Title: Trabedersen-Drug Development using phosphorothioate antisese platform

Abstract:

Using the PS antisense platform we were able to target TGF-β2 without impacting on the β1 and β3, thus avoided the toxicity related to β1 knockdown. OT-101 lifts the immunosuppression in the tumor allowing the body to recognize the tumor as foreign.  Once that is in place-     everything else is easy.  For example- checkpoint inhibitor given to pts that don’t recognize the tumors as foreign would have no benefits.  The    antisense platform has the potential of replacing small molecules and mAbs as it is a single platform with abundance of clinical safety data and requiring minimum testing for backbone toxicity- much the same way mAb was so attractive as a platform. This has allowed for rapid drug development such as Milasen-  developed from lab to patient in less than year. FDA has approved many antisense drugs recently including: Fomivirsinen, Macugen, Mipomersen, Nusinersen/Spinraza, Exondys, Luxturna, Inotersen, and Patisiran.  One especially high profile early failure is Oblimersen (Genesense, Genta). Poor management of Oblimersen tainted the field especially PS DNA backbone primarily because clinical trials proceeded for more than a decade including multiple phase III trials- despite marginal efficacy data due to wrong target.

Biography:

Vuong Trieu, Ph.D. is the founder and chairman of Oncotelic and was appointed to the Company’s Board and to serve as Chairman of the Board and CEO of Mateon in connection with the Merger with Oncotelic. Dr. Trieu is an expert is drug repositioning with several high profile successes including Abraxane and Cynviloq- both are billion dollar drugs. He is leading Mateon effort to become the next generation pharmaceutical by leveraging AI data analytics to create a high value pipeline. You don’t know what you don’t know- but there is no excuse for not knowing.
 

Title: The effect of Streblus asper leaf extract on scopolamine induced memory impairment in zebrafish

Abstract:

Streblus asper (SA) belonging Moraceae family is well-known as a folk medicinal plant in Asian countries. This study aimed to investigate the effect of SA leaf extract on preventing memory impairment in zebrafish that is induced by scopolamine. This research using male zebrafish, Danio rerio. The zebrafish were divided into 6 groups including, control group, scopolamine (SCO) group, scopolamine plus rivastigmine 1.5 mg/kg (RV+SCO) group, scopolamine plus SA leaf extract at dose 200, 400 and 800 mg/kg (SA200+SCO, S400+SCO, and SA800+SCO) group, respectively. Spatial memory was evaluated by Colour biased appetite conditioning T-maze test while fear memory was measured by Inhibitory avoidance test. In spatial memory test, the results showed that the RV+SCO group had the best time spent in the green arm and the red arm ratio in the T-maze, followed by SA800+SCO, SA400+SCO, SA200+SCO, control, and SCO group, respectively. However, it had no statistically significant. In fear memory test, the result showed that zebrafishes received SA at dose 200, 400, and 800 mg/kg had significantly increased latency time as 21.75 ± 4.59, 23.75 ± 13.01, and 18.20 ± 18.84 min, respectively when compared to the SCO group (9.80 ± 10.45 min). These results suggested that SA leaf extract might prevent memory impairment in zebrafish especially in fear memory. These findings can be a part of the information for further research to develop SA extract to be the health products to prevent memory impairment or Alzheimer’s disease in the future.

Biography:

My name is Kanathip Singsai, 33 years old, I am a lecturer at Department of Pharmaceutical care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand. I graduated a Ph.D. in Pharmacology (Neuropharmacology) at the age of 29 years from Department of Pharmacology, Faculty of Medicine, Khon Kaen University. My research involves neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, and others related.

Title: Using targeted repurposing to discover novel neuroprotective treatments for Parkinson’s disease

Abstract:

Parkinson’s disease is a neurodegenerative disorder accompanied by motor symptoms which result from degeneration of dopaminergic neurons in the nigrostriatal pathway. While current treatments aimed at replenishing lost dopamine transmission help restore movement, these treatments do not combat the ongoing neurodegeneration so motor symptoms continue to progressively worsen. There currently remains no neuroprotective treatment for use in Parkinson’s disease. We previously reported that direct intracerbral infusion of fibroblast growth factor 20 (FGF20), a neurotrophic factor which supports dopaminergic neurones, was neuroprotective in the 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Given the difficulties associated with growth factor infusion in patients, we looked for an alternative way to boost endogenous FGF20 levels to achieve this neuroprotection. Specifically, we adopted a targeted repurposing approach to screen for candidate FDA-approved drugs with potential to enhance endogenous FGF20 production. In silico interrogation of the Broad Institute’s Connectivity Map database revealed 16 candidate drugs that increased FGF20 transcription, were blood brain barrier penetrant and not contra-indicated for use in Parkinson’s disease. Through in-vitro screening, 4 drugs were found to significantly elevate FGF20 protein levels, as determined by ELISA, in both MCF-7 cells and ventral mesencephalic primary cultures. Of these, salbutamol and triflusal significantly elevated FGF20 levels in the nigrostriatal tract in rats treated orally for 7 days and afforded a modest but significant protection against against nigral cell loss in the 6-OHDA-lesion rat. These daa support targeted repurposing as a powerful strategy to help the timely identification of neuroprotective treatments for Parkinson’s disease.  

Biography:

Susan Duty completed her PhD from the University of Manchester and undertook postdoctoral studies at the Universities of Sydney and Manchester before achieving an academic appointment at King’s College London in 1995. Susan is now Head of Department of Pharmacology & Therapeutics and Primary Investigator in the Wolfson Centre for Age-Related Diseases. She has published more than 49 papers and is a long-standing committee member of the British Pharmacological Society. Research in Susan’s laboratory is currently funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No 764860, Parkinson’s UK and Innovate UK.