NST0037, a semi-synthetic statin, shows anti-excitotoxic and anti-epileptic effects by using a classic mouse model that causes seizures and excitotoxic neurodegeneration in the cerebral areas associated with Alzheimer's disease.

NST0037, a novel statin developed by NEURON BPh, can potentially be used as hypocholesterolemic, anti-epileptic, anticonvulsivant, antioxidant and neuroprotective compound for neurodegenerative and aging processes. NST0037 is potentially useful for the treatment and/or prevention of epilepsy, seizures, convulsive crises, neurodegenerative diseases and pathologic processes associated with abnormal oxidation.

Due to its hypocholesterolemic effect NST0037 can be also potentially used as a cardiovascular protectant agent to prevent and treat myocardial infarction, atherosclerosis, congenic cardiopathy, acquired cardiomyopathy, ischemic cardiopathy, hypertensive cardiopathy, valvopathys, myocardiopathys, blood disorders, etc.  

Statins are inhibitors of HMG-CoA-reductase and have recently been recognised for their anti-inflammatory and neuroprotective properties. From NEURON BPh we demonstrated the anti-excitotoxic and anti-epileptic effects of NST0037 by using a mouse model that causes seizures and excitotoxic neurodegeneration in the cerebral areas associated with Alzheimer's disease. Excitotoxicity is an important pathological mechanism underlying acute and delayed neuronal death and is secondarily associated with several neurodegenerative processes such as epilepsy, seizures, ischemia, Alzheimer's disease and Parkinson's disease. The systemic administration of glutamatergic agonists induces seizures, the production of reactive oxygen species, mitochondrial dysfunction, neuronal death and inflammation.  

In addition the company has evaluated NST0037 as neuroprotector in a neurodegeneration model produced by the administration of a glutamatergic agonist in mice. In these studies NST0037 clearly reduced the adverse effects that occur as a consequence of the administration of a neurotoxin. NST0037 administered before and after neurodegeneration, produced a significant reduction in the adverse effects caused by a glutamate analogue in the following ways:

 (i) an increase in the latency period (time of appearance of the first epileptic symptoms);

(ii) a decrease in the severity of the seizures according to Racine's scale, in which the      most effective way of administration and dose are defined. The effectiveness of NST0037 was comparable to specific antagonists.

(iii) a decrease in mortality levels associated with the administration of the neurotoxin;

(iv) a recovery of the structural integrity of the hippocampus;

(v) a decrease of the number of neurons in degeneration;

 (vi) a reduction in the levels of apoptosis in the hippocampus;

(vii) a decrease in reactive gliosis in the hippocampus;

(viii) a reduction in oxidative damage to the hippocampus.

 

 

 

Preclinical

Patent application EP09382051.2

NEURON BPh is actively looking for a collaborative/licensing partner for NST0037 and envisions a licensee-sponsored clinical trial.