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​Dr. Tawfeeq Shekh-Ahmad: Investigating the basic mechanisms of ROS generation and the role of oxidative stress in epilepsy and neurological diseases; and developing targeted and auto-regulated antioxidant treatments to combat oxidative stress and related neurological disorders

Dr. Tawfeeq Shekh-Ahmad
I have acquired, within the recent years, a great interest in developing new treatments for drug-resistant epilepsy and other neurological disorders.
During my MSc and PhD studies at the School of Pharmacy at the Hebrew University, I focused principally on developing new chemical entities, evaluating the pharmacokinetics and pharmacodynamics of potential new antiepileptics and CNS drugs, as well as performing stereoselective pharmacokinetic/pharmacodynamic relationship studies of individual stereoisomers of chiral molecules.
In my postdoctoral research at the Department of Clinical and Experimental Epilepsy, University College London, I have worked on identifying potential antioxidant treatment strategies, centred around Nrf2 pathway (an endogenous regulator of antioxidant defence systems), and identifying sources of free radicals’ generation during seizures.
In addition, I’ve worked on developing gene therapies for the treatment of drug resistant epilepsy. Gene therapy refers to a set of techniques that introduce, overexpress, knock down or edit particular genes for therapeutic purposes. Viral vectors are engineered to encode the therapeutic genes or gene-editing constructs under the control of promoter elements that target their expression to specific cell types. As such, gene therapy theoretically provides what traditional pharmacotherapy cannot: a long-lasting intervention delivered to a predetermined population of target cells. Thus, gene therapy holds genuine clinical promise for the treatment of a wide variety of disorders, including epilepsy and other CNS diseases.
At my new lab at the School of Pharmacy in the Hebrew University, we investigate the processes and sources the contribute to the generation of free radicals and reactive oxygen species that lead to oxidative stress, and its relation with pathophysiological functions in CNS disorders, mainly in epileptogenesis (the process by which brain injury leads to chronic epilepsy) and established epilepsy.
In addition, we study novel gene therapy approaches that will be implemented in different rodent models, target genes and genetic approaches, to develop antioxidant gene therapy for targeting oxidative stress in CNS diseases.
The main advantage of our proposed approach is that it opens the possibility to modify only affected neurons/cells, and spares healthy cells in surrounding tissue. This opens a possibility for treatments in regions of the brain that are essential for function which cannot be surgically removed, and surmounts the issue of developing cell specificity of the treatments.

Research Interest:

  • Study the multiple neuroprotective effects of Keap1/Nrf2 pathway
  • Targeted drug delivery for CNS
  • AAV-based gene therapy for CNS diseases
  • Study the pharmacokinetics and pharmacodynamics of novel CNS active drugs
the multiple neuroprotective Effects of Nrf2