karafecho
commented
3 years ago Note that this use case does not work for Exposures Provider, but may work for Clinical Data Provider and Multi-omics EHR Risk Provider, and sort of works for Connections Hypotheses Provider. The challenge for Clinical Data Provider and Multi-omics EHR Risk Provider is that these are rare cases, so the sample sizes may represent an issue due to regulatory and computational constraints.
Candidate No. 4: mediKanren Real-world Use Cases [NCATS, Unsecret Agent]
(Also see this doc)
Acanthosis nigricans: Patient presented with acanthosis nigricans. Genomic sequencing revealed variants in multiple genes. Causal variant was a gain of function in EGFR. MediKanren recommended erlotinib. We compounded it as a topical cream with a specialist pharmacy, and the patient applied to one arm, but not the other. Significant reduction in the skin growths occurred on the treated arm.
Severe ataxic episodes: Patient presented with ataxic episodes. Genomic sequencing revealed multiple variants. Causal variant was a missense mutation in the domain controlling degradation of RHOBTB2, hence making it a gain of function in RHOBTB2. No direct RHOBTB2 inhibitors are known to exist, but several indirector downregulators of RHOBTB2 (via E2F1) do exist, and celecoxib showed a substantial reduction in ataxic episodes.
Extreme developmental delay; non-ambulatory at age 5: Patient presented with multiple VUSes. Causal variant was determined to be in MAPK8IP3, leading to predicted haploinsufficiency. Retinoic acid is a potent upregulator of MAPK8IP3. 6 months of treatment with vitamin A lead to patient standing and taking simple steps. 18 months of treatments led to patient walking freely under own power and notable cognitive gains.