Líneas de investigación/Research lines
The “Instituto Fundación Teófilo Hernando” (IFTH) is an Integral University Centre for Drug Discovery and Development. As this is a wide and multidisciplinary activity, so are our research lines and the expertise of our scientists. Research lines are summarized as follows; to know more about them, please have a look to the biographical sketches of scientists.
1. Pharmacological neuroprotection
About 20 years ago, research efforts at IFTH focused on newly synthesized compounds with potential neuroprotective properties. The concept of neuroprotection is based on the observation that various diseases of the central nervous system (CNS) are accompanied by the loss of different subtypes of neurons. Some times this loss exhibits a sort of selectivity namely, cholinergic neurons in Alzheimer’s disease, dopaminergic neurons in Parkinson’s disease and Huntington’s disease, or motoneurons in amyotrophic lateral sclerosis. In retinal neurodegeneration, several subtypes of cells are also involved. Other disorders are associated to the acute loss of entire brain regions such as stroke or cerebral/spinal cord injury. And some others, have an autoimmune background with myelin loss, as the case is for multiple sclerosis. And still others are originated by nerve lesions, thus causing a highly disabling neuropathic pain.
In the search for therapies for those CNS diseases, for the last two decades, strong focus has been addressed to develop drugs that target specific neurotransmitters, their receptors and transporters; also, the aggregation of pathological proteins that are selective for different neurodegenerative diseases and are believed to cause synaptic deficits have also been targeted. In most cases, the impressive investment and efforts have provided negative outcomes in clinical trials. Thus, new approaches are badly required.
In neurodegenerative diseases, neuroprotection focus on the rescue of vulnerable neurons to delay the appearance of clinical symptoms or to delay disease progression once initiated. In acute stroke, cerebral/spine cord injury, or nerve damage, the neuroprotective strategy extends to prevent the expansion of the lesion and to mitigate the neurological squelae. All these diseases have in common various signalling pathogenic pathways namely, neuroinflammation, oxidative stress, and futile mitochondrial calcium cycling; thus, our synthetic strategy at IFTH is to target those pathways. More specifically, medicinal chemists are targeting the transcription factor NfкB, the purinergic receptor P2X7, and the mitochondrial Na+/Ca2+ exchanger. We are also designing compounds with a dual complementary mechanism of action, trying to enhance their potential neuroprotective effects.
2. Neuropharmacology and neurochemistry of ion channels and neurotransmission
This research line deals with calcium signaling and neurotransmitter release. It is approached from physiological and neurochemical points of view; additionally, at IFTH we have historically performed numerous studies on the pharmacological characterization of the various subtypes of neuronal calcium channels, as well sodium and potassium channels.
3. Clinical research
At IFTH, clinical pharmacologists approach the identification of polymorphisms that can alter the pharmacokinetics, pharmacodynamics, and safety of different drugs. We have mainly studied polymorphisms related with antidepressants, analgesics, antipsychotics, antineoplasic, antivirals, antiplatelet, anticoagulants and drugs for psoriasis. We have been looking for those polymorphisms mainly on enzymes, transporters, and receptors.
Another research lines deal with immunopharmacology, the pharmacology of inflammation and liver/gastrointestinal pharmacology.
4. Clinical trials
We have performed about 150 phase I clinical trials, mostly on bioequivalence studies but also on first-in-human compounds. We are also involved in the design, performance and follow up of phase II/III clinical trials, as well as in postmarketing studies.
For further information, please contact Arturo García de Diego at email@example.com