Attending the unattended: focusing on rare diseases

foto Patricia Setton
Patricia Setton

Departamento de Química Biológica, FFyB, IQUIFIB, UBA-CONICET

Juan Ferrario


The expression ‘‘rare diseases’’ describes a group of pathologies with a very low prevalence which brings about reduced incentives and support for fully investigation as well as appropriate managed by health professionals and in some cases lack of successful therapies. Rare diseases encompass a broad spectrum of pathologies which are defined considering their prevalence rather than by common biochemical, clinical and/or pathophysiological characteristics. Although “rare diseases” highlight the low frequency of this pathologies, bibliographical data reports around 6000 “rare diseases” which altogether affect close to 300 million people worldwide. Including in this group of pathologies are rare genetic diseases which affect the nervous system chronically with a progressive degenerative evolution, generally beginning during the newborn period or during childhood. In the present symposium we will focus on these group of pathologies emphasizing basic research performed to develop experimental models for the study of new therapeutic strategies or to shed light to the mechanisms underlying their pathophysiology, trying to pay attention to these unattended pathologies. Finally, an overview of the situation in Argentina will be presented.

Travelling axons, moving eyes

Sarah Guthrie

School of Life Sciences, University of Sussex

The ocular motor system controls eye movements consisting of three cranial nerves connected to six extraocular muscles. A precise sequence of axon guidance events is required for the development of the ocular motor system. The signalling protein alpha2-chimaerin (α2-CHN) plays a pivotal role in the formation of the ocular motor system; mutations in CHN1, encoding α2-CHN, cause the human eye movement disorder Duane Retraction Syndrome (DRS). Our research has demonstrated that manipulation of α2-chn signalling in the zebrafish embryo leads to ocular motor axon wiring defects. We have recently shown that several cytoskeletal regulatory proteins – collapsin response mediator protein 2 (CRMP2), (encoded by the gene dpysl2), stathmin1 and stathmin 2 – bind to α2-CHN. dpysl2, stathmin1 and especially stathmin2 are expressed by ocular motor neurons. Manipulation of dpysl2 and of stathmins in zebrafish larvae leads to defects in both the axon wiring of the ocular motor system and the optokinetic reflex, impairing horizontal eye movements. Knockdowns of these molecules in zebrafish larvae caused axon guidance phenotypes that included defasciculation and ectopic branching; in some cases these phenotypes were reminiscent of DRS. chn1 knockdown phenotypes were rescued by overexpression of CRMP2 and STMN1, suggesting that these proteins act in the same signalling pathway. These findings suggest that CRMP2 and stathmins signal downstream of α2-CHN to orchestrate ocular motor axon gu

Neurological manifestations in Fabry disease with a perspective on new therapies?

Derrralynn Hughes

University College London


Fabry disease (FD) (OMIM#301500) is an X-linked lysosomal storage disorder caused by a mutation in the GLA gene which leads to a deficiency of the enzyme alpha-galactosidase A. This impairment causes the accumulation of sphingolipids in cells from different tissues and organs, particularly globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) and causes dysfunction of various organs including the heart and kidney. FD may also affect the central and peripheral nervous system leading to stroke, white matter lesions, pain, and autonomic disturbance. Manifestations are heterogeneous with an early classical form of the disease generally presenting with acroparasthesia, sweating abnormalities and eye changes before progressing to renal dysfunction and cardiomyopathy; and a later onset form generally affecting to a single organ, notably the heart. Disease in males is usually proceeds that in females and is more severe. Stroke occurs sporadically in classical and later onset patients however features predicating the occurrence of neurological disease are not well understood. Whilst there is evidence of some effect of Fabry-specific therapy on manifestation such as pain, gastrointestinal disturbance and hearing loss data relating to central neurological events is more limited. A number of new therapies are under development and understanding of their potential impact on neurological manifestations is awaited.

CRISPR/Cas9 for the development of cellular models of lisosomal disorders

Paula Rozenfeld


Lysosomal disorders are a group of genetic disorders due to defects in the function of proteins, mainly enzymes, of lysosomes, characterized by accumulation of undegraded substrates in those organelles. Pathophysiological mechanisms that are fired from the genetic defect causing loss of organ function is not completely understood. Knowledge of these mechanisms at molecular level would lead to propose coadjuvant therapies directed to specific targets. For this reason, it is necessary to have in vitro or in vivo models of disease. We have developed cellular models of Gaucher disease by the use of gene editing technology of CRISPR/Cas9 directed to GBA1 gene. We have transfected two cell lines. One is the human monocytic cells THP-1 that are the precursors of macrophages, the main affected cell in Gaucher disease. The other is the U87 glioblastoma cell line, for the evaluation of neurological aspects associated to development of Parkinson disease in Gacuher patients.

Rare Diseases in Argentina

Romina Armando

Dr. Romina Armando, Geneticist, Rare Diseases Programa, Ministry of Health

Rare Diseases (RD) has become a new concept in public health. They are a heterogeneous group of pathologies with a very low prevalence in the population. Although few people is affected by each disease, all together they affect more than 3 million argentinian people. In Argentina, the National Law 26689 defines them as those entities whose prevalence is less than 1:2000. It is estimated that there are, at present, approximately more than 6000 different RD, most of them chronic, disabling and approximately 80% of genetic etiology. Despite the fact that they are different entities with diverse clinical presentation, the problems they promote both for the health system and for patients and their families are common (diagnostic delay, visit by many specialists, lack of information, etc.). This scenario triggered other countries to seek solutions by implementing a series of public policies with new strategies that allow the creation of processes and structures aimed at improving the life of patients, families and professionals. In Argentina, since 2015 with the creation of a National Program for RD in the Ministry of Health, strategic lines have been developed to simplify access to health care for patients affected with RD.