Qatar Biomedical Research Institute QBRI

GO

Laboratory of Translational Neuroscience (LTN): Discovery of Biomarkers and Therapeutic Targets for Neurodegenerative and Neurodevelopmental Disorders

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This research team focuses on developing novel diagnostic tools for neurodegenerative diseases characterized by abnormal protein aggregation, and to develop new therapeutic strategies for their treatment. Such diseases include Parkinson's disease, Lewy body dementia (LBD), Alzheimer's disease, and multiple system atrophy (MSA). Their studies seek to develop novel biomarker diagnostic approaches and new therapeutics tools that can prevent the neurotoxic processes that contribute to the pathogenesis of these common neurodegenerative diseases, in particular the alpha-synucleopathies.

The team is commonly known for its research on biomarkers discovery and the development of disease-specific antibodies that can be used for diagnostic and/or therapeutic purposes. Their work extends from the development of novel diagnostic tools and their applications in clinical studies to technology transfer and commercialization.

The group also studies neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), which affects about 1% of the global population. ASD creates a significant public health burden in different communities including Qatar, where ASD incidence is about 1.4% in the growing young population. Their research efforts are aimed at discovering novel biomarkers that can be used as diagnostic tools for the early detection of ASD and could facilitate the development of clinical targets for early intervention.

Research Team

Current Projects

Latest Publications

  • Mesleh AG, Abdulla SA, and El-Agnaf O. Paving the Way toward Personalized Medicine: Current Advances and Challenges in Multi-OMICS Approach in Autism Spectrum Disorder for Biomarkers Discovery and Patient Stratification. Journal of Personalized Medicine. 2021 Jan. In Press.
  • Gupta V, Sudhakaran IP, Islam Z, Vaikath NN, Hmila I, Lukacsovich T, Kolatkar PR, El-Agnaf OMA. Expression, purification and characterization of α-synuclein fibrillar specific scFv from inclusion bodies. PLoS One. 2020 Nov 6;15(11):e0241773. doi: 10.1371/journal.pone.0241773.
  • Shalaby K, Aouida M, El-Agnaf O. Tissue-Specific Delivery of CRISPR Therapeutics: Strategies and Mechanisms of Non-Viral Vectors. Int J Mol Sci. 2020 Oct 5;21(19):7353. doi: 10.3390/ijms21197353.
  • Majbour N, El-Agnaf O. Plasma-derived therapy: can the survivors of COVID-19 help the defenseless? Diagnosis (Berl). 2020 Jul 21:/j/dx.ahead-of-print/dx-2020-0053/dx-2020-0053.xml. doi: 10.1515/dx- 2020-0053.
  • Hatton C, Reeve A, Lax NZ, Blain A, Ng YS, El-Agnaf O, Attems J, Taylor JP, Turnbull D, Erskine D. Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies. Acta Neuropathol Commun. 2020 Jul 9;8(1):103. doi: 10.1186/s40478-020-00985-8.
  • Volc D, Poewe W, Kutzelnigg A, Lührs P, Thun-Hohenstein C, Schneeberger A, Galabova G, Majbour N, Vaikath N, El-Agnaf O, Winter D, Mihailovska E, Mairhofer A, Schwenke C, Staffler G, Medori R. Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial. Lancet Neurol. 2020 Jul;19(7):591-600. doi: 10.1016/S1474-4422(20)30136-8.
  • Bourdenx M, Nioche A, Dovero S, Arotcarena ML, Camus S, Porras G, Thiolat ML, Rougier NP, Prigent A, Aubert P, Bohic S, Sandt C, Laferrière F, Doudnikoff E, Kruse N, Mollenhauer B, Novello S, Morari M, Leste-Lasserre T, Damas IT, Goillandeau M, Perier C, Estrada C, Garcia-Carrillo N, Recasens A, Vaikath NN, El-Agnaf OMA, Herrero MT, Derkinderen P, Vila M, Obeso JA, Dehay B, Bezard E. Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates. Sci Adv. 2020 May 13;6(20):eaaz9165. doi: 10.1126/sciadv.aaz9165. eCollection 2020 May.
  • Gupta V, Salim S, Hmila I, Vaikath NN, Sudhakaran IP, Ghanem SS, Majbour NK, Abdulla SA, Emara MM, Abdesselem HB, Lukacsovich T, Erskine D, El-Agnaf OMA. Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity. Sci Rep. 2020 May 18;10(1):8137. doi: 10.1038/s41598-020-65035-8.
  • Arotcarena ML, Dovero S, Prigent A, Bourdenx M, Camus S, Porras G, Thiolat ML, Tasselli M, Aubert P, Kruse N, Mollenhauer B, Trigo Damas I, Estrada C, Garcia-Carrillo N, Vaikath NN, El-Agnaf OMA, Herrero MT, Vila M, Obeso JA, Derkinderen P, Dehay B, Bezard E. Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates. Brain. 2020 May 1;143(5):1462-1475. doi: 10.1093/brain/awaa096.
  • Majbour NK, Aasly JO, Hustad E, Thomas MA, Vaikath NN, Elkum N, van de Berg WDJ, Tokuda T, Mollenhauer B, Berendse HW, El-Agnaf OMA. CSF total and oligomeric α-Synuclein along with TNF-α as risk biomarkers for Parkinson's disease: a study in LRRK2 mutation carriers. Transl Neurodegener. 2020 May 6;9(1):15. doi: 10.1186/s40035-020-00192-4.
  • Fayyad M, Erskine D, Majbour NK, Vaikath NN, Ghanem SS, Sudhakaran IP, Abdesselem H, Lamprokostopoulou A, Vekrellis K, Morris CM, Attems J, El-Agnaf OMA. Investigating the presence of doubly phosphorylated α-synuclein at tyrosine 125 and serine 129 in idiopathic Lewy body diseases. Brain Pathol. 2020 Jul;30(4):831-843. doi: 10.1111/bpa.12845.
  • Fayyad M, Majbour NK, Vaikath NN, Erskine D, El-Tarawneh H, Sudhakaran IP, Abdesselem H, El-Agnaf OMA. Generation of monoclonal antibodies against phosphorylated α-Synuclein at serine 129: Research tools for synucleinopathies. Neurosci Lett. 2020 Apr 23;725:134899. doi: 10.1016/j.neulet.2020.134899.
  • Ardah MT, Ghanem SS, Abdulla SA, Lv G, Emara MM, Paleologou KE, Vaikath NN, Lu JH, Li M, Vekrellis K, Eliezer D, El-Agnaf OMA. Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts. BMC Complement Med Ther. 2020 Mar 6;20(1):73. doi: 10.1186/s12906- 020-2849-1.
  • Taguchi T, Ikuno M, Hondo M, Parajuli LK, Taguchi K, Ueda J, Sawamura M, Okuda S, Nakanishi E, Hara J, Uemura N, Hatanaka Y, Ayaki T, Matsuzawa S, Tanaka M, El-Agnaf OMA, Koike M, Yanagisawa M, Uemura MT, Yamakado H, Takahashi R. α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson's disease model. Brain. 2020 Jan 1;143(1):249-265. doi: 10.1093/brain/awz380.
  • Erskine D, Reeve AK, Polvikoski T, Schaefer AM, Taylor RW, Lax NZ, El-Agnaf O, Attems J, Gorman GS, Turnbull DM, Ng YS. Lewy body pathology is more prevalent in older individuals with mitochondrial disease than controls. Acta Neuropathol. 2020 Jan;139(1):219-221. doi: 10.1007/s00401-019-02105-w.
  • Oosterveld LP, Verberk IMW, Majbour NK, El-Agnaf OM, Weinstein HC, Berendse HW, Teunissen CE, van de Berg WDJ. CSF or serum neurofilament light added to α-Synuclein panel discriminates Parkinson's from controls. Mov Disord. 2020 Feb;35(2):288-295. doi: 10.1002/mds.27897
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