By: Francesca Cicchetti, PhD
This year’s 10th annual CHDI HD Therapeutics Conference, held February 23–26, 2015 in Palm Springs, California, brought together over a hundred researchers from academia and the private sector. The four-day meeting offered an exciting program covering a wide variety of topics related to HD research, from new methodologies to tackle fundamental biological questions, to an entire session dedicated to novel therapies targeting mHTT levels. The presentation of this novel science was accompanied by two significant and memorable events that were highly inspirational to all who attended the meeting. The first was the keynote presentation by Jeff Carroll, who shared his personal HD story. Subsequently, attendees were invited to view an extraordinary documentary called, “The Lion’s Mouth Opens,” made by independent filmmaker Lucy Walker. The film follows Marianna Palka, herself a filmmaker, through her journey of being tested for HD and learning that she is a gene carrier.
The meeting kicked off with presentations by Dr. Robert Pacifici, Chief Scientific Officer, and Dr. Cheryl Fitzer-Attas, Vice President of Clinical Research at CHDI. Together, the speakers gave an account of the research that CHDI has sponsored, current and future programs emerging from their various initiatives and collaborations, and the platforms that have been made available through their various endeavors.
In a session titled “Illuminating HD biology and a next generation of therapeutic interventions,” Dr. Hong-Wei Dong presented his remarkable work decrypting complex brain connections using computational and microscopy approaches. Dr. Myriam Heiman described a new technique referred to as “SLIC,” with which her laboratory studies the function of individual genes in living animals. They are working to determine why some brain cells are more vulnerable than others in HD. The work of Dr. Juan Botas on HD Drosophila, which they breed with various fruit fly species characterized by other genetic mutations, is helping isolate changes and responses that are truly HD-specific. Dr. Jong-Min Lee outlined his work on genetic modifiers.
Industry leaders described novel mHTT-lowering therapies. Dr. George McAllister, Senior Director, Biology at BioFocus, presented a session on his company’s efforts to screen a vast number of chemicals to identify those that show promise in reducing the expression of mHTT. Dr. Lisa Stanek from Genzyme presented their small interfering RNA approach to mHTT lowering, while Dr. Frank Bennett of Isis Pharmaceuticals presented their antisense oligonucleotide approach. Dr. Geoff Nichol of Sangamo Biosciences gave an update on the use of zinc finger proteins and planned clinical trials. The session concluded with CHDI’s Dr. Douglas Macdonald, who described their efforts to identify biomarkers related to HTT silencing.
The last day of the meeting was dedicated to clinical research. Dr. Gilbert Di Paolo presented his work on specific lipids identified in the blood of participants in the TRACK-HD study. Dr. Edward Wild described his work with cerebrospinal fluid biomarkers, showing a positive correlation between mHTT levels in CSF and HD clinical progression. Dr. Michal Geva from Teva gave an update on their ongoing trials, including the PRIDE-HD and the LEGATO-HD trials.
Dr. Sarah Tabrizi summarized her group’s findings in the TRACKOn-HD study. Using cerebral imaging, the group identified striking compensatory mechanisms that take place in the brains of HD patients years before symptoms develop. They are currently exploring the use of neurofeedback techniques that aim to train patients to modify their brain activity to improve performance. Dr. Marios Politis presented on his work on PET imaging, investigating overlapping brain networks involved in HD. Finally, Drs. Ray Dorsey and Bernhard Landwehrmeyer reviewed recently halted, ongoing, and future clinical trials.
Among the highlights of this 10th meeting, attendees had the privilege to hear featured speaker Dr. Story Landis, former director of the National Institute of Neurological Disorders and Stroke. The meeting concluded on an entertaining note with a lighthearted award ceremony.