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QPS – A NEUROSCIENCE COMPANY
QPS provides essential preclinical and clinical research services to help pharmaceutical and biotechnology companies around the globe accelerate the discovery and development of drugs to prevent, treat and cure brain diseases, with a special focus on age-related neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease. QPS understands the specific challenges of translation from animal models to human clinical application. Our extensive experience in CNS affords us a clear view of its complexities and its current global clinical study environment. Our direct links with the international scientific community and close relationships with key opinion leaders worldwide, together with our dedicated experts, original strategies and operational transparency, are keys to the effective execution of CNS programs for our clients.
QPS provides a wide range of pharmacological research tools for CNS disorders. Not only do we offer in vitro techniques using cell-free systems for new drug efficacy investigations, but we also offer a wide range of tissue culture methods which allow medium to high through-put screening on neuronal cultures. This process is ideal for investigating the effects of new chemical entities on an already complex system. Depending upon the target indication and the proposed mode of action, we can select the most appropriate tissue culture system, whether it be primary cultures from transgenic rodent models or one of a wide range of commercially available neuronal cell lines. Furthermore, depending upon the research question, we can stably transfect these cell lines with any gene of interest that would enable high through-put screening or allow a more precise assessment of the test substances’ properties.
The blood brain barrier limits the transfer of drugs from the periphery. Identifying drugs to treat CNS diseases necessitates special approaches to drug development. In addition, given the overlap between CNS neuromodulators and peripheral neurotransmitters, specific drug design strategies are required to prevent peripheral side effects. QPS is aware of these additional considerations, providing appropriate tools for optimizing clients’ drug development programs early on. One such tool is in vitro assessment of membrane permeability, which can yield valuable preliminary information about a novel compound’s BBB penetration properties. Various assessment tools are available to determine brain penetration of a compound after peripheral administration including the determination of the brain/blood and brain/plasma concentration ratios, CSF concentrations as a function of time after drug administration, temporal assessment of tissue distribution, including the CNS, using QWBA and localization of compounds in specific regions of the brain, including the target site(s), using micro autoradiography. In addition to using labelled compounds with high resolution histo-morphological techniques, we can also perform localized brain microdialysis to compare a new therapeutic compound’s plasma kinetics with its brain kinetics. We are able to correlate how concentrations of a compound changes in brain interstitial fluid, over time, with simultaneous pharmacodynamic read-outs.
Toxicology & Safety Pharmacology
QPS offers the full range of regulatory toxicology and safety pharmacology studies in any species. We also have access to various transgenic rodent models, to meet regulatory agencies’ criteria for the use of “relevant disease models” in toxicology studies. One such example is APP transgenic mice with cerebral amyloid angiopathy, used to investigate the vascular effects of anti-amyloid compounds, such as the induction of micro bleeds or micro-edema in the brain. This phenomenon has been recorded only in clinical studies with anti-amyloid antibodies. In addition to the whole range of safety pharmacological studies such as the Irwin Screening Battery for CNS evaluation, we can provide more sophisticated behavioral assessments complemented by electrophysiological studies like telemetric EEG recording, as needed.
The tissue kinetics of a CNS drug is crucial: they determine the duration and intensity of its CNS effects. Apart from plasma pharmacokinetics (PKs), mechanisms that govern CNS tissue kinetics include the rate and extent of blood-brain barrier (BBB) transport and the kinetics of processes of distribution and elimination within the brain. Especially important for CNS drugs, CNS tissue PKs may differ significantly from plasma PKs, because BBB transport and brain distribution often do not occur instantaneously or completely. Therefore, CNS tissue PKs should be considered in CNS Drug Development.Assessing CNS tissue PKs is challenging, since the brain is not a homogeneous tissue, but rather, is composed of many anatomic structures with differing characteristics. In general, the main compartments are: brain extracellular fluid (ECF), brain intracellular space, and cerebrospinal fluid (CSF).
The use of established and new biomarkers can certainly help measure drug activity and toxicity at early stages of clinical development. It can also help identify specific patient populations for clinical study enrolment, determine patient stratification for dosing or follow drug effects when other measures are difficult or not sensitive enough to detect treatment-induced changes. In such cases, biomarkers can become surrogate markers for the drug effect. Ideally, a biomarker for a particular disease has a counterpart in animal models, which on the one hand increases the models’ predictive value and on the other hand, allows direct translation to clinical application.CNS disease biomarkers are quite variable. They can be quantifiable molecules such as proteins, peptides and lipids. They can also be inherited variations of genes (genetic polymorphisms) or even imaging variables. CNS disease biomarkers are often molecules-mainly proteins or peptides, but sometimes, lipids - that can be analysed in CSF or, better yet, in blood samples. However, biomarkers can also be imaging variables. QPS has long-standing experience monitoring a range of CNS biomarkers, based on well-validated protocols
Early Stage Clinical
QPS has built up ample experience in performing CNS drug studies. Over the past decade, we have performed hundreds of Phase I and Phase IIa studies involving CNS compounds. In the early stages of CNS drug development, the delivery of potential therapeutics and their actions are often studied in healthy individuals with normal neurocircuitry. Non-invasive imaging technologies such as nuclear molecular imaging, positron-emission tomography (PET) and single-photon-emission computed tomography (SPECT), functional and structural imaging, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy, electroencephalogram (EEG), event-related potentials (ERPs), polysomnography (PSG), pharmacological challenge models, standardized cognition testing, pupillometry, CSF sampling and proof of biochemical mechanism (laboratory biomarkers) can all be used to create baselines for the study of disease states and their therapeutic modulation - the holy grail: targeted CNS therapy.
Late Phase Clinical
The global reach of QPS clinical research services enables the company to support worldwide clinical trials, integrating experienced sites, all with proven records of reliable and fast patient recruitment. Detailed knowledge of country-specific standards of care also informs site selection for each investigation. So far, QPS has enrolled several thousand patients into AD trials, using the most recent protocols for prodromal Alzheimer’s disease, as well as selecting for moderate to severe disease. Our close relationship with key opinion leaders worldwide allows QPS to support our clients with the most current scientific thinking. Of course, QPS possesses similar knowledge of other CNS diseases, such as Parkinson’s, ischemic stroke and traumatic brain injury. The QPS Neuroscience Team of experienced project managers and competent CRAs delivers seamless customer support from the early stages of clinical trial planning through site selection, investigator training, study initiation, and ongoing monitoring and quality control. Our team is highly conversant with the global regulatory environment; so far, all of our CTAs have been successfully approved by competent authorities as well as by ethical committees/IRBs.
QPS – A Neuroscience Company
The major imperative of drug development is to translate insights gained from basic research into new medications. This task is toughest for CNS therapies. Compared with non-CNS drugs, CNS drugs take longer to reach the market and are subject to greater attrition. These difficulties arise principally because of the complexity of the human brain (the cause of many brain disorders remains unknown), the liability of CNS drugs to cause CNS side effects (which limits their use) and the necessity for CNS medicines to cross the BBB. QPS’ experience and expertise in every stage of CNS drug development, from early preclinical to clinical, enable us to navigate our clients toward successful and timely approval of their CNS therapeutics, whether these are small molecules, biologics or medical devices.