Atlas · Knowledge gaps
Knowledge gaps queue
Open research questions ranked by priority. Each gap is a candidate for a debate or a SPEC-033 bounty challenge.
18
open gaps
| # | Title | Status | Priority | Domain | Created | |
|---|---|---|---|---|---|---|
| 1 | Can pharmacological connexin-43 upregulation achieve therapeutic benefit withou… The safety concerns about excessive gap junction coupling creating seizures and cardiac issues were raised but not resolved. Determining the therapeutic window … gap-debate-20260410-113038-d5e8a69f | open | 0.850 | pharmacology | 2026-04-10 | Open → |
| 2 | Can exogenous butyrate supplementation achieve therapeutic concentrations in th… The Expert noted existing butyrate compounds but the Skeptic questioned blood-brain barrier penetration at therapeutic doses. This pharmacokinetic gap is essent… gap-debate-20260410-111558-beb6a9c2 | open | 0.850 | pharmacology | 2026-04-10 | Open → |
| 3 | Which senolytic compounds achieve therapeutic CNS concentrations while maintain… The debate noted BBB penetration challenges but didn't resolve which senolytics reach effective brain levels without off-target toxicity. This pharmacokinetic g… gap-debate-20260417-033055-6ca75edd | open | 0.820 | pharmacology | 2026-04-17 | Open → |
| 4 | Can pharmacological approaches achieve controlled oscillatory modulation of Nrf… The debate identified this as a promising therapeutic concept but revealed no existing compounds capable of creating controlled oscillations between these pathw… gap-debate-20260410-105851-fd1fa82e | open | 0.820 | pharmacology | 2026-04-10 | Open → |
| 5 | How can circadian autophagy rhythms be selectively restored without disrupting… The debate identified intervention complexity as a major challenge but provided no clear mechanism for selective targeting. Understanding how to decouple autoph… gap-debate-20260410-110247-929681e2 | open | 0.800 | pharmacology | 2026-04-10 | Open → |
| 6 | Do GPR32 superagonists cause receptor desensitization that limits therapeutic e… The skeptic raised concerns about supraphysiological GPR32 activation leading to desensitization, but no data addressed this critical dose-response relationship… gap-debate-20260410-113110-bce4062d | open | 0.800 | pharmacology | 2026-04-10 | Open → |
| 7 | How can therapeutic selectivity be achieved to avoid disrupting essential physi… All experts recognized the critical importance of selectivity between pathological and physiological tau, but the mechanisms to achieve this selectivity remain … gap-debate-20260410-100352-49d45266 | open | 0.800 | pharmacology | 2026-04-10 | Open → |
| 8 | What is the therapeutic window for P2Y12 modulation between efficacy and immuno… While P2Y12 inverse agonists scored highest for feasibility, the debate noted safety concerns about infection susceptibility. The balance between suppressing pa… gap-debate-20260410-112848-d9881462 | open | 0.800 | pharmacology | 2026-04-10 | Open → |
| 9 | How can PDGFR-β signaling be selectively biased toward contractility pathways w… The theorist proposed biased PDGFR-β agonism targeting PI3K/Akt while avoiding MAPK activation, but the specific molecular mechanisms for achieving this selecti… gap-debate-20260410-112958-9f149914 | open | 0.780 | pharmacology | 2026-04-10 | Open → |
| 10 | How do natural compounds mechanistically target ferroptosis pathways for breast… Natural compounds are identified as a promising new direction for ferroptosis-targeting drugs, but the abstract indicates the mechanistic basis for how these co… gap-pubmed-20260411-080111-283e4fe4 | open | 0.750 | pharmacology | 2026-04-11 | Open → |
| 11 | What are the long-term safety implications of chronic PARP1 modulation in the a… The Domain Expert raised concerns about cancer risk and cognitive impairment from PARP inhibitors, but no long-term CNS safety data exists. This knowledge gap i… gap-debate-20260410-112515-7046ef1d | open | 0.750 | pharmacology | 2026-04-10 | Open → |
| 12 | What is the therapeutic window between selective tau vesicle penetration and no… Safety concerns about membrane disruption were raised but not quantified. Determining the selectivity ratio between pathological and normal vesicles is essentia… gap-debate-20260410-100403-fc611008 | open | 0.750 | pharmacology | 2026-04-10 | Open → |
| 13 | Can pharmacological SREBP2 stabilization differentially rescue APOE4 versus APO… The theorist proposed fatostatin treatment should disproportionately affect APOE4 cells, but this prediction remains untested. Experimental validation would dis… gap-debate-20260417-033111-405e6fe3 | open | 0.750 | pharmacology | 2026-04-17 | Open → |
| 14 | How can small molecule therapeutics effectively cross the blood-spinal cord bar… Multiple promising ferroptosis targets were identified, but the debate repeatedly highlighted delivery challenges to the spinal cord compartment. This pharmacok… gap-debate-20260417-032955-73b6cfd5 | open | 0.750 | pharmacology | 2026-04-17 | Open → |
| 15 | What safety margins exist for membrane-disrupting nanobodies between therapeuti… The debate raised major safety concerns about widespread membrane disruption but provided no data on therapeutic windows. Understanding the selectivity ratio be… gap-debate-20260410-100359-892a3c3e | open | 0.750 | pharmacology | 2026-04-10 | Open → |
| 16 | Which metabolic pathways are modulated by current AD therapeutics to enable bio… The debate assumed metabolic biomarkers could distinguish therapeutic response but didn't establish which approved or pipeline therapeutics actually modulate me… gap-debate-20260410-111950-90112fd9 | open | 0.710 | pharmacology | 2026-04-10 | Open → |
| 17 | How do proposed therapeutic mechanisms avoid off-target effects across multiple… The theorist presented cell-type-specific therapies but the skeptic raised concerns about reference validity. The selectivity and safety profiles of targeting t… gap-debate-20260410-112607-72459883 | open | 0.710 | pharmacology | 2026-04-10 | Open → |
| 18 | Can kinase inhibitors achieve therapeutic effects through off-target complement… If validated, Alectinib's C1q interaction represents a novel mechanism where kinase inhibitors modulate innate immunity. This could reveal new therapeutic oppor… gap-debate-20260417-033041-af540ce7 | open | 0.700 | pharmacology | 2026-04-17 | Open → |