Gaucher Disease:
Overview and Therapeutic Goals
Gaucher Disease: Overview
 The most common lysosomal storage disease1
 Incidence: approximately 1 in 40,000 for non-Jewish populations3
 Caused by a deficiency of the enzyme glucocerebrosidase1,2
 The glycolipid glucocerebroside accumulates in lysosomes of macrophages1,2
 Lipid-filled Gaucher cells displace normal cells in3





Bone marrow
Spleen
Liver
Lungs
CNS*
CNS = central nervous system.
* In neuronopathic subtypes only.
© 2009 Rector and Visitors of the University
of Virginia. Charles E. Hess, MD, and
Lindsey Krstic, BA, RN (arrow indicates
Gaucher cell)
1. Grabowski GA. Lancet. 2008;372:1263–1271. 2. Futerman AH, et al. Nat Rev Mol Cell Biol. 2004;5:554–565. 3. Sidransky E, et al.
Emedicine Web site. http://www.emedicine.medscape.com/article/944157-overview. Accessed February 12, 2010.
Assessment of Disease Severity
and Development of Treatment
Goals in Type 1 Gaucher Disease
Gaucher Disease: Clinical Signs and
Symptoms
Pulmonary
involvement
Hepatosplenomegaly
Progressive
neurologic
symptoms*
Thrombocytopenia
and anemia
Skeletal
involvement
* In neuronopathic subtypes only.
Grabowski GA. Lancet. 2008;372:1263–1271.
Domain
Assessment
Disease Severity Score Index
1
0
Assessing Disease Severity
Skeletal Domain
Hematological Domain
Biomarker Domain
Visceral Domain
Lung Domain
Neurological Domain
Total
2
3
BMI
absent/minimal
mild
intermediate
severe
Mineral component
absent/minimal
mild
intermediate
severe
Osteonecrosis
none
medullary infarction
osteonecrosis
prosthesis
Fracture
absent
Hemoglobin
> 12 g/dL (male)
> 11.5 g/dL (female)
10–12 g/dL
8–9.9 g/dL
< 8 g/dL*
(*) or need for blood
transfusion
WBC count
> 4 x 109/L
2.5–4 x 109/L
< 2.5 x 109/L
< 1.9 x 109/L
Platelet count
> 150 x 109/L
101–150 x 109/L
60–100 x 109/L
< 60 x 109/L
Bleeding time
< 8 min
> 8 min
Chitotriosidase
< 600 nmol/mL x h
600–4,000
nmol/mL x h
4,001–15,000 nmol/mL x h
> 15,000 nmol/mL x h
CCL 18
< 72 ng/mL
72–236 ng/mL
237–1,000 ng/mL
> 1,000 ng/mL
Spleen
no MR/US lesions
no splenectomy
volume < 5 N
volume
between 5–9 N
splenectomy volume
between 10–15 N
MR/US lesions
volume > 15 N
Liver
no hepatic disease volume
< 1.25 N
volume between
1.25–2.5 N
volume > 2.5 N
hepatic disease
Pulmonary hypertension
absent
moderate
severe
Respiratory failure
absent
moderate
severe
no signs/symptoms
peripheral
neuropathy
+
Parkinson’s
disease/Parkinsonism
Therapeutic Goals
 Developed by a group of physicians from around the world with clinical expertise in
treating Gaucher patients (ICGG)
 Areas targeted for treatment goal development
 Visceral organs
 Liver volume
 Spleen volume
 Hematological
 Anemia
 Thrombocytopenia
 Pulmonary
 Interstitial lung disease
 Pulmonary vascular disease
 Skeletal pathology
 Bone pain/bone crises
 Osteonecrosis and subchondral joint collapse
 Bone mineral density
 Growth (pediatric population)
 Growth patterns/puberty
 Functional health and well-being
 Normal daily activities
 Time frames that are described are based on past experience with
alglucerase/imiglucerase
 These goals may be useful as benchmarks when evaluating treatment regimens
Pastores GM, et al. Semin Hematol. 2004;41(4Suppl 5):4–14.
Therapeutic Goals: Hepatosplenomegaly
Hepatomegaly*
Patients
Goal
Time Frame
All patients
 Reduce liver volume to 1–1.5 times
normal and maintain
All patients
 Reduce liver volume by 20–30%
Years 1 to 2
 Reduce liver volume by 30–40%
Years 3 to 5
Splenomegaly*
Patients
Goal
All patients
 Reduce spleen volume to ≤ 2 to 8 times
normal and maintain
All patients
 Reduce spleen volume by 30–50%
Year 1
 Reduce spleen volume by 50–60%
Years 2 to 5
All patients
Time Frame
 Alleviate symptoms due to
splenomegaly: abdominal distension,
early satiety, new splenic infarction
 Eliminate hypersplenism
*Please note regular assessments will be conducted.
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
Therapeutic Goals: Anemia*
Patients
Goal
Time Frame
Adult female
patients and
children
Hb ≥ 11.0 g/dL
Years 1 to 2
Male patients
> 12 years
Hb ≥ 12.0 g/dL
Years 1 to 2
All patients
 Eliminate blood
transfusion
 Reduce fatigue
 Maintain improved Hb
levels
*Please note regular assessments will be conducted.
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
Therapeutic Goals: Thrombocytopenia*
Patients
Goal
Time Frame
All patients

Sufficient platelets to reduce bleeding
Year 1
Splenectomized patients

Normalization of platelet counts
Year 1

Low-normal platelet counts
Year 2

Continued increases but no normalization
Year 2
Intact spleen
Moderate thrombocytopenia
(> 60,000–< 120,000/mm3)
Severe thrombocytopenia
(< 60,000/mm3)
*Please note regular assessments will be conducted.
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
Therapeutic Goals: Pulmonary Involvement*
Patients
Goal
Patients with overt,
symptomatic
pulmonary
involvement**
 Reverse hepatopulmonary syndrome and
dependency on oxygen
 Ameliorate pulmonary hypertension
 Improve functional status and quality of life
 Prevent rapid deterioration of pulmonary
disease and sudden death
All patients
 Prevent pulmonary disease by timely
initiation of treatment and avoidance of
splenectomy
*Please note regular assessments will be conducted.
** Most patients in this group have had spleen removed.
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
Therapeutic Goals: Bone Disease*
Patients
Goal
Time Frame
All patients
 Lessen or eliminate bone
pain
 Prevent bone crises
 Prevent osteonecrosis and
subchondral joint collapse
1 to 2 years
Pediatric patients
 Improve BMD
2 years
 Attain normal or ideal peak
skeletal mass
 Increase cortical and
trabecular BMD
Adult patients
 Improve BMD
 Increase trabecular BMD
*Please note regular assessments will be conducted.
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
3–5 years
Therapeutic Goals: Pediatric Growth and
Functional Health and Well-being*
Pediatric Growth
Patients
Goal
Time Frame
Pediatric patients
 Normalize growth such that patient
achieves a normal height according to
population standards
Within 3 years
Pediatric patients
 Achieve normal onset of puberty
Functional Health and Well-being
Patients
Goal
All patients
 Improve or restore physical function for
carrying out normal daily activities and
fulfilling functional roles
All patients
 Improve scores from baseline of a
validated quality-of-life instrument
*Please note regular assessments will be conducted.
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
Time Frame
2–3 years or less
(depending on
disease burden)
A Comprehensive Management Plan
 Defined specific management goals
 Act as a guide for managing physicians, consulting specialists, allied health personnel
 Educate patients and families
 Establish reasonable expectations
 Most patients will have multiple therapeutic goals
 To be completed within an expected timeframe
 Maintained for life
 Success depends on
 Comprehensive initial assessment of all potentially affected organs and systems
 Regular monitoring
Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.
Recommendations for Monitoring:
Achieved vs Not Achieved Therapeutic Goals
 Patients on Therapy: For those who are receiving therapy, the frequency of
recommended evaluations is dependent on whether or not a particular patient has
achieved his or her therapeutic goals
 Not Achieved Therapeutic Goals: Until the therapeutic goals have been met, it is advisable to have hemoglobin
levels, platelet counts, and biochemical markers checked at least every 3 months. A thorough physical
examination, as well as visceral and skeletal evaluations, should be completed annually
 Achieved Therapeutic Goals: Once a clear and sustainable response to treatment has been established, the
recommended frequency for checking lab values, visceral response, and skeletal disease diminishes, allowing for
routine monitoring every 12–24 months (at a minimum). However, a thorough physical examination should be
conducted annually
Weinreb NJ, et al. Semin Hematol. 2004;41(suppl 5):15–22.
The Therapeutic Goals MAP Tool
 Designed as a point-of-care management tool by an international taskforce
 Provides a visual representation of patient status and therapeutic outcomes over time
 The MAP tool can be adapted for different patient populations
 For pediatric patients, growth will be displayed as an additional domain
 For splenectomized patients, the splenomegaly domain is omitted
 A biomarker domain can also be incorporated for chitotriosidase (CHITO) and
chemokine (C-C motif) ligand 18 (CCL18)
 Hard copy and electronic versions have been developed
http://www.therapeuticgoalsmap.com/
Therapeutic Goals MAP Tool (electronic) –
Adult and Pediatric Version
Adult
©Shire
Pharmaceuticals Group, 2010.
Pediatric
Therapeutic Goals MAP
Expanding Adoption of Therapeutic Goals
May Assist With Benefit Patient Care
Novel, user-friendly, visual
point-of-care assessment
Many patients do not currently
achieve all the guideline
therapeutic goals1
Encourage and facilitate use of therapeutic goals in day-to-day clinical practice
Standardize a goal-oriented approach, in tandem with regular monitoring,
to optimize patient care
Help in the building of partnerships between physicians and patients
1. Weinreb NJ, et al. Am J Hematol. 2008;83:890–895.
Therapeutic Goals MAP Tool – Summary
 Allows physicians to collate clinical data over time and help guide management by
tracking patient progress using therapeutic goal domains
 Allows other specialists and allied healthcare professionals to closely follow
patients’ progress
 Importantly, by further engaging patients and families in the management process
and enhancing their understanding of clinical outcomes, use of the MAP tool may
create create a partnership in caring
 For more information, please visit www.therapeuticgoalsmap.com or also contact a
Shire Global Medical Affairs representative