Mitochondrial Dysfunction and Disease Progression
While the last several years have seen great strides in the treatment of relapsing forms of MS, progressive MS, responsible for the majority of MS-related disability, lags far behind. Despite much research, the lack of understanding related to what causes patients' relentless decline in function results in an inability to develop targeted treatment strategies suitable for clinical trials. This grant has two main goals.
The first goal is to extend the investigators preliminary study on rat neurons treated with the CSF of MS patients to a larger number of Progressive patients in order to validate the initial findings and extend the study to include analysis of human neurons. The initiating PI (Dr. Casaccia) and the Partnering PI and Clinical Neurologist (Dr. Katz Sand) have recently identified components that are present in the CSF of progressive patients that impair the ability of rat neurons to produce energy. The partnering PI, Dr. Quinzii (Columbia University) together with collaborator Dr. Fossati (NY Stem Cells Foundation), have characterized human neurons generated from stem cells derived from skin biopsies of progressive patients and detected the presence of energetic deficits. The experimental plan will build on these results and test hypotheses of disease progression. The overall goal is to improve understanding on how to stop neurons from degenerating and stop clinical progression.
The second goal is to ask whether it is possible to define a progressive disease course on the basis of combined biochemical, functional and imaging measurements. The initiating PI will be responsible for the biochemical assessment of CSF and serum samples and, together with partnering PI Quinzii, will also provide functional bioassays measurements of mitochondrial bioenergetics impairment in patients. These data will be combined with clinical assessment and MRI evaluations conducted by the partnering PI Katz Sand and collaborator Inglese. A two year clinical and imaging follow up from the initial recruitment will allow to define whether the combined measurements can be used by clinical neurologists to define the disease course and better identify therapeutic options for patients.
The expectation is that the completion of the stated aims of research will allow an advancement of the current knowledge of the progressive form of MS and lead to potential new therapeutic targets.
Visão geral do estudo
Status
Tipo de estudo
Inscrição (Real)
Contactos e Locais
Locais de estudo
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New York
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New York, New York, Estados Unidos, 10029
- Icahn School of Medicine
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
Descrição
Inclusion criteria:
- male and female subjects age 18 or older
diagnosis of one of the following:
- RRMS according to McDonald 2010 criteria or a diagnosis of CIS with clinical symptoms and MRI consistent with MS
- PPMS according to McDonald 2010 criteria
- SPMS defined as at least six months of progressive decline following an initial relapsing disease course
- able and willing to undergo clinical evaluation, MRI, lumbar puncture, and skin biopsy and to return for follow up assessments at the end of year 1 and year 2
- able and willing to provide informed consent.
Exclusion criteria:
- pregnancy
- inability to undergo lumbar puncture, due to anticoagulant therapy that cannot be held for the day of the procedure or results of screening laboratory testing or the presence of another medical condition that would render the procedure unsafe, as determined by the investigator
- inability to undergo MRI, due to the presence of metallic implants incompatible with MRI or any other reason
- presence of other severe medical conditions likely to influence study results or that raise the likelihood of harm to the patient as a result of study participation, as determined by the investigator (e.g. the presence of a brain mass, which could influence the CSF results and also might make lumbar puncture unsafe)
- inability to complete the protocol for any reason
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
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Relapsing Remitting Multiple Sclerosis
Patients with Relapsing Remitting Multiple Sclerosis/Clinically Isolated Syndrome
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Secondary Progressive Multiple Sclerosis
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Primary Progressive Multiple Sclerosis
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Spare respiratory capacity
Prazo: 2 years
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Mitochondrial bioenergetic measurements
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2 years
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Oxygen consumption rate
Prazo: 2 years
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Mitochondrial bioenergetic measurements
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2 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Multiple Sclerosis Functional Composite (MSFC) Score
Prazo: 1 year
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MS disease progression as measured by MSFC score which consists of the Timed 25-foot walk (T25FW) as a measure of ambulation, the Nine-hole peg test (9HPT) as a measure of arm and hand function.
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1 year
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Multiple Sclerosis Functional Composite (MSFC) Score
Prazo: 2 years
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MS disease progression as measured by MSFC score which consists of the Timed 25-foot walk (T25FW) as a measure of ambulation, the Nine-hole peg test (9HPT) as a measure of arm and hand function.
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2 years
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Expanded Disability Status Scale
Prazo: 2 years
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a formalized version of the neurological examination
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2 years
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MS Impact Scale-29 (MSIS-29)
Prazo: 2 years
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a quality of life measure; an overall measure of functioning from the patient's perspective
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2 years
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Ilana Katz Sand, MD, Icahn School of Medicine at Mount Sinai
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Processos Patológicos
- Doenças do Sistema Nervoso
- Doenças do sistema imunológico
- Doenças Autoimunes Desmielinizantes, SNC
- Doenças Autoimunes do Sistema Nervoso
- Doenças Desmielinizantes
- Doenças autoimunes
- Atributos da doença
- Esclerose múltipla
- Esclerose Múltipla Progressiva Crônica
- Esclerose
- Progressão da doença
- Esclerose Múltipla Recorrente-Remitente
Outros números de identificação do estudo
- GCO 14-1495
- CDMRP-MS140072 (Número de outro subsídio/financiamento: US Department of Defense)
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