The ALK/ALKAL2 signaling axis, known to play a role in malignancies, has led to the development of ALK inhibitors for cancer therapy. Researchers at the University of Calgary have discovered that ALKAL2, the ligand for the anaplastic lymphoma kinase (ALK) receptor, is a biomarker of inflammation-induced nociceptor sensitization. ALKAL2 is upregulated in Transient Receptor Potential Vanilloid 1 (TRPV1) nociceptors in inflammation and ALK activation by ALKAL2 induces hyperalgesia. Knocking down ALKAL2 with antisense oligonucleotides and blocking ALK with clinically available compounds Crizotinib or Lorlatinib was effective in preventing persistent pain. Therefore, ALKAL2 and its receptor ALK, have been identified as novel targets for treating pain.
AREAS OF APPLICATION
- Therapeutics for the treatment of persistent pain conditions.
- ALK/ALKAL2 is a novel approach for treating persistent pain conditions.
- Ongoing research developing novel compounds targeting ALKAL2.
- Faster route to market: direct phase 2 clinical trial is feasible with Crizotinib and Lorlatinib, both therapeutics are FDA approved for cancer treatment.
- Easier route of drug administration with Lorlatinib: high potency and effectively crosses the blood brain barrier.
PUBLICATIONS AND RESOURCES
- PCT publication: WO2023082020A1
- Journal publication: Defaye M et al. (2022). The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain. J Clin Invest 132(12).
- Researcher profile: Dr. Christophe Altier