Since 2008, the World Day for Rare Diseases has been celebrated on February 28th with the purpose of raising awareness and helping all people suffering from any of the so-called "rare" diseases, so that they can receive the proper diagnosis and treatment and thus be able to lead a better life. This date was chosen because the month of February is very particular, "rare", as some years it has 28 days and others 29. Therefore, the World Day for Rare Diseases is celebrated every February 28 or 29, depending on whether or not we are in a leap year.
Lluis Montoliu pointed out that the translation of the English "rare" has been very unfortunate. "Rare diseases" should have been translated as "uncommon diseases". The adjective "rare" could be hurtful, negative, and even discriminate and separate the affected people and their families. Rare diseases should really be called low prevalence diseases, as they are pathologies that affect less than 5 people per 10,000 inhabitants.
The Spanish Federation of Rare Diseases (FEDER) indicates on its website that it is estimated that there are more than 7,000 rare diseases, of which 6,172 have already been identified, according to Orphanet data. Each rare disease is highly variable in terms of prevalence. There are more common rare diseases, such as cystic fibrosis, the most common genetic disorder among Caucasian children, which affects at least 1 in 8,000 people. In other cases, the population affected by a rare disease is much lower. For example, in achromatopsia or color blindness (individuals do not perceive colors, only shades of gray) the estimated frequency in the population is 1-9 per 100,000 people. 80% of rare diseases have a genetic origin, in some cases still unknown. The difficulty in providing an accurate diagnosis and the scarcity of treatments are common problems in these pathologies.
At the IIBM there are eleven groups working on rare diseases. They collaborate with hospital research groups to develop functional and genetic assays, as well as to search for new treatments, i.e. the research carried out at the IIBM has a strong translational component. Very important is also the cooperation with patient associations that are very involved in the work developed by the researchers.
The following is a summary of the work carried out by the IIBM groups in rare diseases.
Autophagy Associated Diseases Group. Drs. Ricardo Escalante Hernández and Oliver Vincent
Drs. Escalante and Vincent's group studies the molecular basis of rare diseases related to the autophagy process. They are currently working on BPAN (Beta Propeller-associated neurodegeneration) and ChAC (Chorea-acanthocytosis), two neurodegenerative diseases without effective treatment. They use model microorganisms and human cell lines to understand the molecular and cellular function of genes involved in these diseases and characterize the effect of mutations identified in patients. If you want to know more you can read their web page
Molecular Mechanisms of Mitochondrial Pathophysiology Group. Dr. Miguel Fernández Moreno
Mitochondrial diseases (MD) are those caused by functional alterations of the OXPHOS system, formed by the four complexes of the respiratory chain (Complexes I-IV) plus ATP synthase or Complex V. Although individually they are considered rare diseases, MDs together constitute the largest group of inborn errors of metabolism. The MDs are genetically and clinically very heterogeneous, and manifest with a single reasonably mild symptom such as deafness or exercise intolerance, or in the form of devastating syndromes incompatible with life. These diseases can result from mutations in nuclear or mitochondrial genes. Dr. Fernández Moreno's group has several objectives: the identification of undescribed genes involved in the function of OXPHOS, the characterization of the molecular mechanism of action of a reduced group of proteins involved in a unique way in the synthesis of mitochondrial tRNAs, the study of the relationship between mitochondrial DNA and tumor genesis, and the development of animal models for the study of mitochondrial diseases.
Ciliopathies Group. Dr. Francesc García Gonzalo
Ciliopathies are rare genetic diseases caused by dysfunction of cilia, fine protrusions of the cell membrane formed by microtubules that can function as motors or sensors. Most ciliopathies affect the primary cilia, cellular antennae that detect optical, mechanical or chemical signals, depending on the cell type. To function properly, these antennae must first be tuned, i.e., the cilia must accumulate the receptors and mediators that will enable them to pick up the appropriate signals. In Dr. García Gonzalo's laboratory, they study the molecular mechanisms by which cells tune their cilia, as well as the pathogenic processes that interfere with such tuning in ciliopathies such as Joubert or Bardet-Biedl syndromes, whose symptoms include, among others, cognitive and motor deficits, blindness, renal cysts, obesity and polydactyly.
Thyroid Hormones and Central Nervous System Group. Dr. Ana Guadaño Ferraz
Dr. Ana Guadaño's group works in the study of Allan-Herndon-Dudley syndrome or MCT8 deficiency, a rare disease due to mutations in the thyroid hormone transporter MCT8. Her group aims to identify biomarkers for the brain pathophysiology of patients affected by this pathology, as well as the development of therapeutic strategies in mice model of the disease to prevent or improve neurological alterations.
New Targets in Neurodegeneration and Neuroprotection Group. Dr. Teresa Iglesias Vacas
Dr. Teresa Iglesias cloned the KIDINS220 gene, and with her team has been investigating the function of this gene in different neuropathologies. Recently, pathogenic variants of KIDINS220 have been identified that produce an infantile syndrome called SINO (Spastic paraplegia, Intellectual disability, Nystagmus and Obesity). It is a rare neurological disease associated with developmental delay, spastic paraplegia requiring the use of a wheelchair, intellectual disability, ophthalmologic disorders and obesity. SINO syndrome also causes an accumulation of fluid in the brain, or hydrocephalus. His group has discovered that mice deficient in Kidins220 also present hydrocephalus, and has also identified the mechanisms involved in this fluid accumulation. They are currently using experimental models to develop therapies for patients affected by this disease.
Parkinson's, ALS and Tauopathies Group: New Perspectives (Cure4Brain). Dr. Isabel Lastres-Becker
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), also called frontotemporal lobar degeneration (FTLD), are two intrinsically associated rare neurodegenerative diseases that overlap clinically, neuropathologically and, above all, genetically. One of the great challenges of Dr. Lastres-Becker's laboratory is to discover new therapeutic targets, whose pharmacological modulation can slow down or stop the degenerative processes in these devastating diseases.
Oxygen Homeostasis in the Cardiovascular System Group. Dr. Silvia Martín Puig
Dr. Martín Puig's group investigates the molecular mechanisms and genetic determinants involved in the development of Kawasaki disease (KD), a pediatric vasculitis of unknown origin and the main cause of childhood-acquired cardiovascular disease. A percentage of patients not treated in time, or with resistance to current clinical treatments, develop severe cardiovascular alterations, including coronary dilatations and aneurysms, thrombosis, cardiac inflammation and eventually myocardial infarction. This group email@example.com developed an animal model that recapitulates these alterations and is investigating how the hypoxia pathway is involved in the vascular and inflammatory pathogenesis of KD. In addition, they are trying to identify new genetic variants that may explain the increased risk of developing coronary aneurysms or resistance to treatment using massive sequencing techniques. The group is also investigating the molecular basis and genetic determinants of a new rare disease, Multisystem Inflammatory Syndrome in Children (MISC), which is a severe clinical manifestation associated with pediatric SARS-CoV2 infection and with overlapping symptomatology to KD.
Telomeric Diseases and Experimental Therapies Group. Drs. Rosario Perona Abellón, Rosa Guerrero-López and Leandro Sastre Garzón
he group coordinated by Dr. Leandro Sastre works on diseases related to telomere shortening, including dyskeratosis congenita and idiopathic pulmonary fibrosis. These pathologies are accelerated aging diseases of the skin, bone marrow and other organs. The most severe manifestations are anemia, immunoinsufficiency and pulmonary fibrosis, which pose a major threat to the lives of patients. This group is working on the diagnosis of the disease and on the search for new treatments to correct the current lack of curative treatments. Rosa Guerrero-López is also investigating the identification of genetic factors involved in the pathogenesis and susceptibility to the development of Rasmussen's encephalitis, an autoimmune-inflammatory disease of the central nervous system, within the framework of a collaborative project led by the Hospital Infantil Niño Jesús.
Genetics and Pathophysiological Mechanisms of Congenital Anomalies Group. Dr. Víctor Luis Ruiz-Pérez
Dr. Ruiz-Perez's group has a long experience in the research of rare diseases with developmental disorders with special emphasis on skeletal ciliopathies and syndromes associated with bone fragility. In their research they use a methodology that combines genetic techniques, such as the analysis of variants from exome sequencing, with the study of cellular or animal models appropriate to each pathology. The main objectives of their research are the identification of new genes causing developmental disorders, thus contributing to improve the diagnosis of these diseases, and the determination of the cellular and molecular mechanisms involved in each case, a knowledge that is essential for the development of new therapies.
Auditory Neuropathology and Myelinopathies Group. Drs. Isabel Varela Nieto, Silvia Murillo Cuesta, Ana María Jiménez Lara and José Miguel Cosgaya Manrique
The laboratory coordinated by Dr. Isabel Varela works on the study of hearing loss and myelinopathies. Among the causes of hearing loss there are those of genetic etiology and those acquired, including early hearing aging and hypoacusis due to noise exposure, among others, which also have a strong component of genetic predisposition. Many of these hypoacusis are rare diseases due to their low individual prevalence. The group also studies schwannomas, rare tumor myelinopathies that can affect the auditory-vestibular nerve and produce hearing loss. Its objectives are to understand the genetic, molecular and cellular basis of these diseases, to develop new therapeutic strategies and to carry out preclinical trials in various experimental models to evaluate their efficacy.
Preclinical Models and New Therapies Group. Dr. Juan Manuel Zapata Hernández
Dr. Zapata's group investigates two rare diseases, chronic lymphocytic leukemia (CLL) and MULIBREY growth disorder or Perheentupa syndrome. CLL is still an incurable disease. They generate murine models of this leukemia to understand its etiology and evolution, and search for new drugs effective against patient cells resistant to current treatments. MULIBREY growth disorder, caused by mutations in the TRIM37 gene, is an extremely rare disease characterized by growth restriction and other multiorgan manifestations. This group studies the role of TRIM37 in the regulation of the innate immune response in non-lymphoid cells through cellular and murine models.