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Gene therapy holds great promise for neurological diseases. While it’s notoriously difficult to deliver drugs across the blood-brain barrier, advances in gene therapy vectors and targeted promoters are allowing researchers to deliver molecular treatments to the brain more efficiently than ever.
Solving a complex neurological problem in the laboratory is just the beginning of producing a successful gene therapy. Before a gene therapy can become a lifesaving treatment, it must pass rigorous safety and efficacy testing to determine that it’s appropriate for humans to use.
Refining the delivery method so that the desired gene reaches the right part of the brain in the right amounts can be especially challenging in larger animals that are the key to obtaining data that translates to the clinic.
Choosing to work with a seasoned research partner like Charles River Laboratories provides access to decades of experience at every step of the process. Once the delivery vector has been perfected, it must be tested in both small and large animals. These tests will measure how far the gene product distributes through the brain, determine whether an improvement in symptoms requires delivery to a specific brain structure, and establish the maximum dose that’s safe for humans.
“Our clients usually know exactly what they want, but they don’t know if it’s possible,” said Enrique Garea Rodriguez, PhD, head of study directors at Charles River’s site in Göttingen, Germany. “We can run studies with different scenarios, so they have a better feeling how their component will work in the clinical situation.”
Charles River’s neuroscience group combines a unique blend of expertise with a variety of neurological, neurodegenerative, and psychiatric diseases, custom animal models, and robust translational technologies like noninvasive multispecies neuroimaging that mirrors what’s used in the clinic.
In a clinical setting, doctors typically use neuroimaging techniques including MRI, PET, and CT to diagnose patients and study their disease progression. Charles River has led the field in applying these imaging techniques to animals in preclinical studies. Because taking samples from the brain causes damage, imaging tools are critical for understanding both the disease state and the effects of the treatment. By using the same imaging in preclinical work that will be used in human patients, that data can be applied to clinical situations.
“Whether we are looking at efficacy or safety, we are using clinically applicable imaging tools,” said Antti Nurmi, PhD, managing director of Charles River’s site in Kuopio, Finland. “We have excellent ways of ensuring that we can track the product we are delivering, whether in smaller species or larger species, and that these techniques also apply the same way in humans.”
Working with rodents can provide valuable preclinical data, but the formulation may not perform the same in a much larger human brain. “Testing in large animals is one of the most critical steps to see if your first plan, where you have nice data in rodents that works perfectly, is still going to work in humans,” said Dr. Enrique Rodriguez. These tests also offer an opportunity to adjust production parameters to scale production. “Sometimes you have to compromise if you want to produce large volumes that you can apply to many patients later,” he added. “This is the challenging part.”
Charles River delivers safety and efficacy testing services across a global network of facilities that support full programs and specialized assessments in all laboratory animal species. Scientific and regulatory advisors offer insight and guidance to help clients tackle their toughest challenges and reach their goals.
“Some clients have the money, the idea, and the intellectual property, and they outsource everything to CROs to develop the drug,” said Nurmi. “We have some of these clients who start from scratch, but we also have clients who come to us just for the tricky things that they cannot do themselves.”
Learn more about Charles River neuroscience.criver.com.