NOVEL GLUTAMATE TRANSPORTER ACTIVATORS AND METHODS USING SAME

PAGE TITLE

Neuroprotective agent for Parkinson’s Disease

 

PAGE SUMMARY

Parkinson’s Disease (PD) is a progressive neurological disorder whose prevalence increases with age and certain genetic predispositions.  It is estimated that 7-10 million people are affected by Parkinson’s Disease worldwide, with 1 million in the United States.  Currently, there are no small molecule drugs to halt or reverse the progression of PD.  The gold standard therapy for treating the symptoms of PD is dopamine replacement therapy with Levodopa (L-dopa).  However, 60-80% of patients treated with L-dopa develop complications, including a severe movement disorder called L-dopa-induced dyskinesia.

 

To address the unmet need of pharmaceutical interventions that can halt the progression of Parkinson’s Disease, researchers at Drexel University have developed GT951, a novel small molecule activator of glutamate transporter GLT-1 / excitatory amino acid transporter EAAT2.  GT951 confers neuroprotection by scavenging out excess glutamate to prevent excitotoxicity and subsequent neurodegeneration.  In preliminary studies, GT951 has demonstrated high specificity to GLT-1 and sub-nanomolar efficacy in removing glutamate from the synapse.  A pilot efficacy study in a rodent PD model demonstrated that GL951 can prolong the time taken to form lesions and significantly reduce disease severity.  GT951 is being optimized for pharmacokinetics, safety, and toxicology to develop a preclinical candidate for GLP studies.

 

APPLICATIONS

TITLE: Applications

 

Neuroprotective and disease-modifying agent for Parkinson’s Disease

Potential to halt disease progression

Reduce risk of dyskinesia

 

ADVANTAGES

TITLE:Advantages

 

Envisioned product of orally available drug

Small molecule activator of GLT-1/EAAT2

Reduce excitotoxicity in brain

Delay use of L-dopa therapy to prevent ON-OFF and L-dopa-induced dyskinesia

 

IP STATUS

Intellectual Property and Development Status

Pending PCT application PCT/US2018/013867

https://patents.google.com/patent/WO2018132829A1/en?oq=PCT%2fUS2018%2f013867

 

PUBLICATIONS

References

Kortagere S. et al.  Identification of Novel Allosteric Modulators of Glutamate Transporters.  ACS Chemical Neuroscience, 2018, 9(3), p. 522-534.

https://pubs.acs.org/doi/10.1021/acschemneuro.7b00308

 

 

Contact Information

 

Robert McGrath, Ph.D.

Sr. Associate Vice Provost

215-895-0303

rbm26@drexel.edu

 

Patent Information: