Thera’s technology represents a breakthrough in understanding the up-regulatory mechanisms behind the neuronal response to toxic or degenerative insults linked to the direct and indirect modulation of mitochondrial viability. Our technology leverages the activation of a protective pathway rather than focusing on a single defective enzyme or toxic molecule.
Our small molecules are the first compounds that induce a selective up-regulation of NF-κB p65 expression in brain cells.

The positive effect elicited by our compounds is intimately dependent on the selectively activation of the NF-κB p65 subunit and on the specificity of the targets engaged.
We have identified in our library seven regenerative compounds that activate the NFκB p65 subunit exclusively in neuronal cells via a non-canonical mechanism and without inducing pro-inflammatory effects classically associated with the activation of the cytokine receptor pathways (triggered by I-κB phosphorylation and subsequent I-κB degradation).

Their efficacy is mediated by the cross-functional interaction between the direct neurotrophic and transcriptional effects induced by NF-κB p65 activation and the mitochondrial-mediated cell viability and protein functionality regulated by the MnSOD. The mechanism of action of our compounds is not to ascribe merely to a compensatory mechanism of SOD2 but to an upstream multifactorial regulation associated with a more substantive role of the whole pathway.


Selective activation of the NF-κB pathway is critical for cell functioning/viability (up-regulatory effect) with a direct effect on key pathogenic targets of degeneration.

Nuclear Factor-κB (NF-κB) is a transcription factor particularly important in the central nervous system, where it mediates key effects associated with neuronal longevity and activation of different neurotrophins favoring survival of neurons. Furthermore, NF-κB strongly up-regulates an important mitochondrial enzyme, manganese superoxide dismutase (MnSOD), which is not only a key element in quenching and eliminating free radicals (ROS) from neuronal cells but, more importantly, has a critical role in modulating mitochondrial functioning.

Up-regulation of NF-κB has been recognized as a potential therapeutic target for many neurologic conditions. In ALS, TBI, and other neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's Diseases, transcription deficit has been associated with the pathogenic mechanism of the disease resulting in ROS-induced toxicity, mitochondrial malady, protein misfolding damage, and neurotrophin deficit.


The pathogenesis of neurodegenerative diseases involves the impairment/deficit of important components of brain functionality, including transduction deficit, protein misfolding, axonal dendritic degeneration, mitochondrial malady, and oxidative toxicity.

Our technology impacts these diseases with regenerative and potentially disease-modifying effects on three of their most important (and acknowledged) pathogenic components:

mitochondrial viability/oxidative toxicity:
   • through the increased expression of MnSOD
cell functioning:

through protein folding and anti-aggregation activity Ð our compounds induce expression of several DNAs coding for chaperone activity in many other proteins

   • through the expression/release of neurotrophins