GeneGrafts - Our Technology
Home
The Technology
Based on the need for a more effective treatment modalities for excitable tissue disorders (e.g. Parkinsonís disease, Cardiac arrhythmias, etcí), we have developed a novel technology platform, that is based on transplantation of cell grafts, isolated from the patient own body, that express specific ion channels. The grafted cells integrate functionally and structurally with the target organ and their electrical properties are derived from the expressed ion channels. The target organ electrical properties are modulated in a predetermined way. This technology will be used for the treatment of neurological disorders and cardiac arrhythmias.

Parkinson's Disease

Long term drug treatment of Parkinson's disease (PD) is frequently associated with motor fluctuation. The most effective treatment for advanced PD patients is deep brain stimulation (DBS). However, DBS is associated with cognitive changes in up to 41% and with limited efficacy over the age of 70 years. The mechanisms that may cause gait impairment and postural instability after DBS include microlesion or stimulation interferences with cerebellothalamic pathways, pedunculopontine nuclei, or corticospinal tracts?all lying near the STN. These effects may be tolerated in younger patients who have physiologic reserve but may lead to worsening in the older patients who tend to develop gait disorders, with or without PD. Unfortunately, the majority of patients with advanced PD are 70 years old or more. GeneGrafts develops a treatment for advanced PD by transplantation of dermal fibroblasts to the basal ganglia nucleus - GPi. The fibroblasts integrate with the tissue and form structural and electrophysiological changes that are associated with desynchronization of the target pathologically overactive nucleus. Thus, GeneGrafts? product is not expected to produce electrical field affecting adjacent structures, and the needle needed for transplantation is in an order of magnitude smaller than the DBS electrode in diameter and therefore microlesions should be very limited. The company demonstrated the efficacy of this approach in multiple long-term studies (up to 12 months) on parkinsonian rats, and demonstrated the efficacy of this approach for the treatment of dyskinesia on Parkinsonian non-human primate at Emory School of Medicine, Atlanta.

References
  1. 1. J.P.M. Finberg, Z. Gluzman, M. Reshef, Y. Loboda, O. Mohsen, T. Bressler-Stramer, R. Miari, E. Vlodavsky, L. Gepstein, S. Marom, Y. Feld. Modulation of excessive neuronal activity by fibroblasts; potential use in treatment of Parkinson's disease.
    Restor Neurol Neurosci. 2010 Dec;28(6): 803-815.
  2. J.P.M. Finberg, S. Marom, M. Reshef , Z. Gluzman, O. Mohsen, Y. Feld. Normalization of 6-hydroxydopamine-induced rotational behavior by transplantation of dermal fibroblasts. 11th International Congress of Parkinson's disease & Movement Disorders, 2007.
    Circulation. 2002 Jan;105:522-529.
  3. Yair Feld, Meira Melamed-Frank, Izhak Kehat, Dror Tal, Shimon Marom, Lior Gepstein. Electrophysiological Modulation of Cardiomyocytic Tissue by Transfected Fibroblasts Expressing Potassium Channels: A Novel Strategy to Manipulate Excitability. Circulation. 2002 Jan;105:522-529.
    Am J Physiol Heart Circ Physiol. 2004 Mar, 286(3):H815-22.
  4. Gepstein L, Feld Y, Yankelson L. Somatic gene and cell therapy strategies for the treatment of cardiac arrhythmias.
    Am J Physiol Heart Circ Physiol. 2004 Mar, 286(3):H815-22.
  5. Yankelson L, Feld Y, Bressler-Stramer T, Itzhaki I, Huber I, Gepstein A, Aronson D, Marom S, Gepstein L. Cell Therapy for Modification of the Myocardial Electrophysiological Substrate. Circulation. 2008 Jan 22.
  6. H. Russmann, J. Ghika, J.-G. Villemure, B. Robert, J. Bogousslavsky, P. R. Burkhard and F. J.G. Vingerhoets. Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years .Neurology 2004;63;1952-1954.
  7. Temel Y, Kessels A, Tan S, Topdag A, Boon P, Visser-Vandewalle V. Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. .Parkinsonism Relat Disord. 2006 Jun;12(5):265-72. Epub 2006 Apr 18.