Romina Kohan

Rare Diseases (RDs) are more than 6,900 pathologies that affect fewer than 200,000 people in US, or less than 5 people/10,000 in the EU. Disease specific programs at a regional level could benefit the patients, and at the same time stimulate, coordinate and support research, facilitating drug and biologic products development for treatments. A Translational Program for the study of NCLs, a group of inherited neurodegenerative RDs, was implemented along the last 10 years at the Children´s Hospital in Córdoba-Argentina, integrating all key traits of knowledge (diagnoses, phenotypes/genotypes, care/palliative medicine, education/social aspects), and promoting families participation. An important clue was the international collaboration that enabled high technology inputs. The NCL-Program is a model approach on RDs in a middle income country. Forty two individuals were diagnosed and CLN2 was stated as the most frequent form (66.6%). Phenotypes/genotypes were revealed, allowing more effe...

Background: Colon cancer is one of the most important causes of death in the entire world. New pharmacological strategies are always needed, especially in resistant variants of this pathology. We have previously reported that drugs such as menadione (MEN), D, L-buthionine-S,R-sulfoximine or calcitriol, used in combination, enhanced cell sensibility of breast and colon tumour models, due to their ability to modify the oxidative status of the cells. Melatonin (MEL), a hormone regulating circadian rhythms, has anti-oxidant and anti-apoptotic properties at low concentrations, while at high doses, it has been shown to inhibit cancer cell growth. Objective: The objective of this study is to determine the antitumoral action of the combination MEN and MEL on colon cancer cells. Methods: Caco-2 cells were employed to evaluate the effects of both compounds, used alone or combined, on cellular growth/morphology, oxidative and nitrosative stress, and cell migration. Results: MEN plus MEL dramat...

Introduccion: Las Lipofuscinosis Ceroideas Neuronales (LCNs) son un grupo de patologias neurodegenerativas hereditarias de atesoramiento lisosomal (PALs) caracterizadas por el almacenamiento en los lisosomas de materiales complejos pobremente reconocidos. Su curso es muy severo con desenlace fatal, habiendo sido definidos diversos tipos sobre la base del estudio de los fenotipos clinicos, enzimaticos, morfologicos y las mutaciones. Su incidencia es de 1:12.500 nacimientos vivos a nivel mundial. Las intervenciones farmacologicas con moleculas pequenas han sido exitosas para algunas PALs; sin embargo, debido a que para cada una de las moleculas ha sido asumido un mecanismo de accion, la efectividad puede estar limitada a uno o a pocos desordenes y no beneficiar a otros. Se han comprobado efectos diversos de una serie de moleculas tales como Miglustat, Chaperonas moleculares disenadas, Clenbuterol, N-acetilcisteina (Mucomyst), Cisteamina, Gentamicina y PTC124. Los tratamientos farmacol...

Clinicians, basic researchers, representatives from pharma and families from around the world met in Cordoba, Argentina in October, 2014 to discuss recent research progress at the 14th International Congress on Neuronal Ceroid Lipofuscinoses (NCLs; Batten disease), a group of clinically overlapping fatal, inherited lysosomal disorders with primarily neurodegenerative symptoms. This brief review article will provide perspectives on the anticipated future directions of NCL basic and clinical research as we move towards improved diagnosis, care and treatment of NCL patients.

Noher de Halac, I and Cismondi, I and Kohan, R and Dodelson de Kremer, R and Guelbert, N and Muller, VJ and Cregeen, D and Canellli, N and Aiello, CC and Tapia Anzolini, V and Mole, S and Xin, W and Sims, K and Frietz, M and Santorelli, FM and Oller de Ramirez, ...

Palmitoyl Protein Thioesterase1 (PPT1) and Tripeptidyl Peptidase-I (TPP-I) are expressed in the human saliva. A reliable and non-invasive source for the diagnosis of infantile (CLN1) and late infantile (CLN2) neuronal ceroid lipofuscinoses. ... Kohan R, de Halac IN, Tapia ...

Palmitoyl Protein Thioesterase1 (PPT1) and Tripeptidyl Peptidase-I (TPP-I) are expressed in the human saliva. A reliable and non-invasive source for the diagnosis of infantile (CLN1) and late infantile (CLN2) neuronal ceroid lipofuscinoses. ... Kohan R, de Halac IN, Tapia ...

Introduction: The Neuronal Ceroid Lipofuscinoses (NCLs) are inherited neurodegenerative lysosomal diseases appearing in individuals of all ages.The accumulation of autofluorescent lipopigments in the brain and in peripheral tissues is themain characteristic of the NCL group. Themutated CLN8 is known to be associated with Progressive Epilepsy with Mental Retardation (EPMR) and variant Late Infantile (vLI) phenotypes. Aim: To characterize genetically CLN8 in Latin America. Methods: Fifteen individuals with CLN8 suspicion were tested by PCR, DNA sequencing and in silica analysis. Results: The previously registered c.685C>G change, assumed as the disease causing mutation in 2 subjects, is a frequent polymorphism in the Argentinean population. The c.1A>G mutation is a new pathogenic missense mutation, found in heterozygous state in 1/15 vLI individuals. This mutation affects the translation by losing the first methionine, producing downstream a new initiation codon, a frameshift an...

Introducción: Las LCNs son un grupo de enfermedades neurodegenerativas de herencia generalmente autosómica recesiva con inicio en la infancia, adolescencia o adultez, caracterizadas por la acumulación de lipopigmentos autofluorescentes principalmente en neuronas. Se reconocen 14 formas genéticas con 5 fenotipos clásicos y sus variantes. CLN8 es el gen que subyace a una forma prevalente en Escandinavia, la Epilepsia Progresiva con Retardo Mental y a una forma infantil tardía de Italia y Portugal. Pacientes con mutaciones en ese gen aun no han sido descriptos en América Latina, si bien se encontró un cambio aun no validado como mutación en el ADN de dos individuos de Argentina y México. Objetivo: -Estandarizar PCR para cada uno de los 3 exones del gen CLN8. -Analizar dicho gen en 15 pacientes compatibles con una LCNs y -Validar eventuales cambios genómicos nuevos, además de p.Pro229Ala hallada anteriormente. Sujetos y Métodos: En este trabajo se estudia por biología molecular el gen C...

INTRODUCTION: NCL, inherited neurodegenerative diseases of all ages, present storage of lipofuscin-like lipopigments in cerebral neurons and peripheral tissues. Mutations in CLN8 gene causing Epilepsy Progressive with Mental Retardation (EPMR) of Scandinavia and vLI phenotype in other countries, had not yet been described in Latin America. The change p.Pro229Ala, found in the DNA of 2 individuals from Argentina and Mexico, was not validated as a mutation. AIMS: To analyze and to validate changes in CLN8 gene in individuals suspected of vLINCL. Subjects: 15 individuals with normal PPT1 and TPP1 enzymes, positive electronic microscopy and lack of mutations in other NCL genes. METHODS: PCR, sequencing and bioinformatic analyses was performed on the coding region of CLN8 gene and validation of mutations was carried out on 200 controls alleles. RESULTS: The novel mutation c.1A>G, p.Met1Val, was validated for an Argentinean child with clinical suspicion of vLI, who presented age of ons...

Clinicians, basic researchers, representatives from pharma and families from around the world met in Cordoba,
Argentina in October, 2014 to discuss recent research progress at the 14th International Congress on Neuronal
Ceroid Lipofuscinoses (NCLs; Batten disease), a group of clinically overlapping fatal, inherited lysosomal disorders
with primarily neurodegenerative symptoms. This brief review articlewill provide perspectives on the anticipated
future directions of NCL basic and clinical research aswemove towards improved diagnosis, care and treatment of NCL patients.
This article is part of a Special Issue entitled: Current Research on the Neuronal Ceroid Lipofuscinoses (Batten
Disease).

This article addresses the educational issues associated with rare diseases (RD) and in particular the Neuronal Ceroid Lipofuscinoses (NCLs, or CLN diseases) in the curricula of Health Sciences and Professional's Training Programs. Our aim is to develop guidelines for improving scientific knowledge and practice in higher education and continuous learning programs. Rare diseases (RD) are collectively common in the general populationwith 1 in 17 people affected by a RDin their lifetime. Inherited defects in genes involved in metabolism are the commonest group of RD with over 8000 known inborn errors of metabolism. The majority of these diseases are neurodegenerative including the NCLs.
Any professional training program on NCL must take into account the medical, social and economic burdens
related to RDs. To address these challenges and find solutions to themit is necessary that individuals in the government and administrative authorities, academia, teaching hospitals and medical schools, the pharmaceutical
industry, investment community and patient advocacy groups all work together to achieve these goals. The logistical issues of including RD lectures in university curricula and in continuing medical education should reflect its complex nature. To evaluate the state of education in the RD field, a summary should be periodically up dated in order to assess the progress achieved in each country that signed up to the international conventions addressing RD issues in society. It is anticipated that auditing current practice will lead to higher standards and provide a framework for those educators involved in establishing RD teaching programs world-wide.