Massachusetts General Hospital

Basic Science Research

A major focus of Dr. Steve Hersch’s research is to understand the role of the huntingtin protein in the pathogenesis of Huntington’s disease.  

The recipient of federal government grants, Dr. Hersch is also supported by private foundations including the HDSA and the Hereditary Disease Foundation (HDF).Clinical ResearchDr. Hersch and collaborators conduct clinical research studies and clinical trials to advance the diagnosis and treatment of Huntington’s disease.  

He is developing a translational research program to more rapidly bring research findings into clinical practice. 

Dr. Hersch has had leadership roles in Huntington Study Group (HSG) research as well as in    [name of projects at Mass General and/or Brigham, or Harvard.]

Principal Investigator

Steven M. Hersch, MD, PhD

• Professor of Neurology, Harvard Medical School
• Associate in Neurology, Massachusetts General Hospital
• Director, Hersch Laboratory

Research Interests: The role of huntingtin protein in the pathogenesis of Huntington’s disease, development of potential therapeutic compounds, clinical research studies and clinical trials.

Research Techniques: Transgenic mouse models, brain imaging, blood biomarker measures

Diseases Studied: Huntington's disease and other neurodegenerative diseases

Research Scientists

• Chopra, Vanita - Instructor
• Kumaraswamy, Lakshmi Narayanan - Post Doc. Fellow
• Moscovitch-Lopatin, Miriam, PhD, PMP - Instructor

Research Assistants & Technicians

• Khanna, Prarthana- Technician
• Vollor, Lorraine (Raine) - Technician
• Goodman, Rachel - Technician
• Pashos, Nicholas - Technician
• Sittampalli, Balamani

Updated 3/30/2012

Basic Science ResearchThe Hersch Laboratory is currently conducting research in the following areas.

•    Neuroanatomic and chemical changes
•    The huntingtin protein
•    Animal and cell models
•    Experimental treatments
•    Brain imaging
•    Genetic modifiers of HD
•    Alterations in gene and protein expression and function
•    Biomarker developmentClinical Trials

Creatine, Tolerability, and Efficacy in Huntington's Disease (CREST-E)

This study, a definitive test of whether high- dose creatine can slow the progression of HD, is in collaboration with the Huntington’s Study Group and funded by the National Institutes of Health, the National Center for Complementary and Alternative Medicine (NCCAM) and the U.S. Food and Drug Administration (FDA) Orphan Products division.

Creatine is a natural substance that can help supply energy to cells and also reduces oxidative stress to brain cells. In HD, brain cells run out of energy, hastening their degeneration. Earlier studies using creatine with HD mouse models as well as smaller pilot clinical trials led by Drs. Hersch and Rosas demonstrated impressive results. “Large amounts of creatine have to be ingested in order for therapeutic levels to reach the brain, so safety was a big concern,” says Dr. Hersch. “However, our Phase II trial with only 10 patients showed that high levels were safe and reached the brain.We were also amazed to see that a blood biomarker that detects brain degeneration was normalized, and brain imaging showed a slowing of brain shrinkage.”

Now, 650 patients from 44 sites around the world will test whether creatine monohydrate can slow the progression of HD in comparison to a placebo. The trial will take five years and millions of dollars to determine whether the biological effects that were observed in the small trial will translate to significantly slowing down disease progression and maintaining the quality of life for patients with HD.

To find out more about this trial visit the study description on the Partners Clinical Research Network (CRnet).

NCBI PubMed publications

1. Altered white matter microstructure in the corpus callosum in Huntington's disease: Implications for cortical "disconnection"  Rosas HD, Lee SY, Bender A, Zaleta AK, Vangel M, Yu P, Fischl B, Pappu V, Cha JH, Salat DH, Hersch SM.  Neuroimage. 2009 Oct 19. [Epub ahead of print]
2. Single-step detection of mutant huntingtin in animal and human tissues: a bioassay for Huntington's disease. Weiss A, Abramowski D, Bibel M, Bodner R, Chopra V, DiFiglia M, Fox J, Kegel K, Klein C, Grueninger S, Hersch S, Housman D, Régulier E, Rosas HD, Stefani M, Zeitlin S, Bilbe G, Paganetti P.  Anal Biochem. 2009 Dec 1;395(1):8-15. Epub 2009 Aug 6.
3. Complexity and heterogeneity: what drives the ever-changing brain in Huntington's disease? Rosas HD, Salat DH, Lee SY, Zaleta AK, Hevelone N, Hersch SM. Ann N Y Acad Sci. 2008 Dec;1147:196-205. Review.
4. Repeat instability in the 27-39 CAG range of the HD gene in the Venezuelan kindreds: Counseling implications.
   Brocklebank D, Gayán J, Andresen JM, Roberts SA, Young AB, Snodgrass SR, Penney JB, Ramos-Arroyo MA, Cha JJ, Rosas HD, Hersch SM, Feigin A, Cherny SS, Wexler NS, Housman DE, Cardon LR; International-Venezuela Collaborative Research Group. Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):425-9.
5. Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity.  Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B, Greve D, Hevelone N, Hersch SM. Brain. 2008 Apr;131(Pt 4):1057-68. Epub 2008 Mar 12.

MassGeneral Institute for Neurodegenerative Disease

Phone: 617-726-1278
Fax: 617-724-1480
Email: mghmind@partners.org

Public Transportation Access: yes
Disabled Access: yes

How to Apply for Positions

How to apply for jobs: Send an e-mail to mghmind-jobs@partners.org to receive an automated e-mail with full instructions for all types of positions.

Fundraising Contact

Contact Shawn Fitzgibbons in the Mass General Development office at 617-643-0447 or sfitzgibbons@partners.org.

Administration

Anne B. Young, MD, PhD
Director, Massgeneral Institute for Neurodegenerative Disease 
Professor of Neurology, Harvard Medical School

Directions to MIND Research labs (PDF)

Clinical Appointments, Consultations & Clinical Trials

ALS (Amyotrophic Lateral Sclerosis) Multidisciplinary Clinic
Phone: 617-724-3914

Dystonia Clinic
Phone:  617-643-6997

Frontotemporal Disorders Unit
Phone: 617-726-1728

Huntington's Disease Clinic
Phone: 617-724-9234

Memory Disorders Unit
Phone: 617-726-1728
Alzheimers, Dementia with Lewy Bodys, Frontotemporal dementia, Pick's Disease

Movement Disorders Unit
Phone: 617-726-5532
Dystonia, Huntingtons, Parkinsons

Parkinson Disease and Movement Disorders Clinic
Phone: 617-726-5532