Estudio del mercado de futuros medicamentos y biomarcadores oculares, basado en análisis de datos de propiedad intelectual y de ensayos clínicos

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Óptica y Optometría, Departamento de Bioquímica y Biología Molecular IV, leída el 02-12-2016Durante esta tesis doctoral, hemos buscado nuevas vías de investigación, que podrían ayudar a la industria farmacéutica-oftalmológica a organizar su estrategia a largo plazo, adaptándose a la evolución de las tendencias internacionales en I+D. En este sentido, hemos investigado la dirección y el futuro del mercado de medicamentos y biomarcadores a nivel ocular, basándonos en información adquirida del análisis de las patentes publicadas y de ensayos clínicos en curso. En la realización de este estudio se ha investigado la aparición de posibles biomarcadores de glaucoma, con potencial para el diagnóstico, seguimiento y evaluación de esta patología y nuevos tratamientos que están actualmente en desarrollo. El glaucoma es una enfermedad ocular, que causa la degeneración progresiva de las células ganglionares y daño en el nervio óptico. Como consecuencia de estos eventos se produce una pérdida progresiva e irreversible del campo visual que desemboca en una ceguera permanente no tratable. Frecuentemente el avance de la enfermedad es imperceptible para el paciente, que acude al especialista cuando la patología se encuentra en un estadio avanzado. La causa exacta del glaucoma es incierta. Existen indicios de que la presión intraocular elevada está relacionada con la mayoría de los casos de glaucoma. Por lo tanto, el control de la presión intraocular sigue siendo el principal aspecto tratable en la terapia antiglaucomatosa. La mayoría de los casos de glaucoma pueden ser controlados y detener la pérdida de la visión mediante el tratamiento...During this thesis, we have sought new avenues of research that could support pharmaceutical ophthalmological industry to organize their long-term strategy, adapted to the changing trends in Research & Development. In this sense, we have explored the course and future of the ophthalmological pharmaceutical and biomarkers market, based on analysis of information acquired through published patents and ongoing clinical trials. The analysis of information revealed the development of novel molecules and new prospects for the ongoing research of the sector. The results demonstrate the existence of promising strategies in the short and long term for the development of new ocular drugs. Objectives This thesis is focused on the study of pharmacological innovation of glaucomatous neuropathies, which is the second leading cause of blindness worldwide, and the dry eye syndrome, which is an ocular surface pathology where the number of cases is rising significantly today. Results & Conclusions Glaucoma is an eye disease that causes progressive degeneration of ganglion cells leading to optic nerve damage. As a result of these events occurs a progressive and irreversible loss of visual field, leading to a permanent untreatable blindness. Often the disease progression is imperceptible to the patient who comes to the specialist when the disease is at an advanced stage. The exact cause of glaucoma is uncertain, even though there is evidence that elevated intraocular pressure is associated with most cases of glaucoma. Therefore, control of intraocular pressure remains the main aspect treatable in antiglaucoma therapy today. Most cases of glaucoma can be controlled and stop vision loss by treatment...Unidad Docente de Bioquímica y Biología MolecularFac. de Óptica y OptometríaTRUEunpu

Estudio del mercado de futuros medicamentos y biomarcadores oculares, basado en análisis de datos de propiedad intelectual y de ensayos clínicos

Durante esta tesis doctoral, hemos buscado nuevas vías de investigación, que podrían ayudar a la industria farmacéutica-oftalmológica a organizar su estrategia a largo plazo, adaptándose a la evolución de las tendencias internacionales en I+D. En este sentido, hemos investigado la dirección y el futuro del mercado de medicamentos y biomarcadores a nivel ocular, basándonos en información adquirida del análisis de las patentes publicadas y de ensayos clínicos en curso. En la realización de este estudio se ha investigado la aparición de posibles biomarcadores de glaucoma, con potencial para el diagnóstico, seguimiento y evaluación de esta patología y nuevos tratamientos que están actualmente en desarrollo. El glaucoma es una enfermedad ocular, que causa la degeneración progresiva de las células ganglionares y daño en el nervio óptico. Como consecuencia de estos eventos se produce una pérdida progresiva e irreversible del campo visual que desemboca en una ceguera permanente no tratable. Frecuentemente el avance de la enfermedad es imperceptible para el paciente, que acude al especialista cuando la patología se encuentra en un estadio avanzado. La causa exacta del glaucoma es incierta. Existen indicios de que la presión intraocular elevada está relacionada con la mayoría de los casos de glaucoma. Por lo tanto, el control de la presión intraocular sigue siendo el principal aspecto tratable en la terapia antiglaucomatosa. La mayoría de los casos de glaucoma pueden ser controlados y detener la pérdida de la visión mediante el tratamiento..

Recent developments on dry eye disease treatment compounds

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film

Fármacos de la enfermedad de ojo seco actualmente en evaluación de ensayos clínicos

Dry eye syndrome is a common disorder provoking changes in tear quantity and composition being the most common ophthalmic manifestation of systemic inflammatory diseases. Untreated dry eye could cause increased risk of ocular infection, corneal ulcer and blindness. Only a few drugs are authorized so far for the treatment of dry eye disease and the possibilities of evolution in this sector are immense. Accordingly, the future tendency is towards the development of drugs to control the inflammation or stimulate the mucin and tear secretion. A significant number of new potential solutions are under development or placed in the pharmaceutical pipeline, promising better results and lesser side effects, but still leaving unattended the main causes of the disease. In this article, we review the corresponding literature, recent clinical trials data and patents concerning future pharmaceutical compounds for dry eye disease treatment, presenting the new strategic movements of the pharmaceutical industry.El síndrome de ojo seco es un trastorno bastante común, provocando cambios en la cantidad y la composición de lágrima, siendo la manifestación oftálmica más común de enfermedades inflamatorias sistémicas. El ojo seco no tratado puede provocar un aumento del riesgo de infección ocular, úlceras corneales y en casos extremos ceguera. Actualmente sólo unos pocos fármacos están autorizados para el tratamiento de la enfermedad y las posibilidades de evolución en este sector son inmensas. La tendencia del futuro está dirigida hacia el desarrollo de fármacos que controlan la inflamación o estimulan la secreción de las mucinas y de las lágrimas. Un número significativo de nuevos compuestos están en desarrollo o ya están en ensayos clínicos, con aparentes mejores resultados y efectos secundarios menos adversos, pero una vez más dejando desatendidas las principales causas de la enfermedad. En este artículo revisamos la literatura correspondiente, los últimos datos de los ensayos clínicos y las patentes relativas a futuros compuestos farmacéuticos para el tratamiento de la enfermedad del ojo seco, desvelando los nuevos movimientos estratégicos de la industria farmacéutica

The role and therapeutic potential of melatonin in age-related ocular diseases

The eye is continuously exposed to solar UV radiation and pollutants, making it prone to oxidative attacks. In fact, oxidative damage is a major cause of age-related ocular diseases including cataract, glaucoma, age-related macular degeneration and diabetic retinopathy. Since the nature of lens cells, trabecular meshwork cells, retinal ganglion cells, retinal pigment epithelial cells and photoreceptors is post-mitotic, autophagy plays a critical role in their cellular homeostasis. In age-related ocular diseases, this process is impaired, thus, oxidative damage becomes irreversible. Other conditions such as low- grade chronic inflammation and angiogenesis also contribute to the development of retinal diseases (glaucoma, age-related macular degeneration and diabetic retinopathy). As melatonin is known to have remarkable qualities such as antioxidant/antinitridergic, mitochondrial protector, autophagy modulator, anti-inflammatory and anti-angiogenic, it can represent a powerful tool to counteract all these diseases. The present review analyzes the role and therapeutic potential of melatonin in age-related ocular diseases, focusing on nitro-oxidative stress, autophagy, inflammation and angiogenesis mechanisms

Ocular Manifestations of Alzheimer’s and Other Neurodegenerative Diseases: The Prospect of the Eye as a Tool for the Early Diagnosis of Alzheimer’s Disease

Dementia, including Alzheimer’s disease (AD), is a major disorder, leading to several ocular manifestations amongst the elderly population. These visual disorders may be due to retinal nerve degenerative changes, including nerve fibre layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. There is no cure for Alzheimer’s, but medicines can slow down the development of many of the classic symptoms, such as loss of memory and communication skills, mood swings, and depression. The disease diagnosis is difficult, and it is only possible through PET scans of the brain, detecting evidence of the accumulation of amyloid and tau. PET is expensive and invasive, requiring the injection of radioactive tracers, which bind with these proteins and glow during scanning. Recently, scientists developed promising eye-scan techniques that may detect Alzheimer’s disease at its earliest stage, before major symptoms appear, leading to improved management of the disease symptoms. In this review, we are discussing the visual abnormalities of Alzheimer’s and other neurodegenerative diseases, focused on ocular functional-visual-structural biomarkers, retinal pathology, and potential novel diagnostic tools

An update on dry eye disease molecular treatment: Advances in drug pipelines

Introduction: Dry eye disease is a common disorder provoking changes in tear film and ocular surface. Untreated dry eye could cause ocular infections, corneal ulcer and blindness. Only a few drugs are authorized so far for the treatment of dry eye disease and the possibilities of evolution in this sector are immense. Consequently, a significant number of new potential solutions are under development or placed in the pharmaceutical pipeline, promising better results and lesser side effects.Areas covered: In this article, the corresponding literature and recent Phase III clinical trial data and the corresponding literature, for dry eye disease treatment are reviewed, revealing the new strategic movements in drug pipelines.Expert opinion: From the clinical trial results, the advancement in tear substitutes and secretagogues in addressing specific deficiencies of tear components even though not resolving the underlying conditions of the disease is evident. The vast majority of new compounds under development are anti-inflammatories, steroids, non-steroids and antibiotics; however, there are also some novel lubricating drops and mucin-tear secretagogues. A future aggressive therapy for dry eye, depending on the severity of the symptoms, would include combinations of soft steroids, anti-inflammatories, such as cyclosporine A, with the addition of the new polyvalent mucin and tear secretagogues