FHND1002: A mRNA Translation Promotive and Axon Pro-regenerative Drug for Neuron-damage Diseases
Yongqiang Zhu1, Chenhui Li2
1Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd./ Nanjing Normal University, 2Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd.
Objective:

To develop FHND1002, a novel small molecule oral therapy that has exhibited promising preclinical efficacy in neuronal protection and functional recovery in models of neurodegenerative diseases and neuron trauma.

Background:

Parkinson's disease and motor dysfunction induced by trauma affect millions of patients, with a shortage of therapeutic drugs available. Studies highlight the efficacy of neuron protein synthesis or neuronal axon function improvement in alleviating motor dysfunction due to Parkinson's disease and neuronal injury. Our studies have demonstrated a new medicine, FHND1002, is capable of enhancing the synthesis of neuronal proteins and the regeneration of axons for neuron disease treatment.

Design/Methods:

Parkinson's disease models induced by MPTP in addition to hemi-dissection injuries to the spinal cord and sciatic nerve caused by trauma were created. Subsequent behavioural evaluations, electrophysiological measurements, histopathological analyses and transcriptomic analyses were performed.

Results:

Cellular assays showed that FHND1002 hindered eIF2α phosphorylation and stimulated protein synthesis in the Neuro2A cells. In the MPTP-induced model of Parkinson's disease, FHND1002 demonstrated significant improvement in motor function and reduction in loss of dopaminergic neurons and nerve fibres. In the model of spinal cord injury, FHND1002 significantly mitigated spinal cord injury-induced motor deficits. Finally, a sciatic nerve crush model was constructed and continuous administration of FHND1002 improved motor nerve function, increased the conduction rate of the sciatic nerve and maintained pain sensation in the injured limb 14 days after injury. 

Conclusions:

FHND1002 shows significant improvement in motor deficits resulting from Parkinson's disease, spinal cord injury, and sciatic nerve injury while maintaining neurological function related to the respective conditions. Additionally, FHND1002 is orally administered and can be taken once daily, thereby offering excellent neuroprotection. The drug is currently prepared for IND submission with NMPA and FDA for various indications, such as Parkinson's disease, spinal cord injury, and peripheral nerve injury.

10.1212/WNL.0000000000205577