MORPH

Short Title of Project

MEMORI-AD

Project Title

Monitoring drug Efficacy through Multi-Omics Research Initiative in Alzheimer’s Disease
(MEMORI-AD)

Summary

In the Philippines, it is estimated that 10.6% of Filipinos aged 60 years and above have dementia, with 85.5% eventually being diagnosed as Alzheimer’s disease (AD) (Dominguez et al., 2018). This indicates a pressing need to address neurodegenerative diseases and other non-communicable diseases in the country. Recommended drugs have been established for dementia - some being acetylcholinesterase inhibitors like rivastigmine, donepezil and galantamine as monotherapy or combined with memantine for moderate and severe AD (Farlow and Cummings 2007).

There is currently no available study demonstrating the clinical effects of recommended drugs for AD in the Filipino population. Hence, neither drug response nor adverse effects of Filipino AD patients are known. In addition, while the gut-brain axis relationship is well established, there is paucity of data on this from current clinical studies in the local setting. Knowing which drugs are effective for Filipinos and which are associated with less adverse events are essential to maximize cost-effectivity and improve the quality of life of patients. Knowing how drug intake affects gut flora, and how flora affects AD or drug response are also essential in the application of modern knowledge in neurology: the gut-brain axis and how they affect each other, and especially how such interactions are observed in Filipino AD patients. This can help us understand how gut flora affects cognition, and may open additional avenues for drug discovery in the future.

With the recently enacted Mental Health Act (RA 11036), these information are of importance to develop locally-relevant clinical management for Filipinos afflicted with AD. In this descriptive, prospective cohort study, drug response of Filipino patients newly diagnosed with AD will be investigated employing innovative multiOMICs technology to characterize genetic variations via whole exome sequencing, gut microbiota profile by shotgun metagenomic sequencing, and metabolome profile by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Through collaboration between the basic (Molecular Biology and Medical Microbiology) and clinical sciences (Adult Neurology), this study will provide evidence for the consideration of interested local medical societies primarily managing patients with AD. This project also provides an avenue for the training of clinical neurologists and young translational researchers particularly the MD-PhD in Molecular Medicine students in the conduct of precision medicine research in neurosciences to improve patient management.

Cited literature

• Dominguez, J., de Guzman, MF., Macario Jr, R., Phung, T., & Kieu T. (2018). Prevalence of dementia and associated risk factors: a population-based study in the Philippines. Journal of Alzheimer’s Disease, 63 (3): 1065-1073. doi: 10.3233/JAD-180095
• Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer's disease. Am J Med. 2007 May;120(5):388-97. doi: 10.1016/j.amjmed.2006.08.036. PMID: 17466645.

Graphical Abstract

Among a cohort of Filipinos diagnosed with late onset AD, the current study will investigate the clinical, genetic, gut microbiota and gut metabolic factors, which are recognized contributory factors to an individual’s drug response or non-response status. All these are directed to maximize drug effectiveness and improve quality of life of Filipino patients with AD.

Study Period

January 1, 2022 to December 31, 2024

Collaborators

1. The Medical City
2. Cardinal Santos Medical Center
3. Philippine Genome Center

Team Members

Contact Us

Fresthel Monica M. Climacosa, MD, PhD
Program Leader
fmclimacosa@up.edu.ph

Project Title

Molecular Epidemiology of Mycobacterium tuberculosis and Human Immunodeficiency Virus and Immunophenotyping of Adult Filipino TB/HIV Co-infected Patients

Summary

This cross-sectional prospective molecular epidemiologic study aims to determine the existing and predominant genotypes or strains of Mycobacterium tuberculosis and HIV in the adult Filipino TB/HIV co-infected patient population. It also aims to determine the prevalence of drug-resistant TB and HIV and genetic mutations associated with resistance to anti-TB and antiretroviral drugs. Findings from these can add to our understanding of the transmission dynamics of TB and HIV, which in turn, can aid in developing or improving strategies for effective prevention and control of these overlapping infectious diseases. This study also incorporates immunophenotyping to determine host immune markers in TB/HIV co-infected patients in the country.<

The project targets to recruit 85 TB/HIV co-infected patients from the Philippine General Hospital. This is the first study in the Philippines that will use whole genome sequencing for genotyping and mutation profiling of M. tuberculosis and HIV isolates, as well as immunophenotyping, in adult Filipino TB/HIV co-infected patients.<

Graphical Abstract

Study Period

January 1, 2022 to December 31, 2024

Collaborators

1. College of Medicine, University of the Philippines Manila
2. College of Public Health, University of the Philippines Manila
3. Center for Informatics, University of San Agustin, Iloilo
4. San Lazaro Hospital

Team Members

Contact Us

John Carlo Malabad, MD, PhD
Co-Investigator
jmmalabad@up.edu.ph

Project Title

Determinants of acquisition, persistence, and clearance of oncogenic cervical human papillomavirus infection in a cohort of women in rural and urban Philippines using a multi-OMICS approach (DEFEAT HPV)

Summary

Human papillomavirus (HPV) infection is one of the most studied risk factors for cervical cancer, the second most common cause of cancer-related death among Filipino women. However, population-based epidemiological data on cervical HPV in most parts of the Philippines remains unknown. In addition, local reports on co-infections with other lower genital tract pathogens, which are commonly reported globally, are lacking.

DEFEAT HPV aims to determine the molecular epidemiology and natural history of HPV infection among reproductive-aged Filipino women using a community-based prospective cohort design. Cervicovaginal swabs will be collected from all screened participants coming from both urban and rural sites. For positive swabs, the HPV genotypes will be determined. To determine HPV clearance, persistence, and/or acquisition, a subset of cases and controls will be followed up after 6 and 12 months for repeat HPV screening. Metagenomic and metabolomic analysis of the cervicovaginal swabs will also be done at baseline and after 6 months.

Determining the HPV genotype and distribution among the general population can help in addressing the gap in the knowledge of the epidemiology of HPV in the Philippines. The molecular epidemiology of HPV genotype distribution is essential to estimate the potential impact of prophylactic HPV vaccination, and to assess the importance of HPV testing-based cervical screening. DEFEAT HPV will update the prevalence and genotypic distribution of HPV infection among Filipino women of reproductive age, which can determine whether available vaccines in the HPV vaccination program in the Philippines captures the most prevalent high-risk HPV genotypes in the country. In addition, this study will also identify cervicovaginal community state types and bacterial taxa associated with different infection statuses of HPV. This can be used in developing a biomarker that can help predict the risk of developing persistent HPV infection and cervical cancer in Filipino women.

Graphical Abstract

Study Period

January 1, 2022 to December 31, 2024

Collaborators

1. Likhaan Center for Women’s Health, Inc.
2. Nagasaki University School of Tropical Medicine and Global Health

Team Members

Contact Us

Sheriah Laine M. de Paz-Silava, MD, PhD
Project Leader
smdepaz@up.edu.ph

Project Title

Identification of Biomarkers to Distinguish Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma

Summary

Among well-differentiated thyroid neoplasms, follicular thyroid neoplasms comprise a diagnostic dilemma. This is due to the difficulty of distinguishing between benign and malignant neoplasms on histologic assessment. The goal of this project is to identify gene targets which can differentiate between a malignant and benign follicular neoplasm by comparing the gene expression of candidate genes and its association with clinical outcomes. Gene targets which prove to be significantly differentially expressed following quantitative PCR (qPCR) will be further correlated with clinical features such as tumor size, metastasis and other clinical parameters to establish clinical relevance. Additionally, genomic profiles comparing mutational distribution of known cancer genes between FTA and FTC will also be described to further characterize the differences between follicular neoplasms. These target genes can be a basis for development of a gene panel or classifiers to decrease the instances of diagnostic dilemma in FTC and FTA, thus limiting unnecessary treatment and improving the care of Filipino patients.

Graphical Abstract

Study Period

January 1, 2023 to December 31, 2024

Collaborators

1. University of the Philippines College of Medicine
2. Department of Laboratories, University of the Philippines - Philippine General Hospital

Team Members

Contact Us

Cecile C. Dungog, MD, PhD
Project Leader
ccdungog@up.edu.ph