hanna rosenbaum , md hematology and bone marrow...
TRANSCRIPT
![Page 1: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/1.jpg)
POTENTIAL LINK BETWEEN GAUCHER DISEASE PATHWAYS
AND THOSE OF PARKINSON DISEASE
Hanna Rosenbaum , MD
Hematology and Bone Marrow TransplantationRambam Medical Center and
Bruce Rappaport Faculty of Medicine Haifa, Israel
![Page 2: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/2.jpg)
Phillip Gaucher James Parkinson 1882 1817
![Page 3: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/3.jpg)
![Page 4: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/4.jpg)
C C CH2 O
C O
H H
OH
OH
N
CH2OH
OH
OH
OH
O
Glucocerebroside + H20 Ceramide + GlucoseGlucocerebrosidase
Macrophage Gaucher MacrophageSidransky and LaMarca, 2003
![Page 5: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/5.jpg)
Gaucher Disease Subtypes
Non-neuronopathic, Type 1
�Prevalent in Ashkenazi Jews.
�Onset at any age
Neuronopathic, Types 2 and 3
�Type 2 (acute)
� Pan ethnic
� Onset in infancy
� Life expectancy 2 to 3 years
�Type 3 (chronic)
� Pan ethnic
� Onset in infancy/childhood
![Page 6: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/6.jpg)
Type 1
Type 2
Type 3Sidransky and LaMarca, 2003
Gaucher Disease Phenotypes
![Page 7: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/7.jpg)
Sidransky and LaMarca, 2003
Mutations in Glucocerebrosidase
84GG1023C DEL
1VS2+1
R120Q
A176N
G202R P182T
L444PΨΨΨΨ
K157Q
P122S
N188SΨΨΨΨF213 I ΨΨΨΨ
D140H
R463C
Y212H
D399NV394LD409HΨΨΨΨP415R
N370S
55 bp del ΨΨΨΨ
W378G
D380N
D380A
F417V
A309V
G478S
T3231
G325RΨΨΨΨ
W312CS364TC342GE326K
Y313HR359Q
D409V
R496HR463C R463Q
L425E
Complex Allele B (Rec TL)ΨΨΨΨD409H, L444P, A456P, V460VComplex Allele A (Rec Nci)ΨΨΨΨ
L444P, A456P, V460V
1
2
3
4
5
6
7
8
9
10
11
R285CR257QF216YP289L
![Page 8: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/8.jpg)
Type 1 Gaucher Disease: Affected Organs and Manifestations
Macrophages
Bone Marrow
Beutler and Grabowski, The Metabolic and Molecular Bases of Inherited Disease 2001
Skeletal pathology
Pulmonary hypertension
Hepatomegaly Splenomegaly
![Page 9: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/9.jpg)
HEMATOLOGICAL MANIFESTATIONS
Splenomegaly
Pancytopenia : anemia,thrombocytopenia
Leucopenia, impaired neutrophil function
Bleeding tendency
Marrow infiltration and fibrosis
Monoclonal gammopathies
Autoimmune phenomena
![Page 10: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/10.jpg)
Skeletal Involvement
![Page 11: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/11.jpg)
Parkinson disease
� Prevalence: 1/100
� Main symptoms:
Resting tremor, Akinesia, Rigidity Postural instability
Neurobehavioral changes
� Pathophysiology:
Degeneration of dopaminergic neurons SN pars compacta
![Page 12: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/12.jpg)
Etiology
Familial cases are rare
Most cases are sporadic
Genetic factors PARK genes
Park1-Synuclein on 4q
Park 2-parkin on 6q
ubiquitin hydrolase - L1 on 4p14
Park 7-DJ-1 1p36
Environmental factors
![Page 13: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/13.jpg)
Patient No.
� A 50 year old Ashkenazi female.
� Type 1 Gaucher homozygous N370S diagnosed at age 9.
� Splenectomy at age 13.
� Hepatomegaly, no bone involvement.
� Obsessive-compulsive disorder at age 38.
� 4 years later kyphotic posture and gait disturbance.
� Bilateral Parkinsonian features since age 48 including : cogwheel rigidity, bradykinesia,
![Page 14: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/14.jpg)
Cognitive examination
� Dysexecutative syndrome : impaired attention and concentration, perseverations
� Impaired memory and confabulations.
� Visual-spatial impairment and visual hallucinations.
� At age 50 developed dementia and became bedridden.
� Died at age 52.
� Dx: Parkinson disease, Lewy body dementia.
![Page 15: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/15.jpg)
Background
Among 90 Ashkenazi Jewish Type 1 Gaucher patients followed at the Rambam medical center in Haifa, Israel 3(3.3%) presented Parkinsonian manifestations.
One of the patients was the first documented N370S/N370S genotype with Parkinsonism (Varkonyi et al,2002).
![Page 16: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/16.jpg)
Goals
Evaluate:
�Prevalence of common Gaucher mutations among
Ashkenazi Jewish patients with Parkinson disease.
�Relevance of glucocerebrosidase mutations to the severity
and progression of Parkinsonian symptoms.
� Incidence of Parkinson disease among relatives of
Gaucher Patients
![Page 17: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/17.jpg)
Methods (1)
Patients population
� 157 consecutive Ashkenazi Jewish patients
with idiopathic Parkinson disease.
Control population
� 74 patients with Alzheimer disease.
� 1543 healthy Ashkenazi individuals
![Page 18: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/18.jpg)
Results (1)
N370S other carriers (%) 95% CI
Parkinson
n=157
31 *het
5 ♦ homo
4 het (84GG)
3 het (R496H)
43(27.4 %) 19.6-34.4%
Alzheimer
n=74
2 het 1 het (84GG) 3 (4.1% ) 0.0-8.5
Controls
n=1543
92 het 3 het (84GG) 95 (6.2%)
♦homozygote
*heterozygote
5-7.4
![Page 19: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/19.jpg)
Results (2)
Frequency of mutant allele
�Parkinson patients N370S 1:3.65
84GG 1:39.75
�Control population N370S 1:16.7
84GG 1:514
![Page 20: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/20.jpg)
Results (3)
Number of Gaucher disease carriers among Parkinson patients exceeds that observed among normal controls
OR = 5.7 CI 3.7-8.8 p<0.0001
Number of Gaucher disease carriers amongParkinson disease patients exceeds that observed among Alzheimer patients
OR =8.9 CI 2.5-25.2 p=0.0008
![Page 21: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/21.jpg)
November 2004
![Page 22: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/22.jpg)
Clinical characteristics of Type I GD and PD
Pt Sex Age GD
PD fam. history
Age of
PD onset
GD PD
1 F 28 50 Splenectomy
(30) AVN, HIP
Limited response to
L-DOPA, psychosis
died at 61
2 F 30 47 Bleeding bone crisis organomegaly
Progression on
L-DAPA died at 58
3 F 9 Aunt 48 Splenectomy (13) Progression dementia, psychosis
4 F 59 2 uncles 43 Organomegaly ocular manifestation
Responsive to L-DOPA excellent response to DBS*
5 F 58 Mother 58 Pulmonary, hypertension, osteopenia
Responsive to L-DOPA
6 M 18 49 Splenomegaly, bone infarcts, osteopenia
Lt Hem PD.
![Page 23: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/23.jpg)
PD in family members of Ashkenazi GD patients
12/43 (28%) GD patients have relatives with PDAdditionalGDPD onsetPD family historyGenotypeSexAge
severe50-55mother+2 gf84GG/1604f18
Dementiasevere50grandfather84GG/1226m20
Retinal GD?mild552 uncles1226/1226f59
PHTsevere46sister1226/1226m31
mild65grandmother1226/1226m18
mildmother1226/1226f27
mild70father + aunt1226/1226m18
Nephrotic syndromemild55, 672 aunts ident twins1226/1226f32
65aunt1226/1226m40
mild40mother1226/1226f61
mild70grandmother1226/1226m8
Dementiasevere60,64mother + aunt1226/1226f13
![Page 24: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/24.jpg)
Incidence of PD among Relatives of GD
Patients
Goker-Alpan, NIH 2004 9/40 families (22%)
Halperin, Jerusalem 2006 (27.3%)
![Page 25: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/25.jpg)
Pedigree of Gaucher patient with family
history of Parkinson (1)
5555
50 52
/1604 84GG/
GD GD
84GG/1604 84GG/1604 84GG/1604
GD
28 24 18
![Page 26: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/26.jpg)
Pedigree of Gaucher patient with family
history of Parkinson (2)
GD
1226/ 1226
55 67
Identical twins
![Page 27: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/27.jpg)
In summary (1)
Gaucher mutations among Parkinson patients
� A high frequency of the mutant N370Sglucocerebrosidase allele was detected among Parkinson patients - increased by 5 - fold of healthy Ashkenazi controls.
� The frequency of 84GG allele was 13 times of the control group (p<0.001).
![Page 28: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/28.jpg)
(2)Frequency of PD among relatives of Gaucher
patients
� A high rate of Parkinson disease was found among
relatives of Gaucher patients (confirmed and obligate
carriers of Glucocerebrosidase mutations).
![Page 29: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/29.jpg)
(3)Clinical, pathologic, and genetic studies
suggest:
� Glucocerebrosidase deficiency may predispose
subjects to the development of Parkinson disease.
![Page 30: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/30.jpg)
The odds ratio for any GBA mutation in PD patients versus controls was 5.43 NEJM 2009
![Page 31: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/31.jpg)
The link between Gaucher Disease and Parkinson
Gaucher cells Lewy body
![Page 32: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/32.jpg)
� Glucocerebrosidase mutations are the most common geneticrisk factor for Parkinson disease and Lewy bodies dementia.
� Neurodegeneration in Parkinson disease is accompanied by formation of Lewy bodies and Lewy neurites
� Lewy bodies contain aggregates of the presynaptic protein α-Synuclein.
� In patients with GBA mutations Glucocerebrosidase was present in most Lewy bodies.
� α- Synuclein tends to aggregate into toxic oligomers which areassociated with cell death and neurodegeneration.
LEWY BODIES AND THE ROLE OF Α-SYNUCLEIN
![Page 33: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/33.jpg)
Model of interactions among proteins
in Parkinsons disease
Feany MB NEJM 351:1937 2004
![Page 34: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/34.jpg)
Potential mechanisms linking mutant GCase with PD. Loss of enzymatic function owing to mutation might result in a pathogenic positive-feedback loop, as proposed by Mazzulli et al.
Kinghorn K J Dis. Model. Mech. 2011
![Page 35: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/35.jpg)
Putative models for α- Synuclein turn over pathways affected in Gaucher disease
Westbroek W et al, Trend in Molecular Medicine, 2011
![Page 36: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/36.jpg)
Impaired ERAD-mediated breakdown of GCase
Westbroek W et al, Trend in Molecular Medicine, 2011
![Page 37: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/37.jpg)
A theoretical model for α-Synuclein as a prion in GBA-associated parkinsonism
Westbroek W et al, Trend in Molecular Medicine, 2011 – Adapted from Goldin E Mol Genet Metab 2010
![Page 38: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/38.jpg)
A timeline of the generation of mouse models of GD.
Farfel-Becker T et al. Dis. Model. Mech. 2011
![Page 39: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/39.jpg)
In vivo α-syn-GCase interaction.
Yap T L et al. J. Biol. Chem. 2011
![Page 40: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/40.jpg)
IN CONCLUSION
�Only a small percentage of Gaucher patients and carriers develop Parkinson Disease.
�The role of reduced enzyme activity and substrate accumulation on the α-Synuclein pathology is yet not clear.
�Animal and cell models should be developed for the research of concomitant Gaucher disease and Parkinson.
�The challenge in the future should include recognition of risk factors and development of therapeutic agents for coexistence of Gaucher disease and Parkinson.
![Page 41: Hanna Rosenbaum , MD Hematology and Bone Marrow ...download2.eurordis.org/ecrd2012/T4S0401_H_ROSENBAUM.pdf · Clinical characteristics of Type I GD and PD Pt Sex Age GD PD fam. history](https://reader033.vdocuments.us/reader033/viewer/2022042317/5f066d897e708231d417f1a0/html5/thumbnails/41.jpg)
Whoever saves one life
saves the entire world
SANHEDRIN