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David R. Lynch, MD, PhD
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Professor of Neurology
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Department: Neurology
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Graduate Group Affiliations
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- Neuroscience 6a
- Pharmacology 6b
- Cell and Molecular Biology e
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Contact information
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502 Abramson Center
46 Children's Hospital of Philadelphia
Philadelphia, PA 19104
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46 Children's Hospital of Philadelphia
Philadelphia, PA 19104
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Office: 2155902242
30 Fax: 2155903779
30 Lab: 2155901451
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30 Fax: 2155903779
30 Lab: 2155901451
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Email:
LYNCHD@mail.MED.UPENN.EDU
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LYNCHD@mail.MED.UPENN.EDU
Links
3f Neuroscience graduate group faculty webpage.
4a Review of Friedreich ataxia
a6 Review of Friedreich Ataxia for patients and physicians
40 Pharmacological Sciences graduate group faculty webpage.
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3f Neuroscience graduate group faculty webpage.
4a Review of Friedreich ataxia
a6 Review of Friedreich Ataxia for patients and physicians
40 Pharmacological Sciences graduate group faculty webpage.
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Education:
21 9 B.S. 32 (Molecular Biophysics and Biochemistry) c
25 Yale College, 1981.
21 a Ph.D. 19 (Neuroscience) c
31 Johns Hopkins University, 1988.
21 9 M.D. 19 (Neuroscience) c
31 Johns Hopkins University, 1988.
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Permanent link21 9 B.S. 32 (Molecular Biophysics and Biochemistry) c
25 Yale College, 1981.
21 a Ph.D. 19 (Neuroscience) c
31 Johns Hopkins University, 1988.
21 9 M.D. 19 (Neuroscience) c
31 Johns Hopkins University, 1988.
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17 NMDA receptors
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12 KEY WORDS:
1c glutamate, receptor
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1b RESEARCH TECHNIQUES
1a Molecular biology
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3d6 Excitotoxicity is a unique pathophysiological mechanism which is involved in cerebral ischemia, secondary damage in neuronal trauma, and neuronal damage from prolonged seizures. The deleterious effects from excitotoxicity result from calcium entry through a specific glutamate receptor, the N-methyl D-aspartate (NMDA) receptor. NMDA receptor antagonists act both as neuroprotective agents against excitotoxicity and as anticonvulsants in animals, but human clinical trials with the most potent agents have been complicated by side effects including psychosis. Much evidence indicates the presence of multiple types of NMDA receptors in the brain, and evidence from our laboratory suggests that different subtypes play different roles in physiological and excitotoxic processes. If one could develop therapeutic agents which are selective for the subtypes involved in excitotoxicity, one could more readily utilize NMDA receptor antagonists for treatment of human diseases.
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3c0 We use a systematic approach to examine the subtype specific physiological and pharmacological properties of NMDA receptors. NMDA receptors are created in tissue culture expression systems, and their properties are studied biochemically, pharmacologically and physiologically to correlate receptor properties in these systems with such properties in vivo. We have previously shown that different NMDA receptor subtypes have distinct pharmacologies and produce different changes in intracellular calcium. In the near future we will extend these examinations of subtype specific properties to include the modulation of other intracellular messengers such as nitric oxide and examine the effect of such properties on excitotoxicity. Combined with our studies on the pharmacological specificity of NMDA receptor subtypes, this will facilitate the development of therapeutic agents directed to those NMDA receptors which play crucial roles in excitotoxicity.
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Description of Research Expertise
23 RESEARCH INTERESTS17 NMDA receptors
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12 KEY WORDS:
1c glutamate, receptor
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1b RESEARCH TECHNIQUES
1a Molecular biology
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18 RESEARCH SUMMARY
3d6 Excitotoxicity is a unique pathophysiological mechanism which is involved in cerebral ischemia, secondary damage in neuronal trauma, and neuronal damage from prolonged seizures. The deleterious effects from excitotoxicity result from calcium entry through a specific glutamate receptor, the N-methyl D-aspartate (NMDA) receptor. NMDA receptor antagonists act both as neuroprotective agents against excitotoxicity and as anticonvulsants in animals, but human clinical trials with the most potent agents have been complicated by side effects including psychosis. Much evidence indicates the presence of multiple types of NMDA receptors in the brain, and evidence from our laboratory suggests that different subtypes play different roles in physiological and excitotoxic processes. If one could develop therapeutic agents which are selective for the subtypes involved in excitotoxicity, one could more readily utilize NMDA receptor antagonists for treatment of human diseases.
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3c0 We use a systematic approach to examine the subtype specific physiological and pharmacological properties of NMDA receptors. NMDA receptors are created in tissue culture expression systems, and their properties are studied biochemically, pharmacologically and physiologically to correlate receptor properties in these systems with such properties in vivo. We have previously shown that different NMDA receptor subtypes have distinct pharmacologies and produce different changes in intracellular calcium. In the near future we will extend these examinations of subtype specific properties to include the modulation of other intracellular messengers such as nitric oxide and examine the effect of such properties on excitotoxicity. Combined with our studies on the pharmacological specificity of NMDA receptor subtypes, this will facilitate the development of therapeutic agents directed to those NMDA receptors which play crucial roles in excitotoxicity.
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f5 Yameogo P, Aguilar S, Prakash TP, Rigo F, Lynch DR, Napierala JS, Napierala M.: Antisense oligonucleotide therapy for patients with Friedreich's ataxia carrying the c.165+5G>C splicing mutation. 4a Mol Ther Nucleic Acids. 36(3): 102617, Jul 2025.
13b Gunther, K, Profeta, V, Keita, M, Park, C, Wells, M, Sharma, S, Schadt, K Lynch, D. R.: Safety Monitoring of Omaveloxolone in Friedreich Ataxia: Results from one year of clinical treatment. Neurology and Therapy 14(3): 1105-1114, Jun 2025.
10f Mercado Ayón, E., Talgo, E., Flatley, L., Coulman, J., Lynch, D. R.: Neurochemical Alterations in the Cerebellum in Friedreich’s Ataxia Mouse Models. Experimental Neurology 386: 115176, Apr 2025.
13e Joseph, D.J., Mercado-Ayon, E., Flatley, L., Viaene, A. N., Hordeaux, J., Marsh, E. D., Lynch, D. R.: Functional Characterization of Parallel fiber-Purkinje Cell Synapses in two Friedreich’s Ataxia Mouse Models. Cerebellum 24(2): 42, Feb 2025.
a6 Eshaghi, K., Rao, P., Shen, M., Lynch, D. R.: Genetic and Phenotypic Variability in Siblings with Friedreich Ataxia 62 Neurology Genetics 11(1): doi.org/10.1212/NXG.0000000000200234, Feb 2025.
11e Lynch, D.R., Subramony, S.H., Lin, K.Y., Mathews, K., Perlman, S., Yoon, G., Rummey, C.: Characterization of cardiac-onset initial presentation in Friedreich Ataxia. Pediatric Cardiology. 46(2): 379-382, Feb 2025.
e3 Lynch, DR: Propensity-matched analysis comparing omaveloxolone treatment to Friedreich ataxia natural history data. Future Neurology 2025 Notes: in press.
248 Georgiou-Karistianis N, Corben LA, Lock EF, Bujalka H, Adanyeguh I, Corti M, Deelchand DK, Delatycki MB, Dogan I, Farmer J, França MC Jr, Gabay AS, Gaetz W, Harding IH, Joers J, Lax MA, Li J, Lynch DR, Mareci TH, Martinez ARM, Pandolfo M, Papoutsi M, Parker RG, Reetz K, Rezende TJR, Roberts TP, Romanzetti S, Rudko DA, Saha S, Schulz JB, Subramony SH, Supramaniam VG, Lenglet C, Henry PG.: Neuroimaging biomarkers for Friedreich ataxia: a cross-sectional analysis of TRACK-FA. Ann Neurol 2025 Notes: in press.
f5 lawson, R, lynch DR, Perlman, S: The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis. J Neurol SCi 2025 Notes: in press.
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Selected Publications
287 Shiraishi DH, Saha S, Adanyeguh IM, Cocozza S, Corben LA, Deistung A, Delatycki MB, Dogan I, Gaetz W, Georgiou-Karistianis N, Graf S, Grisoli M, Henry PG, Jarola GM, Joers JM, Langkammer C, Lenglet C, Li J, Lobo CC, Lock EF, Lynch DR, Mareci TH, Martinez ARM, Monti S, Nigri A, Pandolfo M, Reetz K, Roberts TP, Romanzetti S, Rudko DA, Scaravilli A, Schulz JB, Subramony SH, Timmann D, França MC Jr, Harding IH, Rezende TJR; TRACK-FA Neuroimaging Consortium.: Automated Deep Learning-based Segmentation of the Dentate Nucleus Using Quantitative Susceptibility Mapping MRI. Radiol Artif Intell 2f . Page: e240478. Aug 2025.f5 Yameogo P, Aguilar S, Prakash TP, Rigo F, Lynch DR, Napierala JS, Napierala M.: Antisense oligonucleotide therapy for patients with Friedreich's ataxia carrying the c.165+5G>C splicing mutation. 4a Mol Ther Nucleic Acids. 36(3): 102617, Jul 2025.
13b Gunther, K, Profeta, V, Keita, M, Park, C, Wells, M, Sharma, S, Schadt, K Lynch, D. R.: Safety Monitoring of Omaveloxolone in Friedreich Ataxia: Results from one year of clinical treatment. Neurology and Therapy 14(3): 1105-1114, Jun 2025.
10f Mercado Ayón, E., Talgo, E., Flatley, L., Coulman, J., Lynch, D. R.: Neurochemical Alterations in the Cerebellum in Friedreich’s Ataxia Mouse Models. Experimental Neurology 386: 115176, Apr 2025.
13e Joseph, D.J., Mercado-Ayon, E., Flatley, L., Viaene, A. N., Hordeaux, J., Marsh, E. D., Lynch, D. R.: Functional Characterization of Parallel fiber-Purkinje Cell Synapses in two Friedreich’s Ataxia Mouse Models. Cerebellum 24(2): 42, Feb 2025.
a6 Eshaghi, K., Rao, P., Shen, M., Lynch, D. R.: Genetic and Phenotypic Variability in Siblings with Friedreich Ataxia 62 Neurology Genetics 11(1): doi.org/10.1212/NXG.0000000000200234, Feb 2025.
11e Lynch, D.R., Subramony, S.H., Lin, K.Y., Mathews, K., Perlman, S., Yoon, G., Rummey, C.: Characterization of cardiac-onset initial presentation in Friedreich Ataxia. Pediatric Cardiology. 46(2): 379-382, Feb 2025.
e3 Lynch, DR: Propensity-matched analysis comparing omaveloxolone treatment to Friedreich ataxia natural history data. Future Neurology 2025 Notes: in press.
248 Georgiou-Karistianis N, Corben LA, Lock EF, Bujalka H, Adanyeguh I, Corti M, Deelchand DK, Delatycki MB, Dogan I, Farmer J, França MC Jr, Gabay AS, Gaetz W, Harding IH, Joers J, Lax MA, Li J, Lynch DR, Mareci TH, Martinez ARM, Pandolfo M, Papoutsi M, Parker RG, Reetz K, Rezende TJR, Roberts TP, Romanzetti S, Rudko DA, Saha S, Schulz JB, Subramony SH, Supramaniam VG, Lenglet C, Henry PG.: Neuroimaging biomarkers for Friedreich ataxia: a cross-sectional analysis of TRACK-FA. Ann Neurol 2025 Notes: in press.
f5 lawson, R, lynch DR, Perlman, S: The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis. J Neurol SCi 2025 Notes: in press.
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