Palermo, 2016.10.04
A translational study resulting from a collaboration between Ri.MED Foundation, Policlinico Umberto I of Rome, La Sapienza University of Rome, and the University of Amsterdam* was published on Epilepsia Open, the open access journal of the International League Against Epilepsy.
Use of cannabis for therapeutic use in drug-resistant epilepsy: from a clinical case to the identification of a new molecule with anti-epileptic activity
Ri.MED scientist Pierangelo Cifelli, MD, PhD, is first co-author of this study describing how controlled administration of cannabis in a strongly drug-resistant patient was able to significantly reduce the number and severity of epileptic seizures and improve cognitive performance, with no side effects. Starting from the clinical observation of a patient, the cannabidivarin molecule and its possible mechanism of action were subsequently discovered in the laboratory.
Epilepsy is a pathological condition characterized by an abnormal electrical activity of the central nervous system. Epileptic seizures can spontaneously resolve in a few minutes, but at times they can repeat at close intervals creating a condition defined as status epilepticus that, especially when the seizures are of a convulsive kind, requires therapeutic action. In the most severe cases, the patients may need to be admitted in hospital in a critical care unit. Although access to pharmacological treatment has increased over recent years, approximately 30% of such patients are drug-resistant; their only option is surgery to remove the epileptogenic focus. This approach, however, is feasible only in selected cases.
The clinical case described in the study concerns a young man suffering from a very severe form of epilepsy (epileptic encephalopathy) with dozens of epileptic seizure every day. No pharmacological therapy can solve this condition, so the patient undergoes surgery, but to no benefit. As last possible treatment, his parents autonomously decide to try administering cannabis to him in the form of an herbal infusion. Within four days, his clinical conditions show a considerable reduction of the epileptic seizures and an improvement of his cognitive performance. Tests to assess the blood concentration of several cannabinoids, an accurate electroencephalography assessment, and cognitive tests are performed at the Department of Epileptology of Policlinico Umberto I. The blood tests show the presence of a still relatively unknown cannabinoid called cannabidivarin.
“From clinical observation,” explains Dr. Cifelli, “we progressed to the experimental phase highlighting a new mechanism of action concerning cannabidivarin. We were able to demonstrate how this molecule, devoid of psychoactive effects, is able to modulate the GABAergic response mediated by GABAA receptors”.
“The results of this study,” continues the Ri.MED researcher, “open up new interesting prospects. It’s important to continue research on the therapeutic potential of phytocannabinoids to fill the scientific gap of the last 40 years.”
Thanks to an agreement between RI.MED and La Sapienza University, Dr. Cifelli is currently conducting research at the latter’s Department of Physiology and Pharmacology led by Prof. Palma, where other projects are already in the pipeline. “Our intention is to study interactions between anti-epileptic drugs and phytocannabinoids and their potential use in strongly drug-resistant childhood epilepsy,” says Dr. Cifelli. “Research is the basis for studying the mechanisms of these molecules, and guide the development of a comprehensive therapy based on different drugs. This will involve verifying outcomes on a significant sample of patients, and this can only be done thanks to the collaboration between basic and clinical research.”
These words acknowledge the translational approach promoted by the Ri.MED Foundation: a model of public-private management supporting a collaboration between various Italian and foreign institutions, and between laboratories and patient care. Thanks to partners University of Pittsburgh, UPMC, and the Italian National Research Council (CNR), to its strategic international collaborations, and the selection of the most promising researchers, even before the opening of its research center in Sicily, Ri.MED Foundation has started to generate intellectual property, patents, and some true revolutions in clinical translation of scientific outcomes.
Dr. Cifelli will preview the study during the 10th Annual Ri.MED Scientific Symposium to be held in Palermo, Italy, on October 17.
*Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin
Alessandra Morano(1), Pierangelo Cifelli(2;3), Paolo Nencini(3) Letizia Antonilli(3), Jinane Fattouch(1), Gabriele Ruffolo(3), Cristina Roseti(4), Eleonora Aronica(5), Cristina Limatola(3), Carlo Di Bonaventura(1), Eleonora Palma(3), Anna Teresa Giallonardo (1)
- Department of Neurology and Psychiatry, Pasteur Institute-Cenci Bolognetti Foundation, University of Rome Sapienza, Italy
- Ri.MED Foundation, Palermo, Italy
- Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, University of Rome Sapienza, Italy
- IRCCS San Raffaele Pisana, Rome, Italy
- Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands Stichting Epilepsie Instellingen Nederland (SEIN-Heemstede), Amsterdam, the Netherlands
First published: 19 September 2016
Pierangelo Cifelli
Pierangelo Cifelli received his degree in Medicine and Surgery in 2002 at Tor Vergata University in Rome and received a visitors fellowship at McGill University in Montreal, Canada (2003-2004). He completed his PhD in neurobiology and cellular biophysics in 2007 at the University of Ferrara, Italy, and accepted a postdoctoral position in 2008 as a Ri.MED fellow, training at the University of Pittsburgh’s Department of Neuroscience, Pittsburgh (Mentor: Dr. Anthony Grace). Today Pierangelo is working at the University of Ferrara in the Department of Clinical and Experimental Pharmacology under the supervision of Dr Michele Simonato. Dr. Cifelli has extensive research experience in electrophysiology, including studies on epilepsy and the synaptic plasticity of the central nervous system in rodents. His current research activity includes studies on the neurogenesis of dopaminergic cells of adult transgenic mice, and on the action mechanism of dopaminergic of adult transgenic mice, and on the action mechanism of dopaminergic drugs.