Brain Bank
Queen Square Brain Bank for Neurological Disorders (QSBB) = UCL: NETA 찾은
| site | n |
|---|---|
| edinburgh | 51 |
| KCL | 14 (논문엔 많았는데 (우측) DB엔 X.) |
| Newcastle | 4 |
| oxford | 15 |
| Manchester | 1 |
| Bristol | 2 |
| Sheffield | |
| Cambridge | 14 |
NCNP: 분명 MRC BB 이 일부인데 db에는 x.
UCL: A lot of, only ~three matched CSF & plasma, John Hardy and Chelban, Viorica v.chelban@ucl.ac.uk
Roy Alcalay’s recommendation.
Clinical Progression
Onset: 56.2 y (sd 8.4) (Wenning et al., 2013, PMID: 23391524)
The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10) {Watanabe, 2002 #1418}
Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. {Watanabe, 2002 #1418}
- 60% of patients require a wheelchair within 5 y of onset of motor symptoms,
- wheelchair-dependency occur on average after 6.7 years from disease-onset
- survival from onset: 9.8 y
Clinical Trial example
20181001 TAK-341 IDP page14
The aim of this study is to assess a significant reduction in symptom severity with TAK-341 treatment. According to available observational data about disease progression (Wenning et al. 2013), the selected Study Population, i.e., MSA patients is expected to show mean change (SD) of UMSAR scale over 1 year of 14.6 (11.8) points.
Clinical relevant change indicating therapeutic effects of TAK-314 using the UMSARS scale at 12 months was set at 5 (10.4) point difference vs. placebo (Poewe et al. 2015). Assuming 15% misdiagnosed - and hence no effect - the overall ES is 0.41. Using a 3-arm study design (i.e. placebo and 2 dose of TAK-341), alpha with Holm’s step down procedure = 0.10 (two-sided) and Power = 90%, the estimated number of subjects will be about 119/arm, for a total of n=357.
Cohort
| cohort | institution | description | n |
|---|---|---|---|
| Multiple System Atrophy Coalition | https://www.multiplesystematrophy.org/press-releases/the-multiple-system-atrophy-coalition-announces-a-groundbreaking-project-to-explore-the-genetics-of-msa/ ~2,000, include, 김한준, 전범석, | ~2000 | |
| Track-MSA | NYU study | collect clinical, neurological, blood, CSF, and neuroimaging biomarkers with assessments at 6 months and 12 months. (https://clinicaltrials.gov/ct2/show/NCT04450992) They will have UMSARS and NfL but in 2023. However, maybe they could share some preliminary data because it is an observational, non-interventional, longitudinal natural history study. The goal is to define changes in clinical, neurological, blood, CSF, and neuroimaging biomarkers in patients with MSA comparing baseline to 6-month and 1-year assessments. | 50 patients with MSA-P or MSA-C at 2 or more participating sites. |
| HoRC-MSA (Hokkaido Rare Disease Consortium for MSA) | Hokkaido Univ, since 2014. http://neurology.med.hokudai.ac.jp/~neuro-w/horc-msa/greeting/. Department of Neurology, Graduate School of Medicine, Hokkaido University, Ichiro Yabe |
Representative of HoRC-MSA Professor, Masaaki Matsushima No CSF sample, UMSARS part II change (fig 3b, n=16) {Matsushima, 2021 #1389} Final decision will be considered at a meeting of this research group including Professor Yabe sharing their natural history data with us. Dr. Matsushima replied on Sep 3rd, that he personally was positive on sharing their natural history data with us but they would let us know of their group's final decision after internal discussion. I am waiting for their final decision on sharing their data with Takeda. you keep CSF samples (only baseline, more than 40 cases?) I checked the recent total number of patients I told you the other day. The number of patients who went up to the evaluation of UMSARS Part 2 and ICLEMSA was 142 for the first evaluation, 95 for the second evaluation, 47 for the third evaluation, 24 for the fourth evaluation, and 10 for the fifth evaluation. Regarding the MSA blood samples accumulated in our department, there were 50 cases of serum, 140 cases of plasma, and 120 cases of DNA. Js: I captured from the conversation that HoRC-MSA now has more than 100 cases who has second year evaluation of UMSARS and ICLEMSA (and ~20 cases with fifth year evaluation), and more than 20 cases with longitudinal data of DATscan and MRI (T2 and proton density). This is a quick capture from the conversation, so please correct if anything is incorrect | {Matsushima, 2021 #1389} 104 patients performed the second-year evaluation, 71 the third-, 41 the fourth-year evaluation and 17 the fifth-year evaluation. |
Term of the agreement: 2021/7/20 - 2022/1/30
Work hours: up to 5 hours
[Meeting Dr. Matsushima 20210730 mmasaaki@huhp.hokudai.ac.jp]
and copy Saito-san and myself to your email. and copy Saito-san and myself to your email.
MSA-P is severer and more rapid progression than MSA-C, but they can be combined in a protocol.
Mixed type is just a feature appearing in advanced stage.
HORC-MSA cohort
| readout | Longitudinal data |
|---|---|
| DATscan | 20-30 longi |
| MRI (T2, proton density) | |
| UMSARS (ME) | 142 for the first evaluation, 95 for the second evaluation, 47 for the third evaluation, 24 for the fourth evaluation, and 10 for the fifth evaluation. |
| ICLEMSA | |
| VMRI | X |
| CSF | Only one point n=40-50, No analysis done but just keeping the sample |
| Blood | 아래 다 one point 인가? 50 cases of serum, 140 cases of plasma, and 120 cases of DNA |
Next action: email to Jaya (no yabe), confidentiality obligation 5y → outline of Takeda’s proposal → internal discussion on both sides
[Payment]
Implementation Report and the Ariba Input Request Form, the Bank Account Information Form (to receive from Kimiko), Agreement → Murata-san (mariko.murata1@takeda.com) (자료 1부 by post vs email). 541-0045 大阪府大阪市中央区道修町四丁目1番1号 武田薬品工業株式会社御堂筋ビル7F TBSファイナンスソリューションズジャパン → Ariba will send you an email. → When you receive the email, please forward it to me (Yuko Fujimori), along with a request for proxy processing. (I will set an alarm just in case.)
MSAR study (Hospital Clinic de Barcelona, Spain) / BIOMUSE
Vanderbilt University Medical Center in the US under the direction of Daniel Claassen, MD, (PI). Located at Vanderbilt University (PI: David Claassen) and sponsored by Alterity.
“US FDA has encouraged Alterity to utilize data from the bioMUSE study to aid in the development of efficacy endpoints for the Phase 2 study”
{Gilman, 2005 #2189}: clinical scales, repository of biological samples and cell lines.
Design: Observational (no treatment)
- Identify biomarker(s) suitable for endpoint in treatment study
- Evaluate the change in biomarkers and clinical scales in patients with early MSA to track disease progression
- Population: Early MSA patients similar to Phase 2 population
- Observation period: 12 months
- Sample size: 10
- Biomarkers
- MRI: Iron content, regional blood flow/metabolism, neuromelanin, oxidative stress
- Protein: NFL (CSF, plasma), Aggregating a-syn (CSF), phos-a-syn (skin)
- Wearable movement sensors
- Clinical Endpoints
- Clinical: Motor exam, UMSARS (function/ADL inventory), global assessments of severity and change (clinician, patient)
- Functional: Timed Up and Go
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Wenning citation | (Wenning et al. 2013), the selected Study Population | The Wenning citation is referenced but the parenthetical includes a misspelling UMSAR for UMSARS; preserved as visible. |
| HoRC-MSA evaluations counts | 142 for the first evaluation, 95 for the second… | Two different paragraphs in the source give slightly different counts (104 / 71 / 41 / 17 in the {Matsushima, 2021 #1389} citation vs 142 / 95 / 47 / 24 / 10 from Matsushima’s email). Both readings preserved as visible. |
| Cohort size note | ~2,000, include, 김한준, 전범석, | Two Korean PI names appear in the MSA Coalition row; preserved as visible. |
| Address line | 541-0045 大阪府大阪市中央区道修町四丁目1番1号 武田薬品工業株式会社御堂筋ビル7F TBSファイナンスソリューションズジャパン | Japanese address line is partly stylized in the OCR; reading reconstructed from kanji-by-kanji reading. |