A recent report by PhRMA on US pharmaceutical research companies that were developing new medicines to treat debilitating neurological disorders documented that there were over 500 new compounds in the research pipelines. Neurological disorders such as Alzheimer’s, epilepsy, multiple sclerosis, Parkinson’s, and stroke were the targets for the many research programs.
The medicines in development (either in human clinical trials or at the Food and Drug Administration awaiting approval) included:
- 171 medicines for pain
- 82 medicines for Alzheimer’s disease
- 58 medicines for brain tumors
- 46 medicines for multiple sclerosis
- 30 medicines for Parkinson’s disease
- 29 medicines for migraine
- 26 medicines for epilepsy
- 23 medicines for stroke
Other medicines in development targeted brain injuries, Huntington’s disease, ALS, spinal cord injury, myasthenia gravis, juvenile cerebral palsy, and restless legs syndrome. The majority of the promising new drugs in development work by new and complex mechanisms which require demonstration (“proof of concept”) that the drug will behave in humans the same as it did during the experiments in animals.
Since treatment of many on these neurological disorders requires that the drug penetrates the Central Nervous System (brain and spinal cord) in order to be effective, early clinical trials may require that Cerebral Spinal Fluid (CSF) is sampled. This delicate procedure is needed in order to demonstrate that the drug crosses the blood-brain-barrier or that specific chemical constituents of the CSF (biomarkers) are modified as the dose of the new drug is increased.
WCCT Global has many years of experience in the collection of CSF as a unique study or during the first-in-man single or multiple dose studies. WCCT Global has carried out trials where only one or two lumbar punctures with single CSF sampling were required, as well as trials that required up to 48 hours of serial CSF collection at multiple time points. We work with board-certified anesthesiologists and provide highly trained nursing and medical support throughout the entire study. Sample processing, storage and shipment for analysis can be tailored to the unique requirements of each biomarker and are conducted in a strict GCP environment.
WCCT Global’s on-site treatment room provides a spacious, sterile environment for these critical study procedures, thereby sparing patients and clients the unnecessary scheduling difficulties of a hospital setting. Should a sponsor or particular study protocol require it, WCCT’s anesthesiologists can place the intrathecal catheters utilizing fluoroscopy. During the catherization period and approximately 24 hrs post catheter removal, subjects are required to lie down with limited movement. An example of appropriate activities during this time would include using the restroom and sitting up to eat. This restriction in movement helps to reduce the incidence of spinal headaches and also helps to maintain good catheter placement.
Reasons for Cerebral Spinal Fluid Sampling
- Proof of CNS penetration
- CSF PK assessment
- CSF Biomarker evaluation
- Blood/CSF Drug/Biomarker PK/PD modeling
WCCT Global has worked closely with sponsors and our IRBs to ensure that subject safety and comfort is paramount and therefore has been able to successfully recruit a variety of volunteers for these trials. WCCT has recruited healthy young volunteers, healthy elderly volunteers, and healthy Japanese volunteers into a number of trials requiring CSF sampling.
The PK/PD relationship (plasma and CSF) of Arbaclofen, the R-enantiomer of the GABAb agonist, baclofen, has been evaluated at WCCT Global. It was determined that the SCF penetration of the r-enantiomer (Arbaclofen) of baclofen at clinically relevant plasma concentrations was not associated with sedation. The ability to document CSF penetration of the active enantiomer and the absence of sedation is a very strong indication that Arbaclofen will not cause sedation during routine use in patients.