Navigating Rare Diseases: Current Research Trends and Coping Strategies for Patients

What is a Rare Disease?

A rare disease is a rare condition that affects a small percentage of the population. According to WHO, a disease is rare if it affects fewer than 5 in 10.000 people. Despite being uncommon, there are thousands of rare diseases, and they collectively affect millions of individuals. 

Let’s take a look at some of the most common rare diseases: 

  • Cystic fibrosis: a genetic disease caused by a mutation in a gene called CFTR. The protein that is produced by this gene makes the mucus in our body thin and slippery. When the gene has a mutation, the protein becomes non-functional, and the mucus becomes thick and sticky. This mucus builds up, causing blockages, damage or infections in the lungs and other organs. It affects approximately 100.000 people in the world. 
  • Amyotrophic Lateral Sclerosis (ALS): a progressive neurological disorder that affects the motor neurons responsible for controlling muscle movement. It causes muscles to weaken and waste away over time, often starting with difficulties in lifting objects or swallowing, and eventually leading to paralysis. When breathing becomes affected, it can result in death. Remember the Ice Bucket Challenge that went viral a few years ago? That was to raise awareness for ALS. The cold water makes an intense sensation that can be surprising and uncomfortable. This discomfort was used to metaphorically represent the persistent and often debilitating symptoms of ALS, which affect a person’s ability to move and breathe. ALS affects approximately 450.000 people worldwide. 
  • Huntington’s Disease: a genetic disorder that affects the HTT gene which leads to abnormal production of huntingtin protein, causing it to accumulate in brain cells. It is a hereditary disease that causes involuntary and spasmodic movements, decline in cognitive functions affecting a person’s ability to make decisions and memorize, as well emotional changes such as depression, irritability or anxiety. It affects roughly 200.000 – 300.000 people in the world.  
  • Hemolytic-Uremic Syndrome (HUS): a condition often of infection by a specific bacterium, which produces a toxin that leads to kidney failure, low red blood cells (anemia) and low platelets which increases the risk of bleeding. People get infected with these bacteria primarily by consuming undercooked or contaminated food, especially beef, or drinking contaminated water. Globally, HUS affects approximately 45.000 to 90.000 people annually. 
  • Hemophilia: a genetic disorder where the blood doesn’t clot normally due to a mutation in the genes responsible for producing substances known as clotting factors, which are involved in the clotting process.  These mutations lead to a deficiency or disfunction of specific clotting proteins. In Hemophilia A there is a deficiency of clotting factor VIII, while Hemophilia B involves a deficiency of clotting factor IX. They cause easy bruising, frequent nosebleeds and bleeding that doesn’t stop quickly.  It is estimated that around 400.000 people in the world are affected by hemophilia.  
  • Rare autoimmune diseases a disease is referred to as “autoimmune” when our immune system attacks our body’s cells. While many people are affected by autoimmune diseases, there are numerous different types, and many of them are considered rare because they affect a very small number of people. For example, in Goodpasture Syndrome our immune system produces antibodies against a protein present in our kidneys and lungs. This leads to damage to these organs and can lead to kidney failure. This syndrome affects about 2.000 to 4.000 people annually.  

Rare Disease Research  

Most rare diseases are caused by mutations or changes in one or more genes, often inherited from our parents. For this reason, many rare disease treatments are based on gene therapy, which is a technique that tries to modify a particular gene inside our body. 

Despite the rarity of these diseases, medical knowledge and diagnostic techniques are advancing. For example, we now know that cystic fibrosis is caused by a mutation in CFTR gene, which is passed down from parents to their children. In the case of cystic fibrosis, to have the disease, you need to have 2 sets of the mutated CFTR gene, one from each parent. People with only one mutated gene are called “carriers”. Carriers won’t have the disease, or symptoms, but could pass the mutated gene to their children. Therefore, for a child to develop cystic fibrosis, both parents must either have the disease, or both be carriers of the mutated gene. We also know that because of the severity of the condition, and the need for early treatment, early detection is key. Nowadays, newborns are tested for this disease, which involves a blood test that measures levels of a protein called IRT, which is elevated in patients with cystic fibrosis. If the result is positive, genetic tests are conducted to confirm the diagnosis.  

While many rare diseases are a result of mutations, we cannot forget that some of them are caused by microorganisms such as bacteria, viruses, fungi or parasites. For example, Buruli Ulcer, a rare bacterial infection that causes severe disfiguration, is caused by Mycobacterium ulcerans while Histoplasmosis is an infection caused by the inhalation of spores of the fungus Histoplasma capsulatum. In those cases, we should look for a treatment that involves antibiotics, antifungal medications or antitoxins, depending on the illness.  

However, there are several rare diseases which we do not know the cause of. 

Challenges in Clinical Trials for Rare Diseases

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In most cases, clinical trials are designed for a specific type of patient, with a specific gene and a specific therapy, in turn creating many challenges:   

  1. Recruiting Participants: there are very few people affected by a specific rare disease, and they are often distributed around the globe, making it difficult to find enough participants. 
  1. High Costs: caused by the distribution of the patients but as well as because specialized facilities and expert staff are needed, as well as the cost of developing a unique therapy 
  1. Funding Limitations: in the case of rare diseases, only a few people will benefit from the treatment, which means that the economic benefit is uncertain. This uncertainty, along with the high costs involved, makes it difficult to attract financial support. 
  1. Limited Disease Knowledge: understanding which specific gene is involved in the disease can be difficult, complicating the development of targeted treatments. 
  1. Regulatory Concerns: obtaining approval for clinical trials can be complex due to the innovative nature of some therapies, which may be unfamiliar to regulatory agencies. 

Emotional Impact of Living with Rare Illnesses 

Families of children with rare diseases tend to have higher levels of anxiety and depression compared to families of children with more common chronic conditions. This is because dealing with rare diseases often involves a long and uncertain diagnostic process and a lack of information and support, and no guarantee that treatment will be available or even exist.  

For example, children with HUS often require hospitalization in a pediatric intensive care unit, and those with kidney failure may need dialysis or even a kidney transplant. Those children may feel overwhelmed by the multiple medications, diet restrictions and the hospital visits. This can lead to anxiety and depression, not just for them but also for their parents. Parents may experience guilt related to their child’s condition, especially regarding any possible causes, and frustration with managing their child’s illness.  

Future of Research: Breakthroughs 

Each Rare disease affects small numbers of patients worldwide, but it is important not to ignore those patients and to conduct research to improve their quality of life, because they have very limited treatment options. This research should not only be focused on treatment but also on improvement of diagnostic methods and prevention. Every patient’s well-being matter, and dedicated research can make a significant difference in their lives. 

Awareness campaigns play a key role in raising public knowledge of rare diseases, which can drive funding and support research. Media coverage of a specific rare disease can attract investors and researchers to focus on a disease. For example, the ice bucket challenge for ALS raised over $220 million worldwide and increased public awareness of ALS. The funds raised contributed to the discovery of new genes linked to the disease. ALS isn’t the only rare disease that has made the spotlight, though. Recently a new gene-editing technology has been developed, called CRISPR-Cas9, that can potentially fix genetic problems. This technology works like scissors, cutting specific faulty sections of our genes and replacing them with correct ones.  

Another important breakthrough is the development of a gene therapy to treat Spinal Muscular Atrophy (SMA), a rare genetic disease that affects muscle control and movement caused by the mutation in a gene called SMN1.  

Even though there have been significant breakthroughs in the treatment of rare diseases, much more research is needed. Rare diseases continue to present unique challenges, with many patients having limited treatment options and facing difficulties in obtaining accurate diagnoses. Continued scientific investigation, public awareness, and funding are crucial to unlocking new therapeutic possibilities and improving the lives of those affected by these conditions. Every patient deserves hope, and ongoing research can bring us closer to that goal.