Condition or disease |
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Lysosomal Storage Diseases |
Lysosomal storage diseases (LSD) often cause severe disability and have a devastating effect on quality of life. The current standard of care of a majority of LSD is enzyme replacement therapy (ERT). ERT, however, becomes less effective during the advanced stages of a disease. Another therapy is substrate reduction therapy (SRT). For example, SRT therapy for Gaucher disease with small molecules acts on ceramide synthesis pathway by decreasing production of the substrate. But, none of the above therapies are effective for treatment of a neuropathic form of LSD. Neurodegenerative changes in the central nervous system are a major problem in Sanfilippo disease. They cause severe disability and behavioral disturbance. This is the main reason for the absence of therapeutic options for MPS3 (Sanfilippo) patients. The future of neuropathic form of LSD therapy may lie in small molecules acting as agents for enzyme-enhancement therapy (EET). EET is based on the ability of small molecules to fold the misfolded mutant enzyme, activate autophagy-lysosomal pathways or mitochondrial function. This treatment approach has the potential to cross the CNS and carries the potential to treat the neurological symptoms of Sanfilippo disease or other types of LSD.
The purpose of this study will evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will be focused on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated.
Study Type : | Observational |
Estimated Enrollment : | 50 participants |
Observational Model: | Case-Only |
Time Perspective: | Prospective |
Official Title: | Cellular Pharmacodynamics of Small Molecules in Sanfilippo Disease(s) (MPS3) and Other Lysosomal Storage Disorders |
Actual Study Start Date : | July 6, 2018 |
Estimated Primary Completion Date : | July 2020 |
Estimated Study Completion Date : | July 2020 |
Group/Cohort |
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LSD
Subjects diagnosed or suspected to have any of the following lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease, Mucopolysaccharidoses.
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Control
Subjects with no known lysosomal storage disorder
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Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
Subjects with
Exclusion Criteria:
Subjects excluded from the study include those who:
Contact: Margarita M Ivanova, PhD | 7032616220 | mivanova@ldrtc.org | |
Contact: Uyensa Beese | 7032616220 | ubeese@ldrtc.org |
United States, Virginia | |
LDRTC | Recruiting |
Fairfax, Virginia, United States, 22030 | |
Contact: Margarita Ivanova, PhD 703-261-6220 mivanova@ldrtc.org | |
Contact: Ozlem M Goker-Alpan, MD 7032616220 ogokar-alpan@ldrtc.org | |
Principal Investigator: Ozlem Goker-Alpan, MD | |
Principal Investigator: Margarita M Ivanova, PhD | |
Sub-Investigator: Renuka Limgala, PhD |
Principal Investigator: | Margarita M Ivanova, PhD | LDRTC | |
Principal Investigator: | Ozlem Goker-Alpan, MD | LDRTC | |
Principal Investigator: | Renuka Limgala, PhD | LDRTC |
Tracking Information | ||||||||||
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First Submitted Date | January 18, 2019 | |||||||||
First Posted Date | January 22, 2019 | |||||||||
Last Update Posted Date | January 22, 2019 | |||||||||
Actual Study Start Date | July 6, 2018 | |||||||||
Estimated Primary Completion Date | July 2020 (Final data collection date for primary outcome measure) | |||||||||
Current Primary Outcome Measures |
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Original Primary Outcome Measures | Same as current | |||||||||
Change History | No Changes Posted | |||||||||
Current Secondary Outcome Measures | Not Provided | |||||||||
Original Secondary Outcome Measures | Not Provided | |||||||||
Current Other Pre-specified Outcome Measures | Not Provided | |||||||||
Original Other Pre-specified Outcome Measures | Not Provided | |||||||||
Descriptive Information | ||||||||||
Brief Title | Cellular Pharmacodynamics of Small Molecules in Lysosomal Storage Disorders | |||||||||
Official Title | Cellular Pharmacodynamics of Small Molecules in Sanfilippo Disease(s) (MPS3) and Other Lysosomal Storage Disorders | |||||||||
Brief Summary | The purpose of this study is to evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will focus on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated. | |||||||||
Detailed Description |
Lysosomal storage diseases (LSD) often cause severe disability and have a devastating effect on quality of life. The current standard of care of a majority of LSD is enzyme replacement therapy (ERT). ERT, however, becomes less effective during the advanced stages of a disease. Another therapy is substrate reduction therapy (SRT). For example, SRT therapy for Gaucher disease with small molecules acts on ceramide synthesis pathway by decreasing production of the substrate. But, none of the above therapies are effective for treatment of a neuropathic form of LSD. Neurodegenerative changes in the central nervous system are a major problem in Sanfilippo disease. They cause severe disability and behavioral disturbance. This is the main reason for the absence of therapeutic options for MPS3 (Sanfilippo) patients. The future of neuropathic form of LSD therapy may lie in small molecules acting as agents for enzyme-enhancement therapy (EET). EET is based on the ability of small molecules to fold the misfolded mutant enzyme, activate autophagy-lysosomal pathways or mitochondrial function. This treatment approach has the potential to cross the CNS and carries the potential to treat the neurological symptoms of Sanfilippo disease or other types of LSD. The purpose of this study will evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will be focused on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated. |
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Study Type | Observational | |||||||||
Study Design | Observational Model: Case-Only Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | |||||||||
Biospecimen | Not Provided | |||||||||
Sampling Method | Non-Probability Sample | |||||||||
Study Population | Patients diagnosed or suspected of having a lysosomal storage disorder and family members of diagnosed patients will be recruited. Informed consent will be obtained prior to the execution of any research procedures. | |||||||||
Condition | Lysosomal Storage Diseases | |||||||||
Intervention | Not Provided | |||||||||
Study Groups/Cohorts |
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Publications * | Not Provided | |||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||||||||
Recruitment Status | Unknown status | |||||||||
Estimated Enrollment |
50 | |||||||||
Original Estimated Enrollment | Same as current | |||||||||
Estimated Study Completion Date | July 2020 | |||||||||
Estimated Primary Completion Date | July 2020 (Final data collection date for primary outcome measure) | |||||||||
Eligibility Criteria |
Inclusion Criteria: Subjects with
Exclusion Criteria: Subjects excluded from the study include those who:
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Sex/Gender |
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Ages | Child, Adult, Older Adult | |||||||||
Accepts Healthy Volunteers | Yes | |||||||||
Contacts | Contact information is only displayed when the study is recruiting subjects | |||||||||
Listed Location Countries | United States | |||||||||
Removed Location Countries | ||||||||||
Administrative Information | ||||||||||
NCT Number | NCT03812055 | |||||||||
Other Study ID Numbers | 18-LDRTC-02 | |||||||||
Has Data Monitoring Committee | No | |||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Responsible Party | Lysosomal and Rare Disorders Research and Treatment Center, Inc. | |||||||||
Study Sponsor | Lysosomal and Rare Disorders Research and Treatment Center, Inc. | |||||||||
Collaborators | Not Provided | |||||||||
Investigators |
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PRS Account | Lysosomal and Rare Disorders Research and Treatment Center, Inc. | |||||||||
Verification Date | January 2019 |