Biotherapies group

Contacts

Stéphane Palfi Group leader, PU-PH Stéphane Palfi

Tél.: +33-(0)1 49 81 22 03
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Research topics :

 

The team brings together neurosurgeons, neurologists, psychologists, neuropsychologists, researchers and teacher-researchers working in the field of translational therapeutic innovation in functional neurosurgery, for the treatment of neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease), psychiatric diseases (Obsessive Compulsive Disorders and drug-resistant depressions) and brain tumors. Several lines of research are emerging: a line of neuromodulation of function to restore damaged function, a line of preservation of function during neurosurgical interventions by innovative perioperative brain mapping, a line of research on invasive biomarkers, on tools for detection of Beta particles in tumor exeresis as well as in biotherapies including cell therapy and gene therapy.

 

Neuromodulation of the injured function is done in the team by biotherapies such as dopamine-restoring enzyme gene therapy or cell therapy or optogenetics, as well as by deep electrical brain stimulation or vagus nerve stimulation. In a translational research approach, the team uses a variety of animal models, ranging from rodents to non-human primates and including ovines.

 

The concern for preservation of function during neurosurgical interventions led to the collaborative creation of the concept of awake and sleeping surgery based on innovative functional neuroimaging, lesional-mapping and magnetic brain stimulation techniques.

 

Translational Team Research:

 

 

RECENT RESULTS :

 

 

Lentiviral gene therapy for the treatment of Parkinson’s disease (Palfi et al., Lancet 2014)

 

 

 

 

 

 

 

 

 

 

 

 

 

Neuromodulation of cortico-subcortical projections by Optogenetics after retrograde gene transport by viral vector (Senova…Palfi, Scientific Reports Nature 2018)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Lesional network mapping: anatomical-functional connectivity of brain regions with brain tumors causing secondary manic syndromes (Cotovio….Senova et al., J of Clin Investigation 2020)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Sleepy awake surgery: multimodal brain mapping to preserve function during tumor removal in eloquent areas (Senova, ….Palfi… et al, Frontiers in Neuroscience 2021)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COLLABORATIONS:

The team collaborates with Prof. Antoine Chaillet, mathematician at Ecole Centrale-Supélec, for the development of closed-loop brain stimulation and with Prof. Jean-Pascal Lefaucheur, neurophysiologist at Henri Mondor University Hospital, for the pre-operative brain mapping by navigated TMS

The team collaborates with UCL, Cambridge UK in the framework of the dopamine gene therapy research program.

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Selected publications

Senova S, Lefaucheur JP, Brugières P, Ayache SS, Tazi S, Bapst B, Abhay K, Langeron O, Edakawa K, Palfi S, Bardel B. Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surgical Resection.

Front Hum Neurosci. 2021 Feb 25;15:646268. doi: 10.3389/fnhum.2021.646268. PMID: 33716700; PMCID: PMC7947337.

Tremblay S, Acker L, Afraz A, Albaugh DL, Amita H, Andrei AR, Angelucci A, Aschner A, Balan PF, Basso MA, Benvenuti G, Bohlen MO, Caiola MJ, Calcedo R, Cavanaugh J, Chen Y, Chen S, Chernov MM, Clark AM, Dai J, Debes SR, Deisseroth K, Desimone R, Dragoi V, Egger SW, Eldridge MAG, El-Nahal HG, Fabbrini F, Federer F, Fetsch CR, Fortuna MG, Friedman RM, Fujii N, Gail A, Galvan A, Ghosh S, Gieselmann MA, Gulli RA, Hikosaka O, Hosseini EA, Hu X, Hüer J, Inoue KI, Janz R, Jazayeri M, Jiang R, Ju N, Kar K, Klein C, Kohn A, Komatsu M, Maeda K, Martinez-Trujillo JC, Matsumoto M, Maunsell JHR, Mendoza-Halliday D, Monosov IE, Muers RS, Nurminen L, Ortiz-Rios M, O'Shea DJ, Palfi S, Petkov CI, Pojoga S, Rajalingham R, Ramakrishnan C, Remington ED, Revsine C, Roe AW, Sabes PN, Saunders RC, Scherberger H, Schmid MC, Schultz W, Seidemann E, Senova YS, Shadlen MN, Sheinberg DL, Siu C, Smith Y, Solomon SS, Sommer MA, Spudich JL, Stauffer WR, Takada M, Tang S, Thiele A, Treue S, Vanduffel W, Vogels R, Whitmire MP, Wichmann T, Wurtz RH, Xu H, Yazdan-Shahmorad A, Shenoy KV, DiCarlo JJ, Platt ML. An Open Resource for Non-human Primate Optogenetics.

Neuron. 2020 Dec 23;108(6):1075-1090.e6. doi: 10.1016/j.neuron.2020.09.027. Epub 2020 Oct 19. PMID: 33080229; PMCID: PMC7962465.

Cotovio G, Talmasov D, Barahona-Corrêa JB, Hsu J, Senova S, Ribeiro R, Soussand L, Velosa A, Silva VCE, Rost N, Wu O, Cohen AL, Oliveira-Maia AJ, Fox MD. Mapping mania symptoms based on focal brain damage.

J Clin Invest. 2020 Oct 1;130(10):5209-5222. doi: 10.1172/JCI136096. PMID: 32831292; PMCID: PMC7524493.

Barahona-Corrêa JB, Cotovio G, Costa RM, Ribeiro R, Velosa A, Silva VCE, Sperber C, Karnath HO, Senova S, Oliveira-Maia AJ. Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis.

Transl Psychiatry. 2020 May 12;10

Senova S, Fomenko A, Gondard E, Lozano AM. Anatomy and function of the fornix in the context of its potential as a therapeutic target.

J Neurol Neurosurg Psychiatry. 2020 May;91(5):547-559. doi: 10.1136/jnnp-2019-322375. Epub 2020 Mar 4. PMID: 32132227; PMCID: PMC7231447.

Bachoud-Lévi AC; on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group. Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial.

Mov Disord. 2020 Aug;35(8):1323-1335. doi: 10.1002/mds.28201. Epub 2020 Jul 15. PMID: 32666599.

Senova S, Mallet L, Gurruchaga JM, Rabu C, Derosin M, Yelnik J, Brugieres P, Pelissolo A, Palfi S, Domenech P. Severe Obsessive-Compulsive Disorder Secondary to Neurodegeneration With Brain Iron Accumulation: Complete Remission After Subthalamic Nuclei Deep Brain Stimulation.

Biol Psychiatry. 2020 Jun 15;87(12):e39-e41. doi: 10.1016/j.biopsych.2019.07.006. Epub 2019 Aug 28. PMID: 31472980.

Badin RA, Binley K, Van Camp N, Jan C, Gourlay J, Robert C, Gipchtein P, Fayard A, Stewart H, Ralph GS, Lad Y, Kelleher M, Loader J, Hosomi K, Palfi S, Mitrophanous KA, Hantraye P. Gene Therapy for Parkinson's Disease: Preclinical Evaluation of Optimally Configured TH:CH1 Fusion for Maximal Dopamine Synthesis.

Mol Ther Methods Clin Dev. 2019 Jul 16;14:206-216. doi: 10.1016/j.omtm.2019.07.002. PMID: 31406701; PMCID: PMC6685641.

Senova S, Chaillet A, Lozano AM. Fornical Closed-Loop Stimulation for Alzheimer's Disease.

Trends Neurosci. 2018 Jul;41(7):418-428. doi: 10.1016/j.tins.2018.03.015. Epub 2018 May 4. PMID: 29735372.

Palfi S, Gurruchaga JM, Lepetit H, Howard K, Ralph GS, Mason S, Gouello G, Domenech P, Buttery PC, Hantraye P, Tuckwell NJ, Barker RA, Mitrophanous KA. Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease.

Hum Gene Ther Clin Dev. 2018 Sep;29(3):148-155. doi: 10.1089/humc.2018.081. PMID: 30156440; PMCID: PMC6157351.