KGI Helping Darvish Brothers Find Cure for Muscle-wasting Disease
Dr. Daniel Darvish is two steps closer to finding a cure for the muscle-wasting rare disorder that is gradually robbing him and his brother of their ability to live healthy and productive lives.
Darvish was notified recently that both of the orphan drug designation applications he filed in February at a workshop hosted by KGI's Center for Rare Disease Therapies had been approved by the U.S. Food and Drug Administration.
"It's a significant boost to our efforts, both in terms of fund raising and partnering with pharmaceutical companies specializing in clinical development of orphan drug products," said Darvish, who suffers from Hereditary Inclusion Body Myopathy, or HIBM.
The approval cemented a relationship between the Darvishes and KGI to help determine if the drug therapy that was approved is successful.
Ian Phillips, KGI's Norris Professor of Applied Life Sciences and director of the Center for Rare Disease Therapies, said Professors Jim Osborne and Craig Adams, director and assistant director, respectively, of the KGI Center for Biomarker Research, will be starting a study in hopes of finding a biomarker for HIBM.
"If Daniel gets the treatment that was designated by the FDA for an orphan drug, he will need a blood test to see that the treatment is working," Phillips said.
The collaboration between KGI and the Darvishes is mentioned in a video that has been shown at HIBM fundraisers across the nation.
Unlike other patient advocates who attended the workshop to learn how to prepare and file an orphan drug designation application, Darvish is racing against time not only for others but for himself.
Daniel Darvish and his brother, Babak, are both medical doctors who have HIBM, a progressive and muscle-wasting disorder caused by a mutant gene that impairs the body's ability to produce sialic acid, a vital sugar implicated in muscle and kidney function.
Symptoms of the disease usually begin in a person's twenties and typically lead to total disability in 10 to 15 years. There are only about 500 known cases worldwide.
The Darvishes were both in medical school when their symptoms started. Babak Darvish, Daniel's younger brother, noticed weakness in his fingers that made it difficult to play his guitar and climb stairs. Soon after, Daniel developed similar symptoms.
Only a few scientists were studying HIBM at the time, so Darvish realized that the only way to speed up the research was to actively become involved and attempt to increase the number of research groups working on the disease.
In 1997, the Darvishes cofounded Advancement of Research for Myopathies (ARM), a non-profit organization dedicated to raising funds for HIBM research. Several years later, they established HIBM Research Group (HRG), a non-profit molecular laboratory dedicated to advancing HIBM research by producing needed biomaterials. The lab, accredited by Clinical Laboratory Improvement Amendments (CLIA) and the College of American Pathologists (CAP), performs genetic testing for HIBM and acts as a clearinghouse for HIBM specific biomaterials (a concept similar to biobanking).
Phillips visited HRG before the February workshop, and "was enormously impressed with the fact that [Daniel Darvish] was researching his own disease and trying to come up with a cure." Phillips added: "Time is a factor for him."
"It was a huge spiritual uplift that he came to the workshop, submitted his orphan drug designation applications and both were approved," said Phillips.
During the workshop, officials from the FDA met with patient advocates like Darvish as well as pharmaceutical and biotech company representatives to walk them through the orphan drug product designation application process. The purpose was to promote the development of drug therapies for people who are suffering from rare diseases, which is the core mission of KGI's Center for Rare Disease Therapies.
When asked what he learned from the workshop, Darvish said, "That contrary to popular rumors, it is possible to do it. All you need is a 'burning desire,' good scientific rational and information, and a little bit of funding."
To receive orphan designation, the proposed drug therapy must target a rare disease (one with a patient population of 200,000 or less) and it must show promise for treating the rare disease.
One of Darvish's applications was for ManNAc (N-Acetylneuraminate), a sialic acid biosynthesis pathway intermediate, a simple sugar made by almost all cells in the human body. The muscles of HIBM patients do not make enough ManNAc. Studies on mice have shown that ManNAc, when given orally, can slow or stop the disease's progression, Darvish said.
"All data to date seems to indicate ManNAc is not only safe, but potentially beneficial, even during pregnancy," Darvish said. "However, this needs to be tested and confirmed in human patients."
The second application was for a gene therapy vector to replace the mutant gene and cure the disease.
Darvish said the Orphan Drug Act of 1983 gives companies specific financial and exclusivity incentives to develop drugs for rare disorders.
"Now that we have orphan drug status, we will be able to take advantage of these benefits," Darvish said.
The next step will be to apply to the FDA for an Investigational New Drug (IND) and begin early phase clinical trials.
"We hope that the trial will begin in one to three years depending on the outcome of animal toxicology studies that will begin soon," Darvish said.
By Elaine Regus