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
- 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.
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.