HYBRID EVENT: You can participate in person at Orlando, USA or Virtually from your home or work.

6th Edition of International Conference on Neurology and Brain Disorders

October 24 -26, 2022

October 24 -26, 2022 | Orlando, Florida, USA
INBC 2022

Marianna Mekhaeil

Speaker at Neurology and Brain Disorders 2022 - Marianna Mekhaeil
Trinity college Dublin, Ireland
Title : Investigating novel therapies for metachromatic leukodystrophy, a fatal neurodegenerative disease

Abstract:

Metachromatic leukodystrophy (MLD) is a rare genetic disorder that affects the central nervous system white matter. MLD is caused by recessive mutations in ARSA encoding arylsulfatase A. Low activity of arylsulfatase A results in the accumulation of sulfatides in the central and peripheral nervous system leading to demyelination and chronic inflammation. The disease is classified in a late-infantile, juvenile and adult onset type based on the age of onset, all characterized by a variety of neurological symptoms (e.g. memory deficits, epilepsy), which eventually lead to death if untreated. There is no curative treatment for all types and stages, therefore there is an urgent need for novel therapeutic approaches. Olaparib is a poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor that has arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. PARP-1 inhibitors are noted to demonstrate notable neuroprotective effects in demyelinating disorders such as multiple sclerosis and Parkinson’s disease, further supporting the use of these drugs in demyelinating, neuroinflammatory, and neurodegenerative diseases. Our research investigates the ability of Olaparib to reverse sulfatides-induced demyelination and neuroinflammation in vitro, ex vivo, and in vivo. Our results are promising and so far, have showed that Olaparib rescues demyelination via modulation of PARP-1 expression in a mouse brain slice culture model. Moreover, Olaparib regulates microglia and astrocytes levels. Lastly Olaparib reduces sulfatides-induced inflammation by regulating astrocytes cytokines and chemo attractants release. These data strengthen a case for repurposing Olaparib for non-oncological indication, particularly in illnesses as MLD for which there are few therapeutic options.

What will audience learn from your presentation?

  1. Several severe and debilitating chronic indications with no alternative therapeutic options (e.g., leukodystrophies) represent a significant unmet clinical need and therefore remain candidates for urgent drug repurposing. In these indications, the currently available therapeutic options are extremely limited and of marginal efficacy. For indications of this type, treatment with PARP-1 inhibitors is a worth concept to consider.
  2. Drug repurposing has numerous advantages over conventional drug discovery approaches, including considerably cuts research and development (R&D) costs, reduced drug development timeline, as various existing compounds have already demonstrated safety in humans, it does not require Phase 1 clinical trials.
  3. The role of astrocytes in demyelination process is fundamental and not fully understood.

Biography:

Marianna Mekhaeil is a first year PhD student in Neuroscience at Trinity College Dublin, Ireland. She graduated in Pharmaceutical Biotechnology at the University of Statale di Milano, Italy. During her master’s degree, she had the opportunity to spend most of the time at the DZNE (Center for Neurodegenerative Disease, Bonn) in Germany. Marianna Mekhaeil is specifically interested in neurodegeneration, myelination, glial cells biology, and drug development with an overarching research goal to develop novel therapies and improve outcomes for patients with neurodegenerative pathologies. She has authored 1 publication named " Inhibition of microglial β-glucocerebrosidase hampers the microglia-mediated antioxidant and protective response in neurons" and 1 review entitled “Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases”.

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