Evaluation Of Type 1 Gaucher Disease Patients Treated Ith Imiglucerase

1,639 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,639
On SlideShare
0
From Embeds
0
Number of Embeds
5
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Evaluation Of Type 1 Gaucher Disease Patients Treated Ith Imiglucerase

  1. 1. EVOLUTION OF TYPE 1 GAUCHER DISEASE PATIENTS TREATED WITH IMIGLUCERASE Paula Grigorescu-Sido1) , Camelia Al-Khzouz 1) , Cristina Drugan 2), Simona Bucerzan 1) , Cristina Coldea 1) 1)Genetic Diseases Center –Emergency Children Hospital , First Pediatric Clinic Cluj 2) Biochemistry Department of University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj
  2. 2. Gaucher Disease - monogenic disease – AR - glucocerebrosidase deficiency - types: 1 nonneuronopathic (92%)*) 2 with neurological (1%)*) 3 involvement (7%)*) *) Gaucher Registry/2007
  3. 3. ● Genetics - 1q.21 - genomic region - 32 kilobases - active gene 7,6 kb > 200 mutations -pointmutations !! (11 exons) - insertions - deletions - pseudogene 5,6 kb - 2 pointmutations - deletions - AR - homozygote - composed heterozygote
  4. 4. Glucosyl-ceramide (glucocerebroside) creamed glucosyl Glucocerebrosidase - lysosomale enzyme (acid β-glucosidase (acid-hydrolase – pH=5) Glucose ceramide
  5. 5. Gaucher Cell
  6. 6. Multisystemic pattern Monocytes Bone Spleen Marrow Macrophages Tissue Macrophages Liver Lung Bone Kupffer Cells (Hepatocytes Spared) Alveolar Osteoclasts Macrophages
  7. 7. Epidemiology: - panethnical pattern: 1/40.0001) 1/50.0002) 1/200.0003) 1/100.0004) - Ashkenazi jews: - 1/500 - 1/1.000 n.b. alive - 25-30.000 patients all over the world - 4.272 - Gaucher Registry 2005 - ≈ 3/4 - on enzyme therapy - Meha A Eur J Inte Med,2006,17:S2- 5 - Germain D.P. Hématologie 1999, 5: 480-493 3) Grabowski G.A. Gaucher Disease: diagnosis, evaluation and treatment. Gardiner-Caldwell Syner-Med, New Jersey 1994 3) Stirnemann J. et al. La maladie de Gaucher; Encyclopedie Orphanet, 2004
  8. 8. Clinical features in type 1 Gaucher disease Organ enlargement - splenomegaly - hepatomegaly Hematological findings: - trombocytopenia - anemia - leucopenia Osteopathy: - pain chronic acute - “bone crisis” - fractures -bone deformities Chronic respiratory failure. Growth retardation and puberty delay1) (♀)
  9. 9. Enzyme replacement therapy Preparations Obtaining Trade name Pharmaceutical method company Alglucerase’) Extracted from Ceredase Genzyme studys:1970-1982)**) placenta (FDA:1991) (risk – prionic disease ?) Imiglucerase’) recombinant Cerezyme Genzyme (FDA:1994) DNA technology vials of 200 UI*) 400 UI *) changed inorder to expose manosic residures of lateral oligosaccharidic chains → binding to manoso-P receptors on the cell membranes of macrophages → “targeted” enzyme therapy! R.O.Brady National Institutes of Health, Peter Pentchev –
  10. 10. In Romania - specific diagnosis ..................................1997 - enzyme replacement therapy ………....2002 (sporadically) ....2004 Genetic Diseases Center –Emergency Children Clinical Hospital, First Pediatric Clinic Cluj – Biochemistry Department of University of Medicine and Pharmacy “Iuliu Hatieganu”Cluj (Conf.Dr.Cristina Drugan)
  11. 11. Aim of the study • Assessment of clinical outcome in Gaucher patients with enzyme replacement therapy
  12. 12. Matherial: - 32/50 type 1 Gaucher patients who received ERT (22 females and 10 males) age 28,4+/-12,1 ys
  13. 13. Treatment: Cerezyme (imiglucerase) - 30-60 U/kgc (45,4 + 13,6 U/kg/infusion) - i.v. infusion - every 2 weeks - 0,25-6,5 years (3,1 ± 1,4 years)
  14. 14. ● Monitoring: - Parametres: - Hb - thrombocyte countat at baseline and - spleen volum - ultrasound assessment - liver volum - chitotriosidase - radiograms - osteodensitometry - severity score (Zimran) - - body weight 6 ± 2 months treated - heigth (children) 6-12 months untreated *) xN (N=0,2% patients weight) 1) Weinreb N.Y. et al., Am J Med, 2002,113:112-119. **)xN (N=2,5% patients weight) 2) Hollak C.E. et al. J.Clin.Invest., 1994,93:1288-1292.
  15. 15. RESULTS
  16. 16. Progression of hemoglobin in patients with anemia on Cerezyme therapy *) (n=11/32: 34,3%; 3 –splenectomised patients ) Hb (g/dl) X 15 9,5± 12,3± 13,5± 13± 12,8± 13± 12,8± 12,8 ± 12,8± 13,6± 10 5 11 11 11 11 9 8 8 8 6 4 0 0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 years 1) 35% - Registrul Gaucher 2006 *) ~ Weinreb N.J. et al., Am. J. Med. 2002, 113
  17. 17. Progression of thrombocyte count in patients on Cerezyme therapy *) (n=22/32: 68,6%; 1 p –splenectomised patient) Tr/mmc X 180000 168333 160944 163071 160000 151681 154444 151000 141318 140000 121318 120000 100000 76045 80000 60000 22 22 22 22 18 18 14 13 12 40000 20000 0 0 0,5 1 1,5 2 2,5 3 3,5 4 years *) ~ Weinreb N.J. et al., Am. J. Med. 2002, 113
  18. 18. Regression of spleen volume on treatment (xN) (n=21: 100%) Spleen volume (xN) 16 14,4 14 12 10,9 10 8 8 5,9 6 5 4,5 3,8 3,4 4 3 2 21 21 21 21 18 17 13 12 11 0 0 0,5 1 1,5 2 2,5 3 3,5 4 years *) Weinreb N.J. et al., Am. J. Med. 2002, 113 (50-60% în 2-5 ani)
  19. 19. Regression of liver volume on treatment (xN) (n=28/32: 88%) Liver volume (xN) 1,6 1,5 1,4 1,2 1,2 1,1 1,1 1,06 1,03 1,02 1,01 1 1 1,02 1 0,8 0,6 0,4 28 28 28 28 26 25 23 22 18 5 3 0,2 0 0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 years Weinreb N.J. et al., Am. J. Med. 2002, 113 (30-40% în 2-5 *) ani ↓)
  20. 20. • Bone disease : 1) Clinically: At onset At present Chronic pain: 30 patients (96,8%) significantly improved 21 patients (66,6%) Bone crises: 6 patients -2 patients Fractures: 4 patients 1 patient (Male) ( after 6 years ERT) + 1 patient ( Female) (after 4 years ert)
  21. 21. Assessment of bone mineral density according to lumbar column Z score (DXA) (n=20 patients) 100% 65% 80% 60% 40% 35% 35% 30% 20% 6p 7p 7p 0% Improvement Stationary Aggravation - Cerezyme 30U/kg ... 6p - climax .......................1p - late start of the ERT
  22. 22. Chitotriosidase level on treatment (n=31) nmol/h/ml plasmă X 45000 39548 40000 35000 30000 25000 22946 20000 16414 15000 8416 7184 9923 10000 4563 4517 3802 5000 31 31 31 31 28 26 22 21 17 0 0 0,5 1 1,5 2 2,5 3 3,5 4 years
  23. 23. Severity score (Zimran) SS 20 14,8 15 12,4 10,1 10 9,4 8,9 8,1 8,08 8,1 7,9 5 32 32 32 32 29 27 23 22 17 0 0 0,5 1 1,5 2 2,5 3 3,5 4 years
  24. 24. Cerezyme treatment in assessed Gaucher patients: - clinical improvement since the first year of ERT - 4 female patients ...................... 5 healhty children - no side effects - quality of life improved notably
  25. 25. Imigluceraza (Cerezyme) – - extraordinary chance for Gaucher patients early specific diagnoses early start of enzyme replacement therapy
  26. 26. Gaucher patients Day (2005)
  27. 27. Thanks : - European Cerezyme Access Programme - Genzyme Pharmaceutical Company

×