MedPath

Mitochondrial Dysfunction and Disease Progression

Completed
Conditions
Secondary Progressive Multiple Sclerosis
Primary Progressive Multiple Sclerosis
Clinically Isolated Syndrome
Relapsing-Remitting Multiple Sclerosis
Registration Number
NCT02549703
Lead Sponsor
Icahn School of Medicine at Mount Sinai
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
47
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Spare respiratory capacity2 years

Mitochondrial bioenergetic measurements

Oxygen consumption rate2 years

Mitochondrial bioenergetic measurements

Secondary Outcome Measures
NameTimeMethod
Expanded Disability Status Scale2 years

a formalized version of the neurological examination

Multiple Sclerosis Functional Composite (MSFC) Score2 years

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.

MS Impact Scale-29 (MSIS-29)2 years

a quality of life measure; an overall measure of functioning from the patient's perspective

Trial Locations

Locations (1)

Icahn School of Medicine

🇺🇸

New York, New York, United States

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