By Marilyn Downing
Sanjay Bidichandani is the newest member of our FARA Board of Directors. Dr. Bidichandani earned his MBBS from the University of Pune, India and his PhD from the University of Glasgow, Scotland, UK. He completed his post-doc and assistant professorship in Neurology at Baylor College before becoming Professor of Biochemistry, Molecular Biology and Pediatrics at the University of Oklahoma Health Sciences Center, and served as Vice-President for Research at the Muscular Dystrophy Association. He returned recently to the University of Oklahoma to become head of the Section of Genetics, Department of Pediatrics.
Dr. Bidichandani’s father taught him that while it’s important to be clever, it is even more important to work hard and surround oneself with like-minded dedicated people. His father explained that your best chance to encounter “luck” is through a focused and collaborative effort.
Dr. Bidichandani has worked diligently in an effort to find a cure for Friedreich’s ataxia, and he also had some luck early in his career — to be a part of the research group that found the FA gene in late 1995. Dr. Bidichandani excitedly recounts the story of when his research team at Baylor College in Houston, led by Massimo Pandolfo, discovered the triplet repeat expansion on what is now known as the FXN gene, on chromosome 9.
Today, with the genome mapped, this is a much simpler process, but in 1995 the group had to spend a tremendous amount of time manually screening the coding portions of the gene. They were even beginning to question if they were looking at the correct gene. Then, with a hard-to-read southern blot test and Dr. Pandolfo’s persistence, the needle in the haystack was found in the non-coding region of the gene. The problem was a triplet repeat expansion. The protein affected was named frataxin. History was made and Sanjay had been a part of it. Luck? Intelligence? Determined hard work? Dr. Bidichandani would say it was all three.
What does this triplet repeat expansion do and why does it translate to less frataxin? Researchers have found the expansion causes the gene to fold/close up so that it cannot be accessed and the “recipe” for frataxin is not read properly. Put simply, this lack of the frataxin protein causes the disease progression in Friedreich’s ataxia.
Dr. Bidichandani continues his FA research in the field of epigenetics, a quickly growing and fast moving field. Epigenetics is the study of heritable traits that are not in the DNA/gene of interest, in this case the FXN gene, but in traits that surround it or control the expression of the gene. He says FA researchers are “surfing the epigenetic wave” and applying what’s being learned to FA research. Dr. Bidichandani finds there are continued challenges as they discover that the epigenetic defect in FA can actually turn off/silence expression of the gene. Also, mouse models show that the genetic defect is not static but expands in the dorsal root ganglia and the cerebellum. However, Dr. Bidichandani states, bringing patient frataxin levels to half the normal level — even a quarter of the normal level — will make a huge difference in their lives.
Notably, while at Baylor, Dr. Bidichandani was involved with the discovery of the G130V mutation in Friedreich’s ataxia, after studying the Ramsey family, which presented with a milder form of FA. He finds it remarkable that he now is sitting on the FARA board with Ed Ramsey as chairman.
Dr. Bidichandani attributes much of the growth in FA research to FARA, due to the efforts to collaborate with/between scientists, develop relationships with the pharmaceutical industry, the FA rating scales, the patient registry, and the drive to move projects along. He feels FARA has made those with FA feel a true community. He senses this major partnership between scientists and this FA community motivates the scientists to do their best.
What does Dr. Bidichandani think are the two most exciting advances in FA research in 2013? He says without hesitation the completion of the first phase of the HDAC inhibitor trial in Italy. This trial showed a signal that frataxin could be raised in people through this approach — a significant milestone since the founding of the gene 18 years ago. Going forward we can hope for a U.S. trial of perhaps an even better HDAC molecule. Secondly, he notes the involvement of larger pharmaceutical companies, which is new within rare diseases. One very encouraging example is a recent meeting with Pfizer in which experts attended from different disciplines within the company that were well versed in FA— a truly collaborative exchange and a strong interest in the FA program. Having corporations such as this come to the table offers additional resources for FA research.
This writer would like to say that Dr. Bidichandani is not only a brilliant scientist, but a kind and gentle man. There is no question that the FA community was lucky when Dr. Bidichandani chose this field of research. With such hard work, good people and perhaps a little luck, we will be brought to our next milestone of an approved treatment.