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Module

MMB8036 : Therapy Development for Rare Diseases: the neuromuscular paradigm

  • Offered for Year: 2020/21
  • Module Leader(s): Dr Michela Guglieri
  • Lecturer: Dr Alison Blain, Professor Volker Straub, Mr Jan Deckers, Miss Liz Greally, Dr Anna Mayhew, Ms Becca Leary
  • Visiting Lecturer: Dr Anna Sarkozy
  • Owning School: FMS Graduate School
  • Teaching Location: Newcastle City Campus
Semesters
Semester 1 Credit Value: 20
ECTS Credits: 10.0

Aims

This module will provide key background information on normal muscle physiology and neuromuscular structure and function. It will continue into detailed discussion of the neuromuscular diseases, and the impact that these rare conditions have on muscle structure and function. The challenges and promise of novel therapeutic strategies for neuromuscular diseases, including gene and cell-based approached, will be a key focus of the module, which emphasises the 'bench to bedside' approach of translating laboratory findings into therapeutic interventions. Specific aims will be:
1. To educate students in the development of therapy for rare diseases, using neuromuscular diseases as an example of a growing field of research.
2. To explore the challenges and promise of genetic modifying therapies and gene therapy.
3. To develop students' understanding of the role of cellular and animal models in moving therapies into practice and the design of preclinical experiments.
4. To explore the challenges in drug development and clinical trial designs in rare diseases and how these can be addressed.
5. To introduce the students to ethical issues related to drug development and national and international regulatory requirements.

Outline Of Syllabus

The module will start with an introduction to neuromuscular diseases as an example of rare diseases. This will include normal muscle structure and function, including normal muscle physiology, how neuromuscular diseases impact on this and the clinical and electrophysiological manifestations of muscle dysfunction across the neuromuscular system. The module will then go on to cover:
1. How to define the target for clinical research: identify the molecular pathology of neuromuscular diseases to understand heterogeneity and identify potential therapeutic targets.
2. Model systems to study diseases: uses and limitations of cell cultures, zebra fish, mouse and other animal models to understand disease pathology and test therapeutic approaches. This includes an overview of existing models, methodology to develop new models and a critical appraisal of claims of therapeutic success in the preclinical setting.
3. Drug development in rare diseases: the different phases of clinical trials; discussion on clinical trial designs, clinical and biochemical outcome measures, their current use and future applications with examples from current pre-clinical studies and clinical trials.
4. The state of the art novel therapeutic strategies for neuromuscular diseases including: gene and cell based therapies; understanding the targets and use of biomarkers; genetic therapy for neuromuscular diseases applications of antisense oligonucleotide technology in neuromuscular diseases; other targets for therapy development including downstream targets and protein up regulation; pros and cons of clinical research on repurposing drugs.
5. Regulatory requirements and ethical issues in drug development for rare diseases.
6. The importance of international collaborations and examples of global networks and infrastructures to facilitate clinical research.
During the module, students will have the opportunity to meet patients with different neuromuscular diseases and will also have the opportunity to learn to critically assess preclinical research. This will be in the form of a session during which students will be provided with a fictional application from a company planning a clinical trial in a specified neuromuscular disease. Students will be encouraged to identify and discuss the strengths and limitations of the application.

Teaching Methods

Please note that module leaders are reviewing the module teaching and assessment methods for Semester 2 modules, in light of the Covid-19 restrictions. There may also be a few further changes to Semester 1 modules. Final information will be available by the end of August 2020 in for Semester 1 modules and the end of October 2020 for Semester 2 modules.

Teaching Activities
Category Activity Number Length Student Hours Comment
Guided Independent StudyAssessment preparation and completion132:0032:00Preparation for group exercise
Structured Guided LearningLecture materials81:008:00non-synchronous online
Scheduled Learning And Teaching ActivitiesPractical11:001:00Present in person: Mock sessions on study designs.
Scheduled Learning And Teaching ActivitiesSmall group teaching71:007:00Synchronous online:Seminars
Scheduled Learning And Teaching ActivitiesSmall group teaching24:008:00Synchronous online: Experimental design/ critical analysis of literature as prep for presentations
Scheduled Learning And Teaching ActivitiesSmall group teaching12:002:00Synchronous online:Ethical debates and problems in rare disease translational research
Scheduled Learning And Teaching ActivitiesWorkshops50:201:40Synchronous online: Intro/assignment of project topics/Q&A sessions
Scheduled Learning And Teaching ActivitiesWorkshops11:001:00Synchronous online: Meet the patients session
Scheduled Learning And Teaching ActivitiesWorkshops23:006:00Present in person: Assessed oral presentation sessions I and II
Guided Independent StudyIndependent study1133:20133:20N/A
Total200:00
Teaching Rationale And Relationship

The series of lecture materials and seminars will deliver the key information to meet knowledge outcomes, and guided reading will reinforce and develop this knowledge. Small group teaching sessions allow for interactive discussion and preparation around data analysis and experimental design. The practical session delivers a session to critically assess a mock example of preclinical research.

Assessment Methods

Please note that module leaders are reviewing the module teaching and assessment methods for Semester 2 modules, in light of the Covid-19 restrictions. There may also be a few further changes to Semester 1 modules. Final information will be available by the end of August 2020 in for Semester 1 modules and the end of October 2020 for Semester 2 modules.

The format of resits will be determined by the Board of Examiners

Exams
Description Length Semester When Set Percentage Comment
Written Examination601A6024 hours take home online exam. One essay question from a choice of three
Other Assessment
Description Semester When Set Percentage Comment
Prob solv exercises1M20Group exercise and presentation (45 minutes per group)
Prob solv exercises1M20Group exercise and presentation (45 minutes per group)
Assessment Rationale And Relationship

•       The written exam will test the knowledge of the students as related to all of the stated intended knowledge outcomes of the module.
•       The group working and presentations will test individual and group working abilities as well as presentation skills, the ability to put together complex information related to neuromuscular diseases, including experimental design and critical anaysis of related research, and the ability to communicate it effectively to their peers. The first group exercise and presentation will be on specific disease groups, providing analysis of molecular pathology of a nominated topic. The second group exercise and presentation will be on specific disease groups, providing analysis of therapeutic options of a nominated topic.

Reading Lists

Timetable