Highlights of CHDI

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The 12th Annual CHDI HD Therapeutics Conference was held in St. Julian’s, Malta, April 24–27, 2017.

By: Nicholas Caron, PhD

The 12th Annual CHDI HD Therapeutics Conference in the town of St. Julian’s, Malta, welcomed scientists from academia and industry to present data and discuss current research aimed at treating HD. The conference opened with a powerful and inspirational keynote speech from the Miner/Mulligan/Colerdark/Johnson family, who discussed the impact that HD has had on their lives over the past two years since the mother and two of three daughters were diagnosed with HD.

The first scientific session, chaired by Dr. Jim Rosinski (CHDI) and Dr. Lesley Jones (Cardiff University), focused on the utility of unbiased systems approaches to studying HD. Dr. Jones and Dr. Davina Hensman Moss (UCL) presented work implicating DNA damage/repair response genes as key genetic modifiers of HD onset and progression. Dr. Chris Kay (UBC) discussed haplotypes associated with the CAG expansion mutation and how these can be used for allele-specific silencing of the mHTT gene in different HD populations.

The next session, chaired by Dr. Matt Lee (CHDI) and Dr. Marcy MacDonald (MGH), shifted focus to HTT structure and function. Dr. Kevin Weeks (UNC) presented work on novel technology to determine the structure of HTT mRNA and to design small molecule therapeutics against mHTT-specific RNA structures to achieve allele-specific silencing. Dr. Albert Ruzo (The Rockefeller University) presented work showing novel developmental phenotypes present in HD compared to isogenic control human embryonic stem cells (hESCs).

The next scientific session, chaired by Dr. Andrew Howard (CHDI) and Dr. Edward Wild (UCL), shifted focus toward HTT-lowering therapeutic approaches for HD. Dr. Wild presented compelling data implicating neurofilament light chain levels in the CSF and plasma as reliable biomarkers of HD progression. Dr. Nicole Déglon (Lausanne University Hospital) spoke of her work using a novel self-inactivating CRISPR/Cas9 system to suppress HTT both in vitro and in vivo.

The next session, chaired by Dr. Roger Cachope (CHDI) and Dr. Andrew Leuchter (UCLA), focused on the role of neuronal dysfunction in HD. Dr. Joseph Cheer (University of Maryland School of Medicine) spoke of the impairment of the endocannabinoid system in HD patients, and the potential benefit of endocannabinoid-based therapies for treating the psychiatric symptoms of HD. Dr. Abdellatif Benraiss (University of Rochester) presented exciting work using virally expressed brain-derived neurotrophic factor (BDNF) and noggin to promote mobilization of endogenous neural stem cells to replace striatal medium spiny neurons (MSNs) as a potential disease-modifying therapy for HD.

The final scientific session was chaired by Dr. Rebecca Fuller (CHDI) and Dr. Francisco Cardoso (University of Minas Gerais), and examined emerging opportunities for HD therapies. Dr. Anne Rosse (Cardiff University) presented the current status of cell-replacement therapy for HD via transplantation of hESC-derived MSNs. Dr. Andrew Yoo (Washington University School of Medicine) presented some of his group’s work using micro RNAs along with growth factors, for direct neuronal reprogramming of HD patient somatic cells to model HD.

This year’s CHDI conference saw major advances in our understanding of genetic modifiers on the course of HD; novel therapeutic approaches to target HTT at the DNA, RNA, and protein level; new biomarkers to assess disease onset and progression; and strategies to promote survival of vital neural pathways as well as to replace neurons that have degenerated as part of the disease, among other notable research. Together, the unrelenting efforts of the HD scientific community continue to push us closer to treating this devastating disease.

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