Repurposing off-patent compounds for CMT1A.
SharkTooth Bio is using Urchin to identify off-patent compounds for Charcot-Marie-Tooth Disease Type 1A, a disease with no approved treatments.
There isn't much literature on CMT1A, so being able to bring in experimental data to seed the search was critical. Urchin's analysis led us to include a class of drugs for in vivo testing that we hadn't originally considered.
David Apple, Founder and CEO, SharkTooth Bio
1.6MPeopleLiving with CMT1A worldwide, with no approved treatments.
19CompoundsSelected for in vivo testing, with dosing informed by Urchin.
6Output categoriesEach one fed a decision on the program.
1Drug classSurfaced by Urchin, not originally prioritized.
Source: engagement recordSharkTooth Bio
Project overview
Context
CMT1A is an inherited peripheral neuropathy affecting approximately 1.6 million people worldwide. There are currently no approved treatments for it. SharkTooth Bio's mission is to create them, and they sought a fast, capital-efficient path through drug repurposing, pursuing off-patent compounds while simultaneously investing in longer-term, new modalities.
The challenge
Rare disease therapeutic development is constrained by sparse literature, fragmented evidence, and limited mechanistic understanding. Conventional AI tools trained on well-characterized disease biology offer limited utility in this setting: there is no dense center of the distribution to search.
What Urchin did
Urchin integrated SharkTooth's proprietary time-series RNA-sequencing data from CMT1A mouse models with a broad array of public evidence: literature, pathway and functional annotations, genetics and disease databases, pharmacology and compound datasets, and high-throughput screening data. Six categories of output came back, and each one fed a decision.
- Pathway-level mechanistic analyses: reconstructing disease-relevant pathways and perturbed biology.
- Prioritized therapeutic hypotheses: identifying biologically actionable intervention points and mechanisms.
- Compound nomination and rationale: nominating compounds and drug classes with mechanistic justifications.
- Analogue exploration: exploring structural analogues to identify compounds with potentially improved safety or pharmacologic profiles.
- Transcriptomic integration: using RNA-seq evidence to refine mechanisms and prioritize interventions.
- In vivo design support: informing dosing strategies and experimental design considerations.
Impact
Urchin's analysis surfaced a drug class that SharkTooth's scientific advisors had not originally prioritized, expanded the set of experimentally testable hypotheses, and directly informed the selection and dosing of 19 compounds now undergoing in vivo testing.