Therapeutic developments for valosin-containing protein mediated multisystem proteinopathy
Bibliographic record
Abstract
PURPOSE OF REVIEW: Missense mutations in valosin-containing protein (VCP) can lead to a multisystem proteinopathy 1 (MSP1) with any combination of limb-girdle distribution inclusion body myopathy (IBM) (present in about 90% of cases), Paget's disease of bone, and frontotemporal dementia (IBMPFD). VCP mutations lead to gain of function activity with widespread disarray in cellular function, with enhanced ATPase activity, increased binding with its cofactors, and reduced mitofusin levels. RECENT FINDINGS: This review highlights novel therapeutic approaches in VCP-MSP in in-vitro and in-vivo models. Furthermore, we also discuss therapies targeting mitochondrial dysfunction, autophagy, TDP-43 pathways, and gene therapies in other diseases with similar pathway involvement which can also be applicable in VCP-MSP. SUMMARY: Being a rare disease, it is challenging to perform large-scale randomized control trials (RCTs) in VCP-MSP. However, it is important to recognize potential therapeutic targets, and assess their safety and efficacy in preclinical models, to initiate RCTs for potential therapies in this debilitating disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".