Discovering a disease-modifying therapy for intractable ailments such as Alzheimer’s, Parkinson’s and Huntington’s diseasehas long been considered the holy grail of central nervous system (CNS) research and drug development. Symptommanagement is the only therapy currently available for many suffering from these and CNS disorders for which we have not yet found a cure.
One of the biggest challenges in the development of a successful CNS compound is finding a way to get the drug across the blood-brain barrier (BBB). If we can get a compound into the brain, we then have to figure out how to get sufficient amounts into the brain without delivering so much drug to the body that systemic toxicity is an issue. If biomaterials such as lisosomes and polymeric nanoparticles (Nature; September 2009) could be used to facilitate efficient transport across the BBB (creating a 1:1 ratio of brain-to-plasma drug levels rather than, say, a 1:10 ratio), we could potentially give less drug and yet see more in the brain. Dose-limiting toxicity might not be such an obstacle if we could see the desiredpharmacodynamic effect with lower levels of drug circulating in the body.
But even disease modification is usually defined as slowing the rate of decline or the rate of progression of symptoms. What if we could not only change the course of the disease, but what if we could actually restore previous function? What if further decline was not inevitable? In addition to serving as drug delivery vehicles, biomaterials can be used to deliver other therapeutic agents (trophic agents and growth factors, e.g.) and even genetically modified cells directly to effected areas. Imagine the possibilities if we could stimulate the regrowth of dopaminergic neurons in Parkinson’s patients while simultaneously protecting the functioning neurons. NsGene has successfully implanted its encapsulated cell biodelivery product (NsG0202) into 6 patients with Alzheimer’s disease.
So many of us are in the race to develop the next blockbuster CNS drug, that we may be missing the mark. Perhaps the solution is more bio, less tech. Biomaterials may be the missing piece in the massive efforts being put forth by big pharmato cure the incurable. I say, forget symptom management. In fact, forget disease modification. Let’s focus on getting back to baseline. Optimistic? Naïve? Maybe. But if we if we shoot for the stars we just might hit the moon.