Why neuroprotective agents work in animal models and not in patients
| Stage of Research | Pitfalls |
|---|---|
| Experimental trials | Therapies are not tested by multiple investigators with different stroke models. |
| In experimental trials, outcomes focus on disease and are evaluated early after injury, whereas late, behavioral measures are used in clinical investigations. | |
| Translational problems | Drug doses used in experimental models produce adverse side effects in patients. |
| The therapeutic window is too small to be feasibly applied to most patients. | |
| Therapies are targeted to pathologic mechanisms identified in animal models but not in many patients. | |
| Whereas experimental animals are bred for genetic homogeneity, genetic differences among patients may alter their therapeutic response. | |
| Clinical investigations | Patients with different types of stroke (gray vs white matter, large vs small vessel) are combined in the same study, and therapies may work on one stroke type but not the other. |
| Outcome measures are not standardized, sensitive, or well defined. | |
| Some therapies may be influenced by sex, age, and other individual differences. |