INT241799

Context Info Confidence 0.42 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 13 Total Number 13 Disease Relevance 4.37 Pain Relevance 0.44

extracellular space (CHIT1) extracellular region (CHIT1) carbohydrate metabolic process (CHIT1) lysosome (CHIT1)

Anatomy Link Frequency platelet 5 leukocyte 1 liver 1 brain 1 spleen 1 CHIT1 (Homo sapiens)

Pain Link Frequency Relevance Heat peripheral neuropathy 25 80.84 abdominal pain 4 77.36 Paresthesia 4 73.12 Pain 49 72.56 imagery 28 57.44 agonist 1 22.20 Central nervous system 16 5.00 Analgesic 7 5.00 Inflammation 6 5.00 tolerance 3 5.00

Disease Link Frequency Relevance Heat Gauchers Disease 402 98.24 Neurologic Manifestations 18 94.56 Weight Loss 32 94.40 Splenomegaly 17 93.84 Diarrhoea 36 93.76 Hepatomegaly 15 92.24 Disease 91 89.92 Adverse Drug Reaction 8 84.96 Peripheral Neuropathy 25 80.84 Tremor 17 79.80

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The level of chitinase decreased in the quebracho group.

Negative_regulation (decreased) of chitinase

1) Confidence 0.42 Published 2010 Journal Proteome Sci Section Body Doc Link PMC3018447 Disease Relevance 0 Pain Relevance 0

Two covariates affected the chitotriosidase decrease under ERT: splenectomy influenced the slope decline and genotype influenced the baseline level (Figure 2b).

Negative_regulation (decrease) of chitotriosidase

2) Confidence 0.24 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.07 Pain Relevance 0

Chitotriosidase levels decreased, without reaching a normal level over a median of six (range, 0 to 15) years of follow-up.

Negative_regulation (decreased) of Chitotriosidase

3) Confidence 0.21 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.10 Pain Relevance 0

For patients given full-dose ERT, platelet counts increased slightly faster, ferritin and TRAP decreased faster, but chitotriosidase and ACE declined more slowly.

Negative_regulation (declined) of chitotriosidase in platelet

4) Confidence 0.15 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.18 Pain Relevance 0

During ERT, clinical abnormality rates decreased (except for neurological involvement) and the biological data improved overall during ERT (increased hemoglobin, leukocyte and platelet levels; decreased chitotriosidase, ACE, TRAP, ferritin and gammaglobulin levels).

Negative_regulation (decreased) of chitotriosidase in platelet

5) Confidence 0.15 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.27 Pain Relevance 0

Platelet counts in nonsplenectomized patients were stable before ERT (+190 platelets/year), while chitotriosidase and TRAP decreased slightly, and ferritin and ACE increased slightly.

Negative_regulation (decreased) of chitotriosidase in Platelet

6) Confidence 0.15 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.32 Pain Relevance 0.09

For some biomarkers, not all patients had the same evolution under ERT: for example, platelet counts rose in 97% of treated patients, while chitotriosidase decreased in 100% and ferritin in 96%, but ACE levels in only 78%.

Negative_regulation (decreased) of chitotriosidase in platelet

7) Confidence 0.15 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.39 Pain Relevance 0

At 6 months, the previously untreated group showed a mean increase in hemoglobin of 0.77 g/dL, platelet count of 41.5 × 109/L or remained stable, and a mean decrease in their chitotriosidase levels of 38.2% (Table 1).

Negative_regulation (decrease) of chitotriosidase in platelet

8) Confidence 0.11 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2504062 Disease Relevance 0.80 Pain Relevance 0.14

Chitotriosidase levels decreased by 25.4% over 2 years (Table 1).

Negative_regulation (decreased) of Chitotriosidase

9) Confidence 0.11 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2504062 Disease Relevance 0.47 Pain Relevance 0.11

After a total of 12 months’ treatment, spleen and liver volumes, and chitotriosidase levels decreased by only 10%, 6%, and 15%, respectively (Table 1).

Negative_regulation (decreased) of chitotriosidase in liver

10) Confidence 0.10 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2504062 Disease Relevance 0.38 Pain Relevance 0.03

Unlike recombinant enzymes, SRT agents are small molecules that can cross the blood-brain barrier.59 Although improved pulmonary function, and a significant decrease in chitotriosidase levels have been observed in patients with GD type 3, miglustat unfortunately, does not appear to have any significant benefits on the neurological manifestations of GD.60

Negative_regulation (decrease) of chitotriosidase in brain associated with gauchers disease and neurologic manifestations

11) Confidence 0.06 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.75 Pain Relevance 0.04

During ERT, clinical abnormality rates decreased (except for neurological involvement) and the biological data improved overall during ERT (increased hemoglobin, leukocyte and platelet levels; decreased chitotriosidase, ACE, TRAP, ferritin and gammaglobulin levels).

Negative_regulation (decreased) of chitotriosidase in leukocyte

12) Confidence 0.05 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945057 Disease Relevance 0.27 Pain Relevance 0

After a total of 12 months’ treatment, spleen and liver volumes, and chitotriosidase levels decreased by only 10%, 6%, and 15%, respectively (Table 1).

Negative_regulation (decreased) of chitotriosidase in spleen

13) Confidence 0.03 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2504062 Disease Relevance 0.38 Pain Relevance 0.03

General Comments

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