A patient journey perspective for individuals and families affected by LGMD

Gene therapy is becoming a more accessible treatment for LGMD. It is a treatment that addresses the cause of LGMD, with the potential to change the disease. This can raise many questions. Some are medical, some are practical, and some deeply personal. This educational brochure has been created to make gene therapy easier to understand and to offer clear, accessible information for people living with LGMD, their families, and everyone involved in their care. Throughout this brochure, you will find QR codes that link to a series of short educational videos. These videos are hosted by Kaya, who has a rare combination of personal experience and scientific understanding.

Kaya is living with LGMD2D/R3 and participated in a gene therapy trial in 2015. He also has a degree in biomedical sciences and is currently studying Regenerative Medicine and Technology. This gives him a unique perspective. He understands the science behind gene therapy, but also the emotional, practical and personal questions that can come with it. The goal of this brochure and video series is not to replace conversations with doctors, specialists or care teams. Instead, it is meant to support those conversations. The videos can help explain key concepts, answer common questions, and make it easier to discuss this important topic with the people around you. You can watch the videos in your own time, return to them whenever needed, and share them with family members, friends or healthcare professionals. Together, this brochure and video series offer a simple and accessible way to learn more about LGMD-care, research, and the developments that may shape the future.

Diagnostics as a steppingstone for treatment options

Before gene therapy or clinical trial eligibility can be discussed properly, doctors first need to understand the diagnosis as clearly as possible. For people with LGMD, this usually starts with confirming the exact genetic cause of the disease. A confirmed genetic diagnosis is important because LGMD is not one single disease. It is a group of genetic muscle diseases, and treatments or clinical trials are developed for specific LGMD subtypes. Alongside genetic testing, doctors may also use other tests to better understand how the disease affects the body. As a patient it is very important that you are aware of your LGMD subtype, this makes finding and receiving adequate care, and possibly treatments, much easier.

Genetic diagnosis
To confirm an LGMD diagnosis, blood or saliva is tested. The test can look either at the whole DNA (WGS) or targeted gene panels. The identification of a variant does not necessarily mean that a diagnosis is confirmed, this depends on other factors, including the exact variant, the inheritance pattern and the clinical context. It is also possible that the test is inconclusive or shows a variant of unknown significance (VUS). In these cases, further testing may be done. The database of known mutations is growing, so inconclusive results may be solved in the future.

Muscle biopsy
Before genetic testing, muscle biopsies were a big part of an LGMD diagnosis. A muscle biopsy is a test where a small piece of muscle tissue is taken and examined in a laboratory. Doctors may use it to look for signs of muscle damage or to study whether certain muscle proteins are present, reduced or missing. This can also be used to test the effect of gene therapy. It’s very common that a trial includes a baseline biopsy before the treatment and a biopsy a few months after gene therapy. Luckily, muscle biopsies can be taken with a small needle nowadays. This is less invasive than a traditional open muscle biopsy because the tissue is collected with a needle rather than a larger incision. Traditional biopsies may still be necessary for certain tests where a needle biopsy does not yield enough tissue or information. 

MRI
MRI stands for Magnetic Resonance Imaging. An MRI scan can create detailed images of the muscles inside the body. MRI can help doctors see which muscles are affected and whether there is a pattern that fits a certain LGMD subtype. MRI may also help follow changes over time. For this reason, MRI testing is often part of a clinical trial too.

Why these tests matter
Diagnostics are not only about giving the disease a name. They help patients, families and doctors understand the condition more clearly. The right diagnosis can support better follow-up care, help monitor changes over time and, in some cases, help determine whether someone may be eligible for a clinical trial or treatment option.

What is gene therapy?

‘Gene therapy’ is a broad term. It does not describe one single treatment. Different approaches work in different ways, depending on the disease, the gene, and the delivery method. LGMD is caused by mutations in specific genes. These genetic changes can lead to missing or faulty proteins that affect muscle function. Gene therapy aims to address part of this process by delivering genetic instructions to cells, using a delivery system called a ‘vector’. Many LGMD gene therapy studies use AAV vectors. These are adapted viruses designed to carry genetic material into the body, with the nucleus of muscle cells as target destination. After this genetic material enters the nucleus, it generally becomes a stable circular episome that can produce the missing protein for a long time, without integrating into the human DNA. Integration into the human DNA does happen, but at a very low frequency. Other approaches, such as gene editing or different delivery systems such as non-viral lipid nanoparticles (LNPs), are also being researched. Gene therapy is a medical treatment with possible benefits, possible risks and many important questions that need to be discussed carefully with a healthcare team prior to treatment.

Benefits, risks and realistic expectations

Gene therapy can bring hope, especially for people living with a progressive disease. But hope needs to be built from clear and realistic information. Responses to gene therapy can differ wildly from person to person, this can make it difficult to set realistic expectations for the treatment whether you are participating for yourself or to help the community. There can also be risks. Gene therapy can affect the immune system, liver, muscles or other parts of the body. In some neuromuscular gene therapy studies, serious adverse events have been reported. Understanding possible benefits and risks is essential before making decisions. This is accomplished via a document known as informed consent which, among other things, explains the to the patient important information about the study. Such as what is known, what is unknown, what your rights are and what happens if you want to stop.

Eligibility and clinical trials

One of the most difficult parts of gene therapy is that not everyone is eligible. Eligibility is about safety, study design and whether the treatment is intended for a specific genetic diagnosis, mutation, age group, disease stage or medical situation. Currently, LGMD patients mainly get access to gene therapy through clinical trials. A clinical trial is research. It is designed to ensure patient safety and to answer questions about safety, dosing, possible benefits and side effects. Taking part in a trial may involve many hospital visits, tests, assessments and long-term follow-up. They usually have strict inclusion and exclusion criteria. Factors such as antibodies, mobility, age, disease stage, heart or lung function, previous treatments and other health conditions can influence eligibility. Clinical trials may also include a placebo group. Here, patients get a ‘pretend’ treatment and are tested alongside patients who have gotten the real treatment. After the testing, the placebo group may receive the real treatment. This can take some time or, in some cases, the placebo group may not receive the active therapy at all. It is very important that patients are aware of the study design before choosing to participate.

The treatment journey and real-life impact

Gene therapy is often imagined as one treatment day. In reality, it’s a  multi-step process over a span of months or even years, which can start way before the actual treatment and continue long after. The administration of gene therapy differs per case, ranging from a simple IV infusion to more elaborate methods, depending on what part of the body the researchers are targeting. After treatment, monitoring is very important. There may be regular hospital visits, blood tests, medication, symptom reporting and follow-up for a period of time. This can affect school, work, family life, travel and future plans. Besides the treatment journey itself, is the emotional side. Patients and families may feel hope, fear, pressure, uncertainty or disappointment. Parents may struggle with having to make decisions for their child. Young people may wonder how treatment could affect their future. Families need support from schools, employers, caregivers and mental health professionals. Gene therapy decisions do not happen only in the hospital. They affect real lives, with real responsibilities and emotions. Good preparation, clear communication and support from others make a meaningful difference.

Navigating mental wellbeing

Mental wellbeing is an important part of the gene therapy journey and deserves just as much attention as the medical and practical aspects of treatment. Patients and families may experience a complex mix of hope, uncertainty, fear, pressure and changing expectations before, during and after treatment. These emotions can be influenced by many things: the decision whether or not to participate in a trial, uncertainty about possible outcomes, repeated hospital visits and testing, recovery, fatigue, or simply the feeling that others are watching closely for signs of improvement. For younger patients, school, friendships and growing independence can add another layer. Parents and caregivers may experience their own uncertainty while trying to support someone else and make the best possible decisions. Talking openly about these feelings can help. Mental and emotional support should be considered part of the overall treatment journey, not something that is only discussed when a problem occurs.

The series has been developed by the LGMD CAB to help make complex information more understandable and to support informed conversations between people living with LGMD, their families, clinicians and the wider community.

Stay Informed. Stay Connected

This educational brochure and video series are developed for people living with LGMD, their families, caregivers, educators and the wider NMD community. The goal is to make complex information about gene therapy and related topics more understandable from a patient journey perspective. Gene therapy is a developing field, and there is always more to learn. Use this information as a starting point for your own journey and to explore the questions that matter to you.

Connect with us and explore the latest information and resources. By staying connected and sharing knowledge, we can help you feel better informed and more confident in making the decisions that are right for you.

Educational brochure and video series are made possible with support from AskBio’s educational grant.

Disclaimer: This material is for educational purposes only. It does not provide medical advice and should not be used to make treatment decisions without speaking to a qualified healthcare professional. Every person’s diagnosis, eligibility, risks and treatment options are different.