII half-life reduction in hemophilia A patients.

250 responses, including inhibitor responses in hemophilia A patients.

251 to 8% to 12% of wild type and corrected the hemophilia A phenotype.

252 ependent prolongation of clot lysis times in hemophilia A plasma and loss of TM-stimulated conversion

253 bin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which p

254 ects were compared with 4 inhibitor-positive hemophilia A plasma samples with inhibitor titers of 1 B

255 lot lysis assay on TM-expressing cells using hemophilia A plasma, NAc-Hep prevented PF4-mediated inhi

256 untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe

257 velopment was investigated in all 407 severe hemophilia A previously untreated patients born in the U

258 Among 235 randomized patients with severe hemophilia A previously untreated with FVIII concentrate

259 different categories of patients with severe hemophilia A: previously untreated patients, multiply tr

260 VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding patter

261 ne tolerance induction(ITI) in patients with hemophilia A refractory to replacement therapy after the

262 Patients with hemophilia A rely on exogenous factor VIII to prevent bl

263 ver, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the ra

264 h AAV5-hFVIII-SQ vector in participants with hemophilia A resulted in sustained, clinically relevant

265 r prophylaxis and treatment of patients with hemophilia A. rFVIIIFc is a recombinant fusion protein c

266 c epitope in FVIII were isolated from a mild hemophilia A subject (the proband) 19 weeks and 21 month

267 recombinant T-cell receptor obtained from a hemophilia A subject's T-cell clone, into expanded human

268 binant T-cell receptor (TCR) isolated from a hemophilia A subject's T-cell clone.

269 purified human anti-fVIIIAb, isolated from a hemophilia A subject, was used as a calibrator with a de

270 150 healthy donors and 39 inhibitor-negative hemophilia A subjects were compared with 4 inhibitor-pos

271 M, whereas 13 (33%) of the 39 inhibitor-free hemophilia A subjects were positive for anti-fVIIIAb in

272 115 "good-risk," severe high-titer inhibitor hemophilia A subjects.

273 the FVIII variant K1967I is associated with hemophilia A, suggests that these residues contribute to

274 man use of a new nonsubstitutive therapy for hemophilia A that can potentially be disruptive to the w

275 In a mouse model of hemophilia A, the complex normalized hemostasis upon vas

276 In hemophilia A, the most severe complication of factor VII

277 non-FVIII alternative to reduce bleeding in hemophilia A, the question of how much clotting is enoug

278 eas substitution of FVIII is the mainstay of hemophilia A therapy, treatment of patients with inhibit

279 minates how inhibitory antibodies complicate hemophilia A therapy.

280 Therefore, BM transplantation corrected hemophilia A through donor-derived mononuclear cells and

281 actor VIII inhibitors arise in patients with hemophilia A throughout life with a bimodal risk, being

282 factor VIII gene (F8) in black patients with hemophilia A to identify causative mutations and the bac

283 We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor

284 actor VIII (FVIII), the protein deficient in hemophilia A, to elucidate the relationship between prot

285 antibody emicizumab is increasingly used for hemophilia A treatment.

286 its by diminishing bleeding complications in hemophilia A via restoration of TAFIa-mediated protectio

287 A patient suffering from hemophilia A was injected with repeated doses of ADHLSCs

288 nhibitor development in patients with severe hemophilia A, we applied whole-exome sequencing (WES) an

289 g this strategy into the canine (c) model of hemophilia A, we increased cFVIII transgene expression b

290 Nine dogs with hemophilia A were treated with adeno-associated viral (A

291 pment of liver-directed AAV gene therapy for hemophilia A, while emphasizing the importance of long-t

292 ciation study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with hum

293 e of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII co

294 We enrolled patients with hemophilia A who were older than 2 years of age, had hig

295 ealthy individuals, patients with congenital hemophilia A with and without FVIII inhibitors, and pati

296 roved thrombin generation in an NHP model of hemophilia A with anti-factor VIII inhibitors.

297 epopulation of the livers of mice that model hemophilia A with healthy endothelial cells restored pla

298 f 42 adult patients with severe and moderate hemophilia A without inhibitors.

299 Gene therapy for hemophilia A would be facilitated by development of smal

300 or VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment optio