Peptide therapy for treatment of epilepsy

Epilepsy is one of many neurological diseases that dramatically reduce quality of life and can lead to devastating outcomes in patients that are refractory to conventional therapies. Thyrotropin releasing hormone is a well-known endocrine hormone as part of the hypophysiotropic axis but also exerts a powerful anticonvulsant effect if it can be delivered to the epileptic region of the brain. The primary characteristic limiting use of thyrotropin releasing hormone in epilepsy is high susceptibility to endopeptidase metabolism if delivered orally or intravenously, as well as its inability to cross the blood brain barrier. Using the classical rat kindling model, the Veronesi Lab demonstrates both an anticonvulsant and enti-epileptic effect for thyrotropin releasing hormone using an intranasal approach. In addition, the lab demonstrates in vitro that thyrotropin releasing hormone exerts its anticonvulsant effects through modulation of the metabotropic glutamate receptor.
  • Publications

    Veronesi MC, Yard M, Jackson J, Lahiri DK and Kubek MJ. An analog of thyrotropin-releasing hormone (TRH) is neuroprotective against glutamate-induced toxicity in fetal rat hippocampal neurons in vitro. Brain Res. 2007 Jan 12;1128(1):79-85. PMID: 17125753.

    Veronesi MC. Neuropeptide Treatment in Epilepsy: An Intranasal Approach. Doctoral dissertation, Indiana University, 2008.

    Veronesi MC, Aldouby Y, Domb AJ and Kubek MJ. Thyrotropin-releasing hormone d,l polylactide nanoparticles (TRH-NPs) protect against glutamate toxicity in vitro and kindling development in vivo. Brain Res. 2009 Dec;15(1303):151-60. PMID: 19766611.

    Kubek MJ, Domb AJ and Veronesi MC. Attenuation of kindled seizures by intranasal delivery of neuropeptide-loaded nanoparticles. Neurotherapeutics. 2009 Apr;6(2):359-71. PMID: 19332331.

In the news

Veronesi’s graphic was previously included on the cover of the Journal Epilepsia for his work on reducing seizures in a preclinical model of epilepsy using a novel surgical approach to gain access to the olfactory region in the most posterior part of the nasal cavity. This work comprised a critical portion of his dissertation work as an MD/ PhD student from 2002 through 2010.