Mitochondrial Dysfunction and Disease Progression
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/22/2019 |
| Start Date: | September 2015 |
| End Date: | September 27, 2018 |
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.
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.
Inclusion criteria:
- male and female subjects age 18 or older
- diagnosis of one of the following:
1. RRMS according to McDonald 2010 criteria or a diagnosis of CIS with clinical
symptoms and MRI consistent with MS
2. PPMS according to McDonald 2010 criteria
3. 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
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