Demystify Your Disease’s R&D Readiness

Overview

The development of a therapeutic approach relies on a basic understanding of a disease process and certain research tools, so that researchers can identify targets and begin to develop potential therapies that can affect the disease process. Your group can support the early stages of therapy development by funding the early stages of disease research. Knowing the current understanding of your disease process and development of research tools can help you determine the type of research your group may consider supporting.

Additionally, the therapy development space is a dynamic, innovative field. New approaches and technologies are constantly under investigation. Knowing about these developments and discussing them with your Medical/Scientific Advisory Boards and the medical researchers working on your disease can help you understand whether any of the new technologies can be applied to your disease. However, it is also important to understand whether the approach or technology is ready to be applied to human diseases or is only in the initial stages of development.

Disease Knowledge

Therapies may target the cause (etiology) of the disease. Therapies may also target a protein or other molecule involved in the biological paths that lead to symptoms of the disease (disease pathology). Therefore, it is important to understand what is known about your disease and what information may still be needed to provide an opportunity for a potential target to be chosen.

  • Cause (etiology): One of the prime targets for researchers trying to develop a therapy is the cause of the disease.  At the molecular level, targets for therapies may include a specific gene, RNA, protein, changes in cell processes, and infectious organisms (bacteria, viruses, fungi, etc).  For example, if your disease has a genetic basis:
    • Is the causative gene known? 
    • Is there more than 1 gene involved? 
    • Is the function of the gene clear? 
    • Is it known in which cell types the gene is expressed? 
    • Is the expression of the gene different in different cell types or at different times during a person’s life? 
    • Are all the mutations that cause the disease known and characterized? 
    • Do all mutations causing the gene affect the gene in the same way, such as stopping the gene from being made into a functional protein? 
    • Can specific mutations predict severity of symptoms, age of onset, or progression? 
    • Can different mutations in the same gene cause different diseases? Are there other genes that may be involved in the variability and severity of the symptoms associated with your disease? 
  • Disease process (pathology): Knowing the genetic changes or basic molecular change that can cause a disease does not necessarily mean researchers know how that change manifests in different symptoms and features associated with a disease. In fact, in some cases, the cause may not be well understood or may be a combination of genetic and environmental factors. In either case, the more that is known about the disease process, the more possible targets are available for the development of therapies. For example, if a protein is normally made from the causative gene: 
    • Is the function of the protein made from the gene understood?
    • Does the protein affect the expression of other genes?
    • Is the protein an enzyme in a biological pathway or multiple biological pathways?
    • What biological pathways are disrupted when the level or function of the protein made from the causative gene is changed?
    • Are there other biological processes involved in causing the symptoms and features associated with the disease?
    • Are any of the pathways or biological processes associated with other disease processes?
  • Learn more: The beginning of the video presentation The Ten Things You Need to Pursue Research For Your Disease: What Are the Options for Research and Why is it so Hard? (2015) provides a quick overview of the type of research and research tools that lay the groundwork for  drug development for a rare disease .  The presenter is Brad Margus, who is both a parent of two children with a rare disease and a founder of a nonprofit patient group for that disease. Brad did not start out with a strong background in science and presents his advice for navigating the process of research for rare diseases in an empowering and practical manner. The presentation was taped at a Global Genes Advocacy Summit.

Research Tools

Certain research tools are developed to help scientists understand more about the disease process. Some of these same tools, along with others, are necessary to develop a therapeutic approach, determine whether a potential therapy can move forward to clinical trials, and monitor therapeutic effectiveness throughout clinical trials. It is important to understand which tools have been developed for your disease and which ones may be needed in the future. NCATS Toolkit provides more information and resources about these and other research tools as they relate to preclinical trials in Discovery: Understand Discovery Research Tools

  • Cell lines: Cell lines are developed from a single tissue type and are adapted to grow continuously in the laboratory. The research use of cell lines developed from specific patient populations includes:
    • Isolating the genetic cause of a disease.
    • Understanding gene function.
    • Understanding cellular processes that may be disrupted in the diseased state.
    • Testing drug metabolism and cytotoxicity.
  • Disease models: A disease model is an animal or cell line displaying all or some of the pathological processes that are observed in the actual human disease. For most disease research, having more than 1 disease model is ideal. The research use of disease models includes:
    • Determining in which cell types or tissues a gene is expressed and when.
    • Exploring the function of the gene or its protein. 
    • Understanding the biological processes that lead to symptoms.
    • Studying how the disease develops.
    • Testing potential treatment approaches.
  • Biomarker: Biomarkers are biological molecules found in blood, other body fluids, or tissues that are a sign of a normal or abnormal process or of a condition or disease. 
    • Biomarkers are useful as an indicator of change. Biomarkers may be used to:
      • Diagnose a disease.
      • Determine who is at risk to develop certain symptoms or complications.
      • Track disease progression.
      • Determine how well a person responds to a new medical therapy, including if certain subpopulations within the disease community respond better than others.
      • Serve as an end point of a study.
    • How Biomarkers Can Improve the Drug Development Process is a short slide set from the U.S. Food and Drug Administration (FDA) that provides a quick overview about biomarkers. 
  • Patient information and data: Scientific, clinical, and patient databases can guide even early stages of thearpy development by providing information on multiple members of a disease community.  
    • Collected patient data can help researchers learn more about:
      • Causes and pathology of disease.
      • Clinical picture of a disease.
      • Unmet needs of patients.
      • Preferences of patient population.
    • NCATS Toolkit provides more information about different ways your group can help collect data in Discovery: Determine Patients’ Needs and Prepare for Clinical Trials: Perform Patient Preference Studies and highlights how information from these databases can be used throughout the therapy development process.
    • Rare Diseases Registry Program (RaDaR) was developed by the National Center for Advancing Translational Sciences (NCATS) to provide information tips and resources about the development of patient registries and natural history studies. RaDaR will help you collect data from your patient group that will be useful to thearpy development for your disease and in a way that will allow researchers to use the data.

Genetic Therapies

Gene therapy, CRISPR, and CAR-T cells are several of the promising therapies making headlines in the popular press. These advanced biologics have the potential to treat, and in some cases cure, many types of rare diseases and cancer, but it can be hard to know if any have the possibility to treat your disease. You may wish to gain a basic understanding of these intriguing advances and then discuss their relevance to your disease with your Medical/Scientific Advisory Board and possibly experts in the respective therapy field.

  • Gene therapy is a technique that modifies a person’s genes to treat or cure a disease.
  • Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) or genome editing is considered by the FDA to be a type of gene therapy. 
    • CRISPR–Cas gene editing system is composed of a short strand of RNA, often called guide RNA (gRNA), that is made to target a specific sequence of DNA. The gRNA strand is surrounded by short repeated sequences of RNA that act as scaffolding. The system is linked to an enzyme that is capable of cutting double-stranded DNA.
    • Currently CRISPR is most commonly used to make disease cell and animal models, but is also being explored as to perform rapid diagnosis and to correct disease causing genetic changes.
    • What is Genome Editing? is a short webpage by the the National Human Genome Research Institute (NHGRI) introducing CRISPR and also provides links to more in depth CRISPR topics at the bottom of the page. 
  • Chimeric Antigen Receptor T-Cells (CAR T-Cells) is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells.
    • CAR T-Cells are made by adding a gene for a special receptor that binds to a certain protein on the patient’s cancer cells to the patient’s T cells harvested from their own blood. The special receptor is called a chimeric antigen receptor (CAR).
    • Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion, enabling the a patient’s immune cells to fight their own cancer.
    • CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers is a webpage by the National Cancer Institute that provides an overview of the development of the CAR T-cell therapy as well as its expanding its use.

Finding Disease and Technology Info

Searching for published medical articles, research projects, and clinical trials can help you locate information about the cause of your disease, the biological processes, available animal and cell disease models, and new technologies or therapeutic approaches. Try searching a few key resources, such as: 

  • PubMed is a searchable database of published medical articles maintained by  NIH National Library of Medicine (NLM). Research studies about disease cause and pathology as well as promising novel and innovative approaches and technologies are usually published in medical journals, so you may be able to learn what is known about your disease or a bit more about a new technology by searching PubMed. Although not all of the articles are available for free online, most articles listed in PubMed have a summary (abstract) available.
    • Tips to help you locate articles focused on scientific research: 
      • Use “your disease” (or associated gene or protein if known) as your search term. 
        • Try using the disease term with and without quotation marks.
      • Replace the disease term with any synonyms if you are only finding a limited number of articles. 
      • Add terms such as “gene”, “etiology” (disease cause), “pathology” (disease process) or “treatment” to the main search term or use the advanced search feature to narrow your search results. 
        • You can join any added terms to the disease term or each other using “AND” between the terms. This will limit your search results to articles that contain all the listed terms.
    • Tips to help you understand the impact of a new technology on your disease:
      • Use the technology name or any synonyms as the search term.
        • If you know a disease it is currently being applied to, include the disease name in your search.
        • Many times press releases and even articles in the popular press will note one or more of the publishing researchers names or the actual title of the article, either of which can help in your search. 
      • Scan the published medical article summaries to determine whether the development is currently being:
        • Tested in cell and animal models or humans.
        • Investigated by more than 1 research team.
        • Applied to your disease(s) or a disease that has similar pathological pathways, signs, or symptoms.
        • Reported in a single case report, small study, or in larger studies.
    • If the article is not freely available, the NLM can help you find libraries in your area where you may be able to get the full text. You can search for libraries at National Network of Libraries of Medicine Members Directory. Or you can contact the NLM toll-free at 1-888-346-3656.
    • Alternatively, you can reach out to the contact author of the article and ask if they can provide a full copy to you. To find the contact information on articles found through PubMed, just click on the title in the search list to take you to the summary (abstract) view of the article. The contact information can be found by clicking the “+ expand” next to “Affiliations” just below the list of authors.
    • You can set up email alerts to be notified if new articles are published in a specific search area by simply clicking “Create alert” under the search bar above the listed search results. If you don’t have an account with NLM, the system will walk you through the process. Setting up an account is easy and free.
      • The NIH Library provides a bit more information, including a short video, if you need some help to set up or manage your PubMed alerts: Creating Alerts: PubMed
      • You can choose the frequency you will receive alerts and modify the search in the future.
    • PubMed Help provides answers to frequently asked questions and links to other tips that can help improve your search strategies and locate full text articles if one is not freely available. This resource is frequently updated by NLM.
  • ClinicalTrials.gov was developed by NLM to provide the public with current information on clinical research studies. This resource will only list studies being performed in humans. You can search your disease to determine whether there are any current or past clinical trials or search a new technology to see whether it is or has been studied in clinical trials. Scan the listed clinical trials to determine:
    • Type of clinical trial (treatment or observational).
    • Phase of clinical trial.
    • Number of different centers involved. 
    • Sponsor.
    • Current activity status.
    • Type and number of diseases included in different trials involving the new technique or approach, if you are researching information about a new technology.
  • CenterWatch is a Clinical Trial Listing Service, which provides a list of Institutional Review Board (IRB)-approved clinical trials being conducted internationally. Finding a new technique or approach being used in a clinical trial implies it has advanced to being studied in humans. Likewise finding any study including your disease can help you understand what is known about your disease as well as interested researchers or industry.
  • Research Portfolio Online Reporting Tool (RePORTER) provides access to reports, data, and analyses of research activities at NIH, including the results of NIH-supported research. Although these projects do not usually involve humans, you may want to contact the investigators to learn more about their research, whether it is about your disease or a new technology. This can be a very helpful resource to learn if any cell or animal models are available or being developed for your disease and what aspects of your disease process or cause are being currently researched. To search for studies, enter the name of your disease (or associated gene or protein) or specific technique or approach  in the “Text Search” box and click “Submit Query”.
  • In addition you may wish to reach out to the NIH ICs that focuses on research that either might apply to your disease(s) or a disease that is currently using the technique or approach. 

Keeping Up with Advances

Keeping up with new therapeutic approaches and technologies can be time consuming. However, there are resources that provide summaries and announcements via newsletters or email alerts. Others have webpages that can be checked periodically. 

  • Federal resources: The National Institutes of Health (NIH) and the FDA offer multiple ways to learn about new and emerging developments, including:
    • Free NIH Email Updates, which allow you to choose the news topic areas you would like sent to your email.  Topics under Science include:
      • Basic Research Information.
      • Biomedical Technology Information.
      • Clinical Research Information.
      • Data Science Information.
      • Genetics/Genomics Information.
      • Translational Research Information.
    • News & Events for Human Drugs is an FDA webpage that provides information about new developments.
    • Preclinical Innovation and Core Technologies are NCATS webpages highlighting novel approaches to improve the process of joining basic science discoveries with initial testing of therapies in humans.
      • You can sign up for the monthly NCATS e-newsletter highlighting the latest translational science advances, research news, and upcoming events.
      • NCATS provides a way for subscribers to receive announcements about NCATS’ news releases, funding opportunities, events, program information, and more.
    • Accomplishments in Genomic Medicine is a website with a list of interesting advances in the realm of genomic medicine since 2011 compiled by the National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG).
      • GMWG published a recent paper in the American Journal of Human Genetics based on the notable accomplishments gathered from their list. It can be found at 2019 Genomic Medicine Year in Review.
    • News and Events from National Cancer Institute (NCI)-funded Research and Programs is an NCI webpage highlighting emerging and new approaches and technologies. 
    • Genomics and Precision Health Weekly Update is a Centers for Disease Control and Prevention (CDC) webpage highlighting CDC publications in genomics and precision health.
      • Features the latest information and publications on the public health impact of human genomics and family history, pathogen genomics and advanced molecular detection, machine learning and precision health technologies. 
      • Provides links to specific topics including gene therapy, proteomics, and rare diseases.
      • Sends  email updates (sign up is located in the box on the left side of the page, below the menu).
    • Check the website of the NIH Institutes and Centers (ICs) that includes research areas that may be applicable to your disease(s). Each IC offers options for learning about new developments, whether a webpage, news announcements, or newsletters. 
  • Technology resources:
    • Pharmaceutical Research and Manufacturers of America (PhRMA) has several webpages that highlight new developments in the pharmaceutical industry. Although not directed to patient groups, this is one of the public websites of the industry written in plain language.
      • PhRMA represents some of the country’s leading innovative biopharmaceutical research companies, which are devoted to discovering and developing medicines. This is not a non-profit patient or disease group nor is it affiliated with a government agency.
      • PhRMA: Scientific Discoveries
      • PhRMA: Research and Development
  • Other resources: Large umbrella disease and health organizations as well as innovative public-private partnerships offer webpages with updates, newsletters, webinars, and even in-person conferences that will enable you to learn about new and emerging techniques and developments. Such resources include: 
    • Global Genes is  a nonprofit rare disease group dedicated to connecting, empowering, and inspiring the rare disease community. Many of Global Genes resources and events provide updates on genomics, innovation, and drug development for rare disease research progress, including:
      • Latest News and Rare Daily, which provide links to short articles, interviews, and RareCasts (informative podcasts).
      • Event Hub lists upcoming webinars and conferences.
    • The National Organization for Rare Disorders (NORD) is a nonprofit patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them.  
      • You can Sign Up for Email Updates to learn about NORD events, news, and funding opportunities, including:
        • Medical Updates & Research News.
        • Monthly NORD E-Newsletter.
        • NORD Events.
        • NORD Webinar Series.
      • RareEDU Webinar Archive (2017 to present) is home to the NORD’s live, interactive webinars. Many of the topics of the webinars relate to therapy development including understanding the Orphan Drug Act, several about different aspects of gene therapy, and ways to engage with the FDA. 
    • EveryLife Foundation for Rare Diseases is a nonprofit, nonpartisan organization dedicated to advancing the development of treatment and diagnostic opportunities for rare disease patients through science-driven public policy. The Foundation holds yearly workshops on scientific advances.
      • Rare Disease Scientific Workshop brings together leading stakeholders from industry, academia, patient advocacy organizations and government.
        • Agendas and audiovisual recordings of previous workshops are available.
    • OrphaNews is a freely available, twice-monthly electronic newsletter presenting an overview of scientific and political news about rare diseases and orphan drugs. 
      • Produced by OrphaNet, the European information and resources database for rare and genetic diseases.
      • You can Subscribe to have the newsletter delivered to your email.
      • You can also read the latest or past editions directly on the website.

Tips for Success

  • Scientists performing research to understand a disease process may be associated with the government, a university (academic institutions), a non-profit organization,or pharmaceutical industry.
  • If you don’t have anyone with a scientific background in your group as staff or volunteers, consider hiring a graduate student, medical student, postdoc, or fellow who can do the literature search for you and report what they found in an understandable format. 
  • Consult with your Scientific/Medical Advisory Board about which research or research tools may still be needed. Remember, not everything has to be known before the search for new treatments or a cure begins. 
  • Developing more than 1 disease model may be necessary and optimal. Again, relying on your scientific and medical advisory board to evaluate this need rather than a researcher asking to be funded to do the research is important.
  • Not all emerging therapeutic approaches or technologies will be applicable to your disease and popular press may exaggerate the readiness of a new development. Therefore you may want to review any new developments with your Scientific/Medical Advisory Board or talk to the leading medical researchers working on your disease(s).

Resources

Disease Knowledge
Research Tools
How Biomarkers Can Improve the Drug Development Process U.S. Food and Drug Administration (FDA) (link)
Rare Diseases Registry Program (RaDaR) National Center for Advancing Translational Sciences (NCATS) (link)
Genetic Therapies
What is Gene Therapy? U.S. Food and Drug Administration (FDA) (link)
Gene Therapy Yesterday, Today and Tomorrow National Organization for Rare Disorders (NORD) (link)
The Science Behind Gene Therapy National Organization for Rare Disorders (NORD) (link)
The FDA's Role in Gene Therapy National Organization for Rare Disorders (NORD) (link)
Understanding the Gene Therapy Process and Aftercare National Organization for Rare Disorders (NORD) (link)
Life After Gene Therapy National Organization for Rare Disorders (NORD) (link)
What is genome editing? National Human Genome Research Institute (NHGRI) (link)
Finding Disease and Technology Info
PubMed National Library of Medicine (NLM) (link)
ClinicalTrials.gov National Library of Medicine (NLM) (link)
Institutional Review Boards Frequently Asked Questions U.S. Food and Drug Administration (FDA) (link)
Research Portfolio Online Reporting Tool (RePORTER) National Institutes of Health (NIH) (link)
List of NIH Institutes, Centers, and Offices National Institutes of Health (NIH) (link)
Keeping Up with Advances
Free NIH Email Updates National Institutes of Health (NIH) (link)
News & Events for Human Drugs U.S. Food and Drug Administration (FDA) (link)
Preclinical Innovation National Center of Advancing Translational Sciences (NCATS) (link)
Core Technologies National Center of Advancing Translational Sciences (NCATS) (link)
Monthly NCATS e-newsletter National Center of Advancing Translational Sciences (NCATS) (link)
Receive NCATS Announcements National Center of Advancing Translational Sciences (NCATS) (link)
Accomplishments in Genomic Medicine National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG) (link)
2019 Genomic Medicine Year in Review National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG) (link)
Genomics and Precision Health Weekly Update Centers for Disease Control and Prevention (CDC) (link)
PhRMA: Scientific Discoveries Pharmaceutical Research and Manufacturers of America (PhRMA) (link)
PhRMA: Research and Development Pharmaceutical Research and Manufacturers of America (PhRMA) (link)
Sign Up for NORD Email Updates National Organization for Rare Disorders (NORD) (link)
Rare Disease Scientific Workshop EveryLife Foundation for Rare Diseases (link)
OrphaNews Orphanet (link)

The development of a therapeutic approach relies on a basic understanding of a disease process and certain research tools, so that researchers can identify targets and begin to develop potential therapies that can affect the disease process. Your group can support the early stages of therapy development by funding the early stages of disease research. Knowing the current understanding of your disease process and development of research tools can help you determine the type of research your group may consider supporting.

Additionally, the therapy development space is a dynamic, innovative field. New approaches and technologies are constantly under investigation. Knowing about these developments and discussing them with your Medical/Scientific Advisory Boards and the medical researchers working on your disease can help you understand whether any of the new technologies can be applied to your disease. However, it is also important to understand whether the approach or technology is ready to be applied to human diseases or is only in the initial stages of development.

Therapies may target the cause (etiology) of the disease. Therapies may also target a protein or other molecule involved in the biological paths that lead to symptoms of the disease (disease pathology). Therefore, it is important to understand what is known about your disease and what information may still be needed to provide an opportunity for a potential target to be chosen.

  • Cause (etiology): One of the prime targets for researchers trying to develop a therapy is the cause of the disease.  At the molecular level, targets for therapies may include a specific gene, RNA, protein, changes in cell processes, and infectious organisms (bacteria, viruses, fungi, etc).  For example, if your disease has a genetic basis:
    • Is the causative gene known? 
    • Is there more than 1 gene involved? 
    • Is the function of the gene clear? 
    • Is it known in which cell types the gene is expressed? 
    • Is the expression of the gene different in different cell types or at different times during a person’s life? 
    • Are all the mutations that cause the disease known and characterized? 
    • Do all mutations causing the gene affect the gene in the same way, such as stopping the gene from being made into a functional protein? 
    • Can specific mutations predict severity of symptoms, age of onset, or progression? 
    • Can different mutations in the same gene cause different diseases? Are there other genes that may be involved in the variability and severity of the symptoms associated with your disease? 
  • Disease process (pathology): Knowing the genetic changes or basic molecular change that can cause a disease does not necessarily mean researchers know how that change manifests in different symptoms and features associated with a disease. In fact, in some cases, the cause may not be well understood or may be a combination of genetic and environmental factors. In either case, the more that is known about the disease process, the more possible targets are available for the development of therapies. For example, if a protein is normally made from the causative gene: 
    • Is the function of the protein made from the gene understood?
    • Does the protein affect the expression of other genes?
    • Is the protein an enzyme in a biological pathway or multiple biological pathways?
    • What biological pathways are disrupted when the level or function of the protein made from the causative gene is changed?
    • Are there other biological processes involved in causing the symptoms and features associated with the disease?
    • Are any of the pathways or biological processes associated with other disease processes?
  • Learn more: The beginning of the video presentation The Ten Things You Need to Pursue Research For Your Disease: What Are the Options for Research and Why is it so Hard? (2015) provides a quick overview of the type of research and research tools that lay the groundwork for  drug development for a rare disease .  The presenter is Brad Margus, who is both a parent of two children with a rare disease and a founder of a nonprofit patient group for that disease. Brad did not start out with a strong background in science and presents his advice for navigating the process of research for rare diseases in an empowering and practical manner. The presentation was taped at a Global Genes Advocacy Summit.

Certain research tools are developed to help scientists understand more about the disease process. Some of these same tools, along with others, are necessary to develop a therapeutic approach, determine whether a potential therapy can move forward to clinical trials, and monitor therapeutic effectiveness throughout clinical trials. It is important to understand which tools have been developed for your disease and which ones may be needed in the future. NCATS Toolkit provides more information and resources about these and other research tools as they relate to preclinical trials in Discovery: Understand Discovery Research Tools

  • Cell lines: Cell lines are developed from a single tissue type and are adapted to grow continuously in the laboratory. The research use of cell lines developed from specific patient populations includes:
    • Isolating the genetic cause of a disease.
    • Understanding gene function.
    • Understanding cellular processes that may be disrupted in the diseased state.
    • Testing drug metabolism and cytotoxicity.
  • Disease models: A disease model is an animal or cell line displaying all or some of the pathological processes that are observed in the actual human disease. For most disease research, having more than 1 disease model is ideal. The research use of disease models includes:
    • Determining in which cell types or tissues a gene is expressed and when.
    • Exploring the function of the gene or its protein. 
    • Understanding the biological processes that lead to symptoms.
    • Studying how the disease develops.
    • Testing potential treatment approaches.
  • Biomarker: Biomarkers are biological molecules found in blood, other body fluids, or tissues that are a sign of a normal or abnormal process or of a condition or disease. 
    • Biomarkers are useful as an indicator of change. Biomarkers may be used to:
      • Diagnose a disease.
      • Determine who is at risk to develop certain symptoms or complications.
      • Track disease progression.
      • Determine how well a person responds to a new medical therapy, including if certain subpopulations within the disease community respond better than others.
      • Serve as an end point of a study.
    • How Biomarkers Can Improve the Drug Development Process is a short slide set from the U.S. Food and Drug Administration (FDA) that provides a quick overview about biomarkers. 
  • Patient information and data: Scientific, clinical, and patient databases can guide even early stages of thearpy development by providing information on multiple members of a disease community.  
    • Collected patient data can help researchers learn more about:
      • Causes and pathology of disease.
      • Clinical picture of a disease.
      • Unmet needs of patients.
      • Preferences of patient population.
    • NCATS Toolkit provides more information about different ways your group can help collect data in Discovery: Determine Patients’ Needs and Prepare for Clinical Trials: Perform Patient Preference Studies and highlights how information from these databases can be used throughout the therapy development process.
    • Rare Diseases Registry Program (RaDaR) was developed by the National Center for Advancing Translational Sciences (NCATS) to provide information tips and resources about the development of patient registries and natural history studies. RaDaR will help you collect data from your patient group that will be useful to thearpy development for your disease and in a way that will allow researchers to use the data.

Gene therapy, CRISPR, and CAR-T cells are several of the promising therapies making headlines in the popular press. These advanced biologics have the potential to treat, and in some cases cure, many types of rare diseases and cancer, but it can be hard to know if any have the possibility to treat your disease. You may wish to gain a basic understanding of these intriguing advances and then discuss their relevance to your disease with your Medical/Scientific Advisory Board and possibly experts in the respective therapy field.

  • Gene therapy is a technique that modifies a person’s genes to treat or cure a disease.
  • Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) or genome editing is considered by the FDA to be a type of gene therapy. 
    • CRISPR–Cas gene editing system is composed of a short strand of RNA, often called guide RNA (gRNA), that is made to target a specific sequence of DNA. The gRNA strand is surrounded by short repeated sequences of RNA that act as scaffolding. The system is linked to an enzyme that is capable of cutting double-stranded DNA.
    • Currently CRISPR is most commonly used to make disease cell and animal models, but is also being explored as to perform rapid diagnosis and to correct disease causing genetic changes.
    • What is Genome Editing? is a short webpage by the the National Human Genome Research Institute (NHGRI) introducing CRISPR and also provides links to more in depth CRISPR topics at the bottom of the page. 
  • Chimeric Antigen Receptor T-Cells (CAR T-Cells) is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells.
    • CAR T-Cells are made by adding a gene for a special receptor that binds to a certain protein on the patient’s cancer cells to the patient’s T cells harvested from their own blood. The special receptor is called a chimeric antigen receptor (CAR).
    • Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion, enabling the a patient’s immune cells to fight their own cancer.
    • CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers is a webpage by the National Cancer Institute that provides an overview of the development of the CAR T-cell therapy as well as its expanding its use.

Searching for published medical articles, research projects, and clinical trials can help you locate information about the cause of your disease, the biological processes, available animal and cell disease models, and new technologies or therapeutic approaches. Try searching a few key resources, such as: 

  • PubMed is a searchable database of published medical articles maintained by  NIH National Library of Medicine (NLM). Research studies about disease cause and pathology as well as promising novel and innovative approaches and technologies are usually published in medical journals, so you may be able to learn what is known about your disease or a bit more about a new technology by searching PubMed. Although not all of the articles are available for free online, most articles listed in PubMed have a summary (abstract) available.
    • Tips to help you locate articles focused on scientific research: 
      • Use “your disease” (or associated gene or protein if known) as your search term. 
        • Try using the disease term with and without quotation marks.
      • Replace the disease term with any synonyms if you are only finding a limited number of articles. 
      • Add terms such as “gene”, “etiology” (disease cause), “pathology” (disease process) or “treatment” to the main search term or use the advanced search feature to narrow your search results. 
        • You can join any added terms to the disease term or each other using “AND” between the terms. This will limit your search results to articles that contain all the listed terms.
    • Tips to help you understand the impact of a new technology on your disease:
      • Use the technology name or any synonyms as the search term.
        • If you know a disease it is currently being applied to, include the disease name in your search.
        • Many times press releases and even articles in the popular press will note one or more of the publishing researchers names or the actual title of the article, either of which can help in your search. 
      • Scan the published medical article summaries to determine whether the development is currently being:
        • Tested in cell and animal models or humans.
        • Investigated by more than 1 research team.
        • Applied to your disease(s) or a disease that has similar pathological pathways, signs, or symptoms.
        • Reported in a single case report, small study, or in larger studies.
    • If the article is not freely available, the NLM can help you find libraries in your area where you may be able to get the full text. You can search for libraries at National Network of Libraries of Medicine Members Directory. Or you can contact the NLM toll-free at 1-888-346-3656.
    • Alternatively, you can reach out to the contact author of the article and ask if they can provide a full copy to you. To find the contact information on articles found through PubMed, just click on the title in the search list to take you to the summary (abstract) view of the article. The contact information can be found by clicking the “+ expand” next to “Affiliations” just below the list of authors.
    • You can set up email alerts to be notified if new articles are published in a specific search area by simply clicking “Create alert” under the search bar above the listed search results. If you don’t have an account with NLM, the system will walk you through the process. Setting up an account is easy and free.
      • The NIH Library provides a bit more information, including a short video, if you need some help to set up or manage your PubMed alerts: Creating Alerts: PubMed
      • You can choose the frequency you will receive alerts and modify the search in the future.
    • PubMed Help provides answers to frequently asked questions and links to other tips that can help improve your search strategies and locate full text articles if one is not freely available. This resource is frequently updated by NLM.
  • ClinicalTrials.gov was developed by NLM to provide the public with current information on clinical research studies. This resource will only list studies being performed in humans. You can search your disease to determine whether there are any current or past clinical trials or search a new technology to see whether it is or has been studied in clinical trials. Scan the listed clinical trials to determine:
    • Type of clinical trial (treatment or observational).
    • Phase of clinical trial.
    • Number of different centers involved. 
    • Sponsor.
    • Current activity status.
    • Type and number of diseases included in different trials involving the new technique or approach, if you are researching information about a new technology.
  • CenterWatch is a Clinical Trial Listing Service, which provides a list of Institutional Review Board (IRB)-approved clinical trials being conducted internationally. Finding a new technique or approach being used in a clinical trial implies it has advanced to being studied in humans. Likewise finding any study including your disease can help you understand what is known about your disease as well as interested researchers or industry.
  • Research Portfolio Online Reporting Tool (RePORTER) provides access to reports, data, and analyses of research activities at NIH, including the results of NIH-supported research. Although these projects do not usually involve humans, you may want to contact the investigators to learn more about their research, whether it is about your disease or a new technology. This can be a very helpful resource to learn if any cell or animal models are available or being developed for your disease and what aspects of your disease process or cause are being currently researched. To search for studies, enter the name of your disease (or associated gene or protein) or specific technique or approach  in the “Text Search” box and click “Submit Query”.
  • In addition you may wish to reach out to the NIH ICs that focuses on research that either might apply to your disease(s) or a disease that is currently using the technique or approach. 

Keeping up with new therapeutic approaches and technologies can be time consuming. However, there are resources that provide summaries and announcements via newsletters or email alerts. Others have webpages that can be checked periodically. 

  • Federal resources: The National Institutes of Health (NIH) and the FDA offer multiple ways to learn about new and emerging developments, including:
    • Free NIH Email Updates, which allow you to choose the news topic areas you would like sent to your email.  Topics under Science include:
      • Basic Research Information.
      • Biomedical Technology Information.
      • Clinical Research Information.
      • Data Science Information.
      • Genetics/Genomics Information.
      • Translational Research Information.
    • News & Events for Human Drugs is an FDA webpage that provides information about new developments.
    • Preclinical Innovation and Core Technologies are NCATS webpages highlighting novel approaches to improve the process of joining basic science discoveries with initial testing of therapies in humans.
      • You can sign up for the monthly NCATS e-newsletter highlighting the latest translational science advances, research news, and upcoming events.
      • NCATS provides a way for subscribers to receive announcements about NCATS’ news releases, funding opportunities, events, program information, and more.
    • Accomplishments in Genomic Medicine is a website with a list of interesting advances in the realm of genomic medicine since 2011 compiled by the National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG).
      • GMWG published a recent paper in the American Journal of Human Genetics based on the notable accomplishments gathered from their list. It can be found at 2019 Genomic Medicine Year in Review.
    • News and Events from National Cancer Institute (NCI)-funded Research and Programs is an NCI webpage highlighting emerging and new approaches and technologies. 
    • Genomics and Precision Health Weekly Update is a Centers for Disease Control and Prevention (CDC) webpage highlighting CDC publications in genomics and precision health.
      • Features the latest information and publications on the public health impact of human genomics and family history, pathogen genomics and advanced molecular detection, machine learning and precision health technologies. 
      • Provides links to specific topics including gene therapy, proteomics, and rare diseases.
      • Sends  email updates (sign up is located in the box on the left side of the page, below the menu).
    • Check the website of the NIH Institutes and Centers (ICs) that includes research areas that may be applicable to your disease(s). Each IC offers options for learning about new developments, whether a webpage, news announcements, or newsletters. 
  • Technology resources:
    • Pharmaceutical Research and Manufacturers of America (PhRMA) has several webpages that highlight new developments in the pharmaceutical industry. Although not directed to patient groups, this is one of the public websites of the industry written in plain language.
      • PhRMA represents some of the country’s leading innovative biopharmaceutical research companies, which are devoted to discovering and developing medicines. This is not a non-profit patient or disease group nor is it affiliated with a government agency.
      • PhRMA: Scientific Discoveries
      • PhRMA: Research and Development
  • Other resources: Large umbrella disease and health organizations as well as innovative public-private partnerships offer webpages with updates, newsletters, webinars, and even in-person conferences that will enable you to learn about new and emerging techniques and developments. Such resources include: 
    • Global Genes is  a nonprofit rare disease group dedicated to connecting, empowering, and inspiring the rare disease community. Many of Global Genes resources and events provide updates on genomics, innovation, and drug development for rare disease research progress, including:
      • Latest News and Rare Daily, which provide links to short articles, interviews, and RareCasts (informative podcasts).
      • Event Hub lists upcoming webinars and conferences.
    • The National Organization for Rare Disorders (NORD) is a nonprofit patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them.  
      • You can Sign Up for Email Updates to learn about NORD events, news, and funding opportunities, including:
        • Medical Updates & Research News.
        • Monthly NORD E-Newsletter.
        • NORD Events.
        • NORD Webinar Series.
      • RareEDU Webinar Archive (2017 to present) is home to the NORD’s live, interactive webinars. Many of the topics of the webinars relate to therapy development including understanding the Orphan Drug Act, several about different aspects of gene therapy, and ways to engage with the FDA. 
    • EveryLife Foundation for Rare Diseases is a nonprofit, nonpartisan organization dedicated to advancing the development of treatment and diagnostic opportunities for rare disease patients through science-driven public policy. The Foundation holds yearly workshops on scientific advances.
      • Rare Disease Scientific Workshop brings together leading stakeholders from industry, academia, patient advocacy organizations and government.
        • Agendas and audiovisual recordings of previous workshops are available.
    • OrphaNews is a freely available, twice-monthly electronic newsletter presenting an overview of scientific and political news about rare diseases and orphan drugs. 
      • Produced by OrphaNet, the European information and resources database for rare and genetic diseases.
      • You can Subscribe to have the newsletter delivered to your email.
      • You can also read the latest or past editions directly on the website.
  • Scientists performing research to understand a disease process may be associated with the government, a university (academic institutions), a non-profit organization,or pharmaceutical industry.
  • If you don’t have anyone with a scientific background in your group as staff or volunteers, consider hiring a graduate student, medical student, postdoc, or fellow who can do the literature search for you and report what they found in an understandable format. 
  • Consult with your Scientific/Medical Advisory Board about which research or research tools may still be needed. Remember, not everything has to be known before the search for new treatments or a cure begins. 
  • Developing more than 1 disease model may be necessary and optimal. Again, relying on your scientific and medical advisory board to evaluate this need rather than a researcher asking to be funded to do the research is important.
  • Not all emerging therapeutic approaches or technologies will be applicable to your disease and popular press may exaggerate the readiness of a new development. Therefore you may want to review any new developments with your Scientific/Medical Advisory Board or talk to the leading medical researchers working on your disease(s).

Resources

Disease Knowledge
Research Tools
How Biomarkers Can Improve the Drug Development Process U.S. Food and Drug Administration (FDA) (link)
Rare Diseases Registry Program (RaDaR) National Center for Advancing Translational Sciences (NCATS) (link)
Genetic Therapies
What is Gene Therapy? U.S. Food and Drug Administration (FDA) (link)
Gene Therapy Yesterday, Today and Tomorrow National Organization for Rare Disorders (NORD) (link)
The Science Behind Gene Therapy National Organization for Rare Disorders (NORD) (link)
The FDA's Role in Gene Therapy National Organization for Rare Disorders (NORD) (link)
Understanding the Gene Therapy Process and Aftercare National Organization for Rare Disorders (NORD) (link)
Life After Gene Therapy National Organization for Rare Disorders (NORD) (link)
What is genome editing? National Human Genome Research Institute (NHGRI) (link)
Finding Disease and Technology Info
PubMed National Library of Medicine (NLM) (link)
ClinicalTrials.gov National Library of Medicine (NLM) (link)
Institutional Review Boards Frequently Asked Questions U.S. Food and Drug Administration (FDA) (link)
Research Portfolio Online Reporting Tool (RePORTER) National Institutes of Health (NIH) (link)
List of NIH Institutes, Centers, and Offices National Institutes of Health (NIH) (link)
Keeping Up with Advances
Free NIH Email Updates National Institutes of Health (NIH) (link)
News & Events for Human Drugs U.S. Food and Drug Administration (FDA) (link)
Preclinical Innovation National Center of Advancing Translational Sciences (NCATS) (link)
Core Technologies National Center of Advancing Translational Sciences (NCATS) (link)
Monthly NCATS e-newsletter National Center of Advancing Translational Sciences (NCATS) (link)
Receive NCATS Announcements National Center of Advancing Translational Sciences (NCATS) (link)
Accomplishments in Genomic Medicine National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG) (link)
2019 Genomic Medicine Year in Review National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG) (link)
Genomics and Precision Health Weekly Update Centers for Disease Control and Prevention (CDC) (link)
PhRMA: Scientific Discoveries Pharmaceutical Research and Manufacturers of America (PhRMA) (link)
PhRMA: Research and Development Pharmaceutical Research and Manufacturers of America (PhRMA) (link)
Sign Up for NORD Email Updates National Organization for Rare Disorders (NORD) (link)
Rare Disease Scientific Workshop EveryLife Foundation for Rare Diseases (link)
OrphaNews Orphanet (link)