Yissum - Research Development Company of the Hebrew University

SUPERDOPA: A New Small Molecule for the Treatment of Parkinson's Disease

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

A novel anti-apoptotic slow-release L-Dopa precursor
A small molecule (approximately the size of a tri-peptide) with multiple properties for treating Parkinson
(for parkinson and anti biofilm)
making the L-Dopa treatment last for many more years
Project ID : 7-2014-2989

Yissum - Research Development Company of the Hebrew University
Yissum - Research Development Company of the Hebrew University

Description of the technology

Keywords

Cell death, dopaminergic (DA) neurons, L-Dopa-induced dyskinesia (LID)

Current development stage

TRL3 - hypothesis testing and initial POC demonstrated in limited number of in-vitro models

Application

  • Parkinson’s Disease (PD) is a progressive neurodegenerative disease caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). As the disease progresses the number of dopaminergic neurons decreases.The most effective drug is L-Dopa (levodopa), which has remained the standard care of treatment in PD for more than 5 decades.Treatment with L-Dopa reverses akinesia in patients with PD and replenishes the missing dopamine but does not prevent cell death and is accompanied by an increase in involuntary aimless movements known as L-Dopa-induced dyskinesia (LID), which make L-Dopa ineffective.
  • Due to incomplete understanding of the molecular mechanisms involved in PD the focus is turned on targeting side effects of L-DOPA treatment.There is an unmet need to improve L-Dopa treatment and to prevent loss of dopaminergic neurons

Our Innovation

Novel L-Dopa small molecular weight derivatives (“SuperDopa” molecules – SD1, SD2) designed to protect dopaminergic neurons from cell death concomitantly with a slow-release replenishing of the missing dopamine in the PD brain

  • Prevent L-Dopa associated dyskinesia (LID) for which there is no approved drug
  • Lower the nitrosative /oxidative stress
  • Inactivate the mitogen-activated protein kinases (MAPKs), thus inhibiting the apoptotic pathways of the cells responsible for inflammatory consequences

  • Denitrosylate MEF2C, a major player in neuronal function and neuronal survival

Preliminary Results

SuperDopa (SD1) is very effective in reversing the oxidative stress induced by auranofin, an organo-gold compound that inhibits thioredoxin-reductase activity and elevates ROS in the cell

Increasing concentration of SD1 inhibits p38MAPK and ERK1/2 activity acting through the reversal of auranofin oxidizing effects in human neuronal SH-SY5Y cells

SD1 can also cross the blood brain barrier (BBB) and protect cognitive impairment following injury

Fig. 1 Reversal of oxidative stress induces p38MAPK activation –

(A) No effect on p38MAPK phosphorylation by L-Dopa,

(B) A significant reduction in p38 MAPK phosphorylation by SuperDopa (SD)

(SD=SuperDopa, AuF = auranofin)

Fig. 2 Reversal of oxidative stress induced MAPK ERK1/2 activation

(A)No effect by L-Dopa,

(B)A significant decrease by SuperDopa

(DA = L-Dopa, SD=SuperDopa, AuF = auranofin)

Opportunity

  • Small molecular-weight drug for the treatment of Parkinson's disease that affects more than 10 million people worldwide.
  • Better prognosis for PD patients and improving L-Dopa treatment.

Project manager

Mel Larrosa
VP Business Development Healthcare

Project researchers

Daphne Atlas
HUJI, Faculty of Science
The Alexander Silberman Institute for Life Sciences

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About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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