New Therapies:
More Than Two Dozen Drugs
Being Eyed as Possible FGSG

Stubborn cases of FSGS, which will not respond to steroids or the few other strong medications nephrologists have been using against the condition, often plunge patients and their families into the depression of hopelessness. “What is new out there?” the patients ask. “What has research brought us?”

A recent federal gathering of experts in FSGS and glomerular disease revealed some new and possibly exciting developments.  The two-day conference included workshops that focused on what scientists call “novel therapies,” drugs that have not yet been used for FSGS but may very well be tried in the future, in some cases, the near future.

“Our workshop group came up with something like 35 medications that have been used in animal models of glomerular disease,” said Jeffrey B. Kopp, M.D., who does research at the National Institute of Diabetes and Digestive and Diseases of the Kidney (NIDDK) in Bethesda, MD.

Many of them have been tested to some degree in humans and some even havebeen approved for human use, but as treatment for conditions other than FSGS, he said. One example: retinoic acids, Vitamin A derivatives which often are used quite successfully in the treatment of acne and other skin problems

Dr. Kopp’s group is expected to soon start aclinical trial of two of the retinoic acids in patients over 18 with Nephrotic Syndrome (leaking kidney filters) and scarring of the glomerulus, a major component of the kidney filter. A trial document (a protocol) notes that even a mild Vitamin A deficiency can result in a decrease in nephrons, the kidneys overall filtering package.

“Although retinoids have not been used in humans to treat kidney diseases, growing literature on studies based on animal models also suggest its efficacy in kidney disease,” says the protocol. (For more information on the trial, call 301-435-5058.)

Dr. Kopp said that animal models “are by no means perfect models of human disease” and some drugs that conquer animal diseases do not work in people.  “Unfortunately, we need humans to step forward and give it a try, even though there may be side effects, to see if this drug can either advance knowledge or help some people, or maybe many people.”

“There are a lot of things out there that could be used and I’m encouraged. All of us want to get going doing it,” said the researcher.

Another category of novel drugs that will be cropping up in human trials are antifibrotic medications, those designed to stop scarring, which in FSGS cases often progresses to the point of kidney destruction. Dr. Kopp said he is drawing up plans for a four-year nationwide trial of 400 patients with a host of chronic kidney diseases. The antifibrotic tested would be pirfenidone.

Also on the antifibrotic trail are Howard Trachtman, MD of Long Island Jewish Medical Center and Debbie Gipson, M.D., of the University of North Carolina at Chapel Hill and two of the  investigators for the nationwide FSGS Clinical Trial (see related story).  If patients coming through FSGS Clinical Trial either do not qualify  or fail to respond to the FSGS Clinical Trial treatment, their may be a separate antifibrotic  trial, Dr. Gipson said.  “We are just beginning a study to define the proper dose and safety of these new agents. This work must be completed before the novel therapy study can begin.”

“People are hopeful about antifibrotics,” she said, because they will be targeted at the “fibrosis (scarring) pathway” that is common to the various types of kidney diseases that lead to kidney failure.

“By the time FSGS patients are ready for a novel therapy, they will have tried and failed corticosteroids, calcineurin inhibitors such as cyclosporin,  CellCept® or or some combination of immunosuppressive agents,” said Dr. Gipson. “Patients with resistant FSGS continue to accumulate the fibrosis in the kidney.” “We are trying to target the scarring pathway to stop or slow  the accumulation of kidney damage. We are open to the idea that perhaps one drug alone will not work, but the proper combination of several may be effective.”

As for the list of novel therapies that researchers were perusing during the workshop, Dr. Gipson said experts are very motivated” to find more options for our patients.

“Some agents on the list of 35 possibilities have not been tested in humans” she said. “Some of the possibilites are approved for use for other diseases. We are encouraged by the support from the NIH to establish the mechanism and begin  testing of novel agents for FSGS.”

(More information about the novel therapies trial will be forthcoming ..)