Drug for multiple sclerosis prevented disease development when tested on animal models

Scientists from the Neurological Sciences Institute at Oregon Health & Science University have shown that an investigative drug for multiple sclerosis and related diseases prevented disease development when tested on animal models.

The drug, LGD5552, prevented rats from developing a well-established animal model of MS. San Diego-based Ligand Pharmaceuticals Inc. collaborated in, and funded, the study. The results are being presented today at Endo 2004, the national meeting of The Endocrine Society in New Orleans, La.

"While there is much more research to be done on this compound, these initial results are very exciting," explained Bruce Bebo Jr. Ph.D., a scientist at NSI and assistant professor of neurology in the OHSU School of Medicine. "LGD5552 is a member of a class of drugs called non-steroidal selective glucocorticoid receptor modulators with very effective, anti-inflammatory properties and a profile of tissue selectivity resulting in limited side-effects when compared to other drugs currently used to treat MS and related diseases."

Bebo and his collaborators studied rats suffering from experimental autoimmune encephalitis, a commonly studied animal model for human MS that has been used for about 50 years. The researchers provided some of the animals with LGD5552 at the time of disease induction. A second group of animals received a related anti-inflammatory called prednisolone. The third group of animals went untreated.

While the untreated animals developed paralysis , prednisolone-treated animals suffered reduced effects and LGD5552-treated animals remained free of weakness. In addition, the LGD5552-treated animals maintained their body weights, while other animals in the study lost weight. Animals that received the test drug also didn't develop inflammatory lesions in the spinal cord as did other animals. These lesions also are common in humans suffering from MS.

"One encouraging prospect of LGD5552 is that our data shows the compound will have reduced side effects," Bebo said. "Current medications available for MS and related disorders can cause high blood pressure, fat metabolism problems and osteoporosis. While additional research needs to be conducted on the orally administered test drug, we believe these commonly witnessed side effects will be reduced. "

"Glucocorticoids have been used to treat MS for decades. Unfortunately, they have lots of side-effects which limit how long you can use them," Said Dennis Bourdette, M.D., chairman of the OHSU Department of Neurology and Director of the MS Center of Oregon. "LGD5552 and related drugs open the possibility of treating MS patients long-term with a glucocorticoid-type drug without all the side-effects. This is a very exciting prospect."

"We are very excited about the data indicating that LGD5552, a non steroidal-glucocorticoid with tissue selective properties, prevents disease development in a model of multiple sclerosis," said Andres-Negro Vilar, M.D., Ph.D., Ligand's executive vice president research and development and chief scientific officer. "In the initial study, designed to assess the potential of the compound for the treatment of multiple sclerosis, LGD5552 showed efficacy equivalent to the current standard of therapy, the steroidal glucocorticoid prednisolone. In addition, our compound showed a more robust response to treatment, as no animals in study developed the disease. In contrast, 25 percent of animals in the prednisolone-treated group presented a blunted disease process in spite of treatment. Since LGD5552 exhibits an improved side effect profile as compared with steroidal glucocorticoids, this new family of compounds may provide novel avenues for more prolonged use of non-steroidal glucocorticoids for the treatment of multiple sclerosis."

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs) and Signal Transducers and Activators of Transcription (STATs). For more information, go to www.ligand.com.

Located on OHSU's West Campus, the Neurological Sciences Institute at OHSU studies nervous and sensory systems using a wide range of techniques from the level of molecules to the level of behaving human beings.