Project title: “Protection Against Parkinson’s Disease”

Dates of Project Initiation and Completion: [June 2015] – [2019]

Resulting Publications:

(1) Ahmed Negida, Ahmed Menshawy, Gehad El Ashal, Yasmin Kamel, Yasmein Hani, Samar Elghonemy, Yasmin Hegazy, Samar Fouda, Yomna Rashad: Coenzyme Q10 for Patients with Parkinson’s Disease: A Systematic Review and Meta-Analysis. CNS & neurological disorders drug targets; 01/2016; 14(1)., DOI:10.2174/1871527314666150821103306

(2) Ahmed Negida, Mohamed Elfil, Attia Attia, Eslam Farahat, Mohamed Gabr, Ahmed Essam, Hussein Ahmed, Doaa Attia: Caffeine; the forgotten potential for Parkinson’s disease. CNS & neurological disorders drug targets 01/2017; 15.

(3) Abdelrahman Ibrahim Abushouk, Ahmed Negida, Rasha Abdelsalam Elshenawy, Hossam Zein, Ali M Hammad, Ahmed Menshawy, Wael M Y Mohamed: C-Abl Inhibition; A Novel Therapeutic Target for Parkinson’s Disease. CNS & neurological disorders drug targets; 06/2017; 16., DOI: 10.2174/1871527316666170602101538

(4) Abdelrahman Ibrahim Abushouk, Ahmed Negida, Hussien Ahmed, Mohamed M. Abdel-Daim: Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: Future applications in Parkinson’s disease. Biomedicine & pharmacotherapy; 11/2016; 85., DOI: 10.1016/j.biopha.2016.11.074

(5) Kamal Awad, Abdelrahman Ibrahim Abushouk, Ahmed Helal AbdelKarim, Maged Mohammed, Ahmed Negida, Ali S. Shalash: Bee venom for the treatment of Parkinson’s disease: How far is it possible? Biomedicine & pharmacotherapy; 07/2017; 91:295-302., DOI: 10.1016/j.biopha.2017.04.065

(6) Attia Attia, Hussien Ahmed, Mohamed Gadelkarim, Mahmoud Morsi, Kamal Awad, Mohamed Elnenny, Esraa Ghanem, Shaimaa El-Jafaary, Ahmed Negida: Meta-Analysis of Creatine for Neuroprotection Against Parkinson’s Disease. CNS & neurological disorders drug targets 02/2017; 16(2)., DOI: 10.2174/1871527315666161104161855

(7) Ebada, Mahmoud Ahmed, Souad Alkanj, Mohamed Ebada, Ahmed H. Abdelkarim, Ahmed Diab, Mohamed Abd Elalem Aziz, Ahmed Magdy Soliman, Notila Fayed, Eshak I. Bahbah, and Ahmed Negida. “Safety and Efficacy of Levetiracetam for the Management of Levodopa-Induced Dyskinesia in Patients with Parkinson’s Disease: A Systematic Review.” CNS & Neurological Disorders-Drug Targets (2019). #Impact Factor: 2.5

(8) Abdelrahman Ibrahim Abushouk, Mostafa Wanees Ahmed El-Husseny, Mayar Magdy, Ammar Ismail, Attia Attia, Hussien Ahmed, Ravikishore Pallanti, Ahmed Negida: Evidence for association between hepatitis C virus and Parkinson’s disease. Neurological Sciences 08/2017; DOI: 10.1007/s10072-017-3077-4

(9) Hussien Ahmed, Abdelrahman Ibrahim Abushouk, Mohamed Gabr, Ahmed Negida, Mohamed M. Abdel-Daim: Parkinson’s disease and pesticides: A meta-analysis of disease connection and genetic alterations. Biomedicine & Pharmacotherapy 06/2017; 90:638-649., DOI: 10.1016/j.biopha.2017.03.100

(10) Ahmed Elgebaly, Mohamed Elfil, Attia Attia, Mayar Magdy, Ahmed Negida: Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson’s disease: a systematic review and meta-analysis. CNS spectrums; 02/2017; 23(1):1-14., DOI: 10.1017/S1092852917000062

(11) Ahmed Negida, Mohamed Elminawy, Gehad El Ashal, Ahmed Essam, Athar Eysa, Mohamed Abd Elalem Aziz: Subthalamic and Pallidal Deep Brain Stimulation for Parkinson’s Disease. Curesus Medical Journal; 02/2018; 10(2)., DOI:10.7759/cureus.2232

Technical Summary of Work:

Parkinson’s disease is the second most common neurodegenerative disorder in the world; until now, there is no cure for Parkinson’s disease. Our research focused on agents, (whether dietary supplements, synthetic drugs, or natural compounds), that might treat Parkinson’s disease.

In 2001, the National Institute of Neurological Disorders and Stroke (NINDS) organized the Committee to Identify Neuroprotective Agents for Parkinson’s (CINAPS) to test a list of potential drugs for neuroprotection against Parkinson’s disease that were tested on several clinical trials through a period for about 15 years. From this list, we identified agents that most likely are not futile (those drugs that showed a statistically significant improvement in at least one clinical trial). This yields the Coenzyme Q10 and the Creatine. We conducted two systematic literature review and meta-analysis of published clinical trials about Coenzyme Q10 and creatine for the neuroprotection against PD. We searched multiple medical electronic databases for all published clinical trials about these drugs. We retrieved the records from the medical electronic databases, and we screened them to select the most relevant clinical trials. The methodology of these clinical trials was assessed for the possible risks of bias according to the Cochrane Risk of Bias assessment tool for randomized controlled trials. Then, data of these clinical trials were extracted and analyzed (pooled together) in a meta-analysis model to give a combined estimate. Results showed that both drugs are not effective in treating Parkinson’s Disease.

We comprehensively searched and screened all medical electronic databases for agents/drugs that have a mechanism of action that opposite the pathological processes of Parkinson’s disease (i.e. antioxidant agents might work against the oxidative stress of Parkinson’s disease). Then, we searched for the other possible molecular mechanisms of action of these drugs as well as their pharmacokinetics, pharmacodynamics, and how they might treat Parkinson’s disease.

For agents that had been already introduced to clinical trial phase, we used qualitative and quantitative evidence synthesis methods to analyze published pre-clinical and clinical data and synthesize evidence about Parkinson’s disease treatments and risk factors. This evidence guides decision making in clinical practice and other researchers to run future clinical trials.

Summary of the Significance of the Work:

This project is important to my field because

There are about 10 million patients with Parkinson’s disease around the world who can not find a cure for their disease. Therefore, there is a continuous search for possible treatments for Parkinson’s disease. Our research is useful to identify candidate treatments that have a potential for treating Parkinson’s and to identify treatments that are not effective.

In 2014, a published systematic review by Cochrane collaboration showed that Coenzyme Q10 is effective in slowing the progress of the disease. Our systematic review provided class 1 evidence that the drug is not effective, therefore, correcting the previous evidence synthesize by the Cochrane review in 2014. As a result, our systematic review was cited in some clinical practice guidelines to indicate that PD patients do not need to buy Coenzyme Q10 because it is not effective in slowing the progress of their disease.

Summary of the Implementation/Influence of the Work

[1] NICE Guidelines of Parkinson’s Disease – July 2017

https://www.nice.org.uk/guidance/ng71/evidence/full-guideline-pdf-4538466253

Our work was cited to provide evidence that Coenzyme Q10 is not effective for treating Parkinson’s disease.

[2] Canadian Guidelines of Parkinson’s Disease – September 2019

** Link: https://www.cmaj.ca/content/cmaj/suppl/2019/09/04/191.36.E989.DC1/Parkinson-final-E-online-LR.pdf

Our work was cited to provide evidence that Coenzyme Q10 is not effective for treating Parkinson’s disease.

[3] The Linus Pauling Institute Micronutrient Information Center at Oregon State University provides scientific information on the health aspects of dietary factors and supplements, food, and beverages for the general public in the United States (https://lpi.oregonstate.edu/). In their guide about the dietary information of Coenzyme Q10, under the section entitled “Parkinson’s disease”, they cited our meta-analysis to highlight that there is no evidence that coenzyme Q10 improved motor-related symptoms or delayed the progression of the Parkinson’s disease when compared to placebo.

** Source: https://lpi.oregonstate.edu/mic/dietary-factors/coenzyme-Q10 (reference no. 68).

[4] 2018 European Society of Cardiology Guidelines for the diagnosis and management of syncope

** Link: https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehy037

Our work was cited to provide evidence that Droxidopa should be used as a treatment for neurogenic orthostatic hypotension (which leads to syncope*).

* Neurogenic Orthostatic Hypotension is a common problem for patients with Parkinson’s disease