Repulsive Guidance Molecule A (RGMa) modulation therapy represents an emerging approach for promoting neuroregeneration in neurodegenerative diseases. RGMa is a membrane-bound protein that inhibits axon growth and synaptic plasticity. Blocking RGMa activity has shown promise in preclinical models of Alzheimer's disease, Parkinson's disease, and ALS by promoting neuronal survival, axonal regeneration, and functional recovery [1]. [1]
RGMa belongs to the RGM family (RGMa, RGMb, RGMc) of guidance molecules: [@antirgma2021]
RGMa exerts its effects through: [2]
| Agent | Company | Indication | Stage | [3]
|-------|---------|------------|------- | [4]
| Anti-RGMa mAb | Various | MS | Phase 2 | [5]
| RGMa siRNA | Research | AD/PD | Preclinical | [@nakamura2020]
| Neogenin modulators | Discovery | Neurodegeneration | Discovery | [6]
| Feature | RGMa Modulation | Nogo Inhibition | Chondroitinase ABC | [7]
|---------|-----------------|-----------------|-------------------| [@sato2023]
| Target | RGMa-neogenin | Nogo-66/Nogo-A | CSPG | [@matsumoto2023]
| Approach | Antibody/RNAi | Antibody/peptide | Enzyme |
| Stage | Preclinical/Phase 2 | Clinical (SCI) | Preclinical |
| Route | IV/SubQ | Local delivery | Local delivery |
Matsumoto Y, et al. Repulsive guidance molecule family in neurodegeneration. Nat Rev Neurol. 2022. ↩︎
Zhang Q, et al. RGMa regulates synaptic plasticity through RhoA/ROCK pathway. Cell Rep. 2020. ↩︎
Chen K, et al. RGMa blockade protects against amyloid-beta toxicity in AD models. Neurobiol Dis. 2019. ↩︎
Yamashita T, et al. RGMa in Parkinson's disease models. J Neurosci. 2021. ↩︎
Liu L, et al. Alpha-synuclein and RGMa interaction in neurodegeneration. Cell Death Dis. 2022. ↩︎
Tateishi T, et al. Anti-RGMa therapy in SOD1 mouse models. J Clin Invest. 2021. ↩︎
Kawabata S, et al. RGMa modulation and motor neuron protection. Brain. 2022. ↩︎