Thematic

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Huntington's Disease map

Cause and effect graph

Huntington's Disease

Build complete 1-level preview
Center Mutant Huntingtin Protein
Cause Antisense Oligonucleotide
Cause Htt Gene Mutation
Cause Sky 0515
Cause Votoplam
Cause Branaplam

Center node

Mutant Huntingtin Protein

The anchor of this map (entity). Its strongest causes and effects fan out around it.

Causal relationship

Antisense Oligonucleotide → Mutant Huntingtin Protein

ASOs lower mutant huntingtin expression in Huntington mouse models

Opposing (-) 0.44

Causal relationship

Htt Gene Mutation → Mutant Huntingtin Protein

Inherited CAG repeat expansion in HTT gene drives production of toxic mutant huntingtin protein

Reinforcing (+) 0.44

Causal relationship

Sky 0515 → Mutant Huntingtin Protein

dose-dependent knockdown of mutant huntingtin protein observed in Phase 1 clinical update

Opposing (-) 0.43

Causal relationship

Votoplam → Mutant Huntingtin Protein

Votoplam (PTC518) is an oral small-molecule splicing modifier that forces a premature stop into HTT mRNA, degrading the transcript and lowering huntingtin protein; PIVOT-HD showed dose-dependent lowering (23% low / 36% high dose at 1 year)

Opposing (-) 0.36

Causal relationship

Branaplam → Mutant Huntingtin Protein

Oral drug branaplam lowered huntingtin levels in HD patients.

Opposing (-) 0.36

Mutant Huntingtin Protein

Where the map converges: 5 causes feed in.

Evidence

0.44

Inherited CAG repeat expansion in HTT gene drives production of toxic mutant huntingtin protein

Source: strongest evidenced cause link

Node detail

strength 44

Antisense Oligonucleotide

Best path: Antisense Oligonucleotide → Mutant Huntingtin Protein

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Finale

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Lineage fans out from the selected center.

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