Lead program

small molecule - big impact


Our lead developing program, MIC-083, focuses on innovative microRNA medicine for the treatment of major depression disorder (MDD) and treatment-resistant depression, both with high unmet medical need.

The development strategy of MIC-083 program is to replenish the endogenous microRNA-135 level in a microRNA replacement therapy fashion. microRNA-135 levels are significally reduced in brains of suicide victims and in the blood of depressed patients -studies showed.

Together with an overwhelming data demonstrating a direct involvement of this microRNA in anxiety and depression models and its ability to target several key genes that are associated with neuropsychatric disorders, microRNA-135 is been positioned as a key component that has the capability to regulate entire biological pathway that is pathogenically disrupted in depressed patient.

Dual activity for treatment
resistant depression

  • 5-Hydroxytryptamine Receptor 1A (HTR1A) has a dual and opposite effect in depression and anxiety depending on location: suppression of HTR1A autoreceptors located in presynaptic neurons in the DRN enhances stress resilience/antidepressant response; whereas, reductions in post-synaptic HTR1A heteroreceptors are associated with depression and anxiety.
  • Depressed patients and suicide victims show increased levels of presynaptic HTR1A autoreceptors which correlate with resistance to treatment with antidepressant drugs.
  • The widely common HTR1A rs6295 polymorphism has been associated with increased levels of the presynaptic autoreceptors, leading to depression, suicide and SSRI resistance.
  • Reduction in serotonin transporter (SERT) levels following SSRI treatment produces an increase in extracellular free serotonin 5-hydroxytryptamine (5-HT) , that activates HTR1A autoreceptors which in turn reduce neuronal firing – a mechanism that is proposed to underlying treatment resistant depression (TRD).
  • MIC-083 is a single therapy that hits both targets and– unlike other agents- avoids inhibition of post-synaptic heterorecpetor HTR1A and instead specifically targets presynaptic neurons. This dual effect makes MIC-083 a promising therapy for TRD.

> Administration of a oligonucleotide conjugated using miCure’s technology and a similar MOA was compared side by side to Fluoxatine i.p. treatment. The results demonstrated that 4 days of the new compound were enough to reach the same serotonin levels seen following 14 days of treatment with SSRIs.

Unique mechanism
of action with potential for
an earlier treatment onset

  • Unlike SSRIs, MIC-083 doesn’t simply blocks the serotonin transporter but reduces the amount of the transporter to what expect to be a 50% reduction.
  • The time course of 5-HT1A autoreceptor desensitization follows the latency for clinical response to SSRIs, suggesting that reduced 5-HT1A autoreceptor levels might shorten the latency.