Neurogenética en el Perú, ejemplo de investigación traslacional

Mazzetti, Pilar; Inca‐Martinez, Miguel; Tirado-Hurtado, Indira; Milla-Neyra, Karina; Silva-Paredes, Gustavo; Vishnevetsky, Anastasia; Cornejo‐Olivas, Mario

doi:10.17843/rpmesp.2015.324.1773

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…The mean age at onset in our population is consistent with classical reports among the majority of other worldwide HD cohorts previously reported on [28, 29]. Furthermore, the high percentage of our population reporting official residence in Lima is likely related to the fact that the NRC-INCN is the national referral center for HD in the public healthcare system [30].…”

Section: Discussionsupporting

confidence: 89%

Economic burden of Huntington’s disease in Peru

Silva-Paredes¹,

Urbanos-Garrido

Inca‐Martinez

et al. 2019

BMC Health Serv Res

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BackgroundHuntington’s disease (HD) is a devastating and fatal neurodegenerative disorder that leads to progressive disability, and over time to total dependence. The economic impact of HD on patients living in developing countries like Peru is still unknown. This study aims to estimate the economic burden by estimating direct and indirect costs of Huntington’s disease in Peru, as well as the proportion of direct costs borne by patients and their families.MethodsDisease-cost cross-sectional study where 97 participants and their primary caregivers were interviewed using a common questionnaire. Prevalence and human capital approaches were used to estimate direct and indirect costs, respectively.ResultsThe average annual cost of HD reached USD 8120 per patient in 2015. Direct non-healthcare costs represented 78.3% of total cost, indirect costs 14.4% and direct healthcare costs the remaining 7.3%. The mean cost of HD increased with the degree of patient dependency: from USD 6572 for Barthel 4 & 5 (slight dependency and total independency, respectively) to USD 23,251 for Barthel 1 (total dependency). Direct costs were primarily financed by patients and their families.ConclusionsThe estimated annual cost of HD for Peruvian society reached USD 1.2 million in 2015. The cost impact of HD on patients and their families is very high, becoming catastrophic for most dependent patients, and thus making it essential to prioritize full coverage by the State.

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Section: Discussionsupporting

confidence: 89%

Economic burden of Huntington’s disease in Peru

Silva-Paredes¹,

Urbanos-Garrido

Inca‐Martinez

et al. 2019

BMC Health Serv Res

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“…The Neurogenetics Research Center (NRC) of the Instituto Nacional de Ciencias Neurologicas (INCN) in Lima, Peru, is a specialized center within the public neurologic institute that offers genetic testing and clinical care for patients with various neurogenetic disorders, with a particular focus on the large Peruvian HD population. 19 Outreach clinics are conducted by the NRC in the Cañete valley, a known focus of HD located approximately 3 hours south of Lima. 20 Patient data from outreach clinics in Cañete as well as outpatient visits at the NRC in Lima are aggregated in the NRC HD clinical database.…”

Section: Methods Settingmentioning

confidence: 99%

Juvenile‐Onset Huntington's Disease in Peru: A Case Series of 32 Patients

Vishnevetsky

Cornejo‐Olivas

Sarapura‐Castro

et al. 2022

Movement Disord Clin Pract

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Background Juvenile‐onset Huntington's Disease (JoHD) or Huntington's disease (HD) with age of onset ≤20 years, is a rare clinical entity that often differs phenotypically from adult HD and represents only 1–15% of total HD cases. Objective To characterize the genetic and clinical characteristics of 32 JoHD patients seen in a Peruvian Neurogenetics clinic from 2000–2018. Methods This study is a retrospective clinical and genetic review. The clinical database in Lima, Peru was searched for HD patients seen in clinic between 2000 and 2018. Inclusion criteria were: (1) genetically confirmed disease; and (2) HD age of onset ≤20 years, according to the documented medical history. Results Among 475 patients with genetically confirmed HD in the database, 32 patients (6.7%) had symptom onset at ≤20 years. Among JoHD patients with a known transmitting parent (30 of 32), paternal transmission accounted for 77% of cases. Anticipation was higher with paternal transmission compared to maternal transmission (27.5 ± 11.5 vs. 11.3 ± 7.1 years). Overall expanded CAG repeat length ranged from 44 to 110, with a mean length of 65.6 ± 15.4, and 14 (44%) cases had repeat length under 60. Of the 32 patients included in the study, 25 had detailed clinical symptomatology available, and many patients had unique clinical features such as prominent sleep disturbance (60% of patients), or parkinsonism (73%). Conclusions This large case series of JoHD patients characterizes the Peruvian JoHD population, reports on unique familial relationships in JoHD, and highlights the varied symptomatic presentation of this rare disease.

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“…3 [26] se realizó una minimización de energías para la estructura MBNL-1, usando el método de "steepest descent", seguidamente se tomó la estructura minimizada de la MBNL-1 y se procedió a realizar la Dinámica Molecular, agregándole condiciones periódicas de contorno (PBC) [27] usando la funcional CAMB3LYP [28], la cuál es una funcional híbrida de intercambio correlación que combina las cualidades híbridas del B3LYP y una corrección de largo alcance. Además de la funcional CAMB3LYP, se utilizó el set de base TZVP para obtener una convergencia más rápida y mejor de las energías y geometrías a nivel de DFT (Density Theory Function) [29] y así evitar las frecuencias negativas al momento de la optimización.…”

Section: B Optimización De Las Estructuras Mediante Mecánica Moleculunclassified

“…Tabla de scoring de la interacción MBNL-1 con espermidina. Se muestra los mejores 20 scores de 50 000 conformaciones 1 Scores del acoplamiento molecular 2 nergía total correspondiente al score 3 Energía de la conformación 4 Energía de la fuerza de interacción 5 Desviación media cuadrática…”

Section: Acoplamiento Molecular Entre El Mbnl-1 Y Launclassified

“…La investigación de la neurogenética en el Perú lleva un desarrollo fructífero de aproximadamente 20 años, sin embargo, aún presenta muchos desafíos por cumplir; siendo el centro de Investigación Básica en Neurogenética (CIBN) perteneciente al Instituto Nacional de Ciencias Neurológicas (INCN) el único centro de investigación que se dedica a la neurogenética en el Perú [3]. Según el informe del INCN en el periodo del 2010 al 2014 existió un incremento en el número de citas por trastornos en neurogenética, estando entre ellas los pacientes con distrofia miotónica (DM) también conocida como distrofia miotónica tipo 1 (DM1) [4].…”

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Esperdimina como agente inhibidor de la proteína de la distrofia muscular miotónica tipo 1 (MBNL‐1) empleando química computacional

Terrones

2017

TEC

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RESUMENLa Espermidina es un poliamina que podemos encontrar en frutas, verduras, productos cárnicos y lácteos; además de ser conocida por su papel modulador de funciones del ADN, ARN, nucleótidos trifosfatos y proteínas. Según, estudios experimentales recientes demostraron que cumple una función inhibitoria sobre la proteína relacionada con la patogénesis de la distrofia miotónica tipo 1 (MBNL-1) dando luces a esta enfermedad aun sin cura; sin embargo, estos estudios no han proporcionado suficientes datos para aclarar su capacidad inhibitoria. En este trabajo se comprobó la interacción existente entre la espermidina y la proteína MBNL-1 mediante química computacional. El análisis mediante el uso de mecánica cuántica (QM) se llevó a cabo con la funcional CAM-B3LYP usando un set de base TZVP. En relación a la mecánica molecular (MM) se utilizó un campo de fuerza OPLS-aa, seguidamente se realizó una solvatación de la proteína MBNL-1 estabilizándose en menos de 0.3nm. Se empleó un ensamble canónico NVT donde la temperatura, número de moles y volumen permanecieron constantes asemejando así la simulación a una temperatura fisiológica a la del ser humano. Adicionalmente, el análisis de Ramachandran permitió validar la estructura la cual se conservó a través del tiempo (100ns) obteniendo un 98.4% de certeza. Finalmente quedó demostrado que la interacción in silico de la espermidina-MBNL-1 fue tan semejante como la interacción reportada in vivo e in vitro.Palabras Clave: Agente inhibidor, distrofia miotónica tipo 1, espermidina, mecánica cuántica, mecánica molecular, química computacional. ABSTRACTSpermidine is a polyamine compound found in fruits, vegetables, meats and milk products. It is also known for its role as a modulator of functions for DNA, RNA, nucleotide triphosphates and proteins. Some recent experimental studies have shown that it has an inhibitory function on the protein related to the pathogenesis of myotonic dystrophy type 1 (MBNL-1), providing some hope in relation to this disease presently without cure. However these studies have not provided sufficient information to explain its inhibitory role. In the present work, the existing interaction between spermidine and the MBNL-1 protein has been confirmed by computational chemistry. The quantum mechanics analysis was carried out with the CAM-B3LYP density functional, using a TZVP basis set. For the molecular mechanics, the OPLS-AA force field was used, followed immediately by the solvation of the MBNL-1 protein, which stabilized at less than 0.3 nm. As an NVT canonical ensemble (constant volume, temperature and number of moles) was used, the process can simulate what is happening at the physiological temperature of a human body. Furthermore, a Ramachandran analysis allowed the validation of the structure, which was preserved through time (100 ns), at a 98.4 % confidence level. It was therefore demonstrated that the in silico interaction between spermidine and the MBNL-1 protein was similar to the reported interactions in vivo and in vitro.

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Neurogenética en el Perú, ejemplo de investigación traslacional

Cited by 5 publications

References 15 publications

Economic burden of Huntington’s disease in Peru

Economic burden of Huntington’s disease in Peru

Juvenile‐Onset Huntington's Disease in Peru: A Case Series of 32 Patients

Esperdimina como agente inhibidor de la proteína de la distrofia muscular miotónica tipo 1 (MBNL‐1) empleando química computacional

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