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MGH ALS 
Research and Multidisciplinary Clinic News
A Message From Merit Cudkowicz, MD, Chief, MGH Neurology


Members of the MGH ALS Multdisciplinary team at the ALS Clinical Trial Guidelines Workshop.

In late March, many of the MGH ALS Multidisciplinary team attended the ALS Clinical Trial Guidelines workshop outside of Washington, DC, sponsored by the NIH, the International Alliance of ALS/MND, and several other ALS foundations.  

Our MGH ALS Multidisciplinary Co-director, James Berry, MD led a session on phase 2 trial designs in ALS, in which I participated.  He did a fantastic job in sharing his knowledge with academics, industry leaders and patients from around the world.  Our clinical research fellow, Harry Banno, MD, also led a session on preclinical models, which was filled with active discourse. Both Harry and James were great leaders! Katie Nicholson, Sabrina Paganoni, Pat Andres, Alex Sherman also were active participants encouraging dialogues on data sharing, improved outcome measures and innovative recruitment and retention strategies. It was wonderful to see so many of our faculty as leaders in ALS therapy development.

The conference centered on consensus building on aims of early development trials, recruitment, inclusion criteria and desired preclinical packaging.  The goal of the conference is to accelerate development of therapies, and have rigorous criteria for moving forward to patients and also from early development stage to later phase 3 trials. A manuscript outlining the consensus from the conference will be published shortly.

- Merit
Ways to Support New Treatments and Cures for ALS

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Your support drives the most compelling science in ALS today-please consider a donation to help us find new treatments and cures for ALS.
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From the Directors

 
Dear Friends,

We hope you are enjoying the onset of the Spring season. We're excited for the warmer weather and to share promising new research updates from both the  MGH ALS Multidisciplinary Clinic and the Neurological Clinical Research Institute (NCRI). These exciting updates include a drug shown to banish muscle cramps in ALS patients, the Answer ALS study, two new imaging clinical trials and a recent ALS Clinical Trials Guidelines workshop.

And while m any of you may be familiar with the clinical care and research that happens within the MGH ALS Multidisciplinary Clinic and the NCRI, you may also be interested to learn what developments are happening throughout our entire ten divisions of Neurology. We're happy to share with you our 2015 Year in Review, showcasing the great work achieved in the past year to fulfill our mission: to provide outstanding clinical care while rapidly discovering new treatments to reduce and eliminate the devastating impact of neurological disorders.
 
Sincerely,
 
Merit Cudkowicz, MD 
Chief of MGH Neurology

James Berry, MD, MPH
Co-Director of the MGH ALS Multidisciplinary Clinic
 
Darlene Sawicki, MSN, NP-BC
Co-Director of the MGH ALS Multidisciplinary Clinic



Mexiletine, a drug already on the market, may assuage the frequent, painful muscle cramps that vex people with amyotrophic lateral sclerosis.   Read the AlzForum coverage of the study authored by MGH investigator Merit Cudkowicz, MD.

We are excited to report that we are a study site for Answer ALS: Individualized Initiative for ALS Discovery and currently recruiting patients.  James Berry, MD, Co-Director of the MGH ALS Multidisciplinary Clinic, is the principal investigator for our site.  The goal of the Answer ALS Study is to create a large repository of cells called induced pluripotent stem cells (iPSC), bio-fluid samples (blood and spinal fluid), and cell lines for ALS gene identification. It will establish a large and critical foundation for new clinical trials, develop new ways to categorize patients in order to ultimately identify specific druggable pathways, and subtype biomarkers and disease pathophysiology to aid, not only in early diagnosis of disease, but also to monitor the efficacy of newly developed treatments. Most importantly, this data will all be publically available with open access to the ALS research community.
 
There are nearly two dozen research entities, approximately 1,000 patients, six clinic sites including, Massachusetts General Hospital, Johns Hopkins, Emory, Washington University, Ohio State and Cedars-Sinai.  That makes this the single largest coordinated ALS research effort in history.
 
 All 1,000 participants will undergo clinical assessments and blood draws at the Screening Visit. They will have the option to complete a lumbar puncture to obtain CSF fluid at any or all visits of their choosing. Follow-up for clinical assessments and blood draws will occur every three months over a 12-month period.
 
As of April 13, 2016 five of the six clinical sites are enrolling with the total enrollment at 90 participants!  If you are a patient interested in participating in this study, please contact Leah Miller at  or 617-724-7398.  

Leveraging Advances in Imaging Technology to Develop New Treatments for ALS

The Mass General ALS Multidisciplinary Clinic is now conducting two phase 2 imaging trials.  Both trials implement an advanced  brain imaging technique called PBR28 positron emission tomography (PET), to measure inflammation in specific brain regions that control movement. The goal of these trials is test the impact of new drugs on  reducing brain inflammation. 

PET imaging is a powerful tool that can detect molecular changes in the brain using different  PET tracers that bind to specific receptors or proteins. The two ALS trials at MGH are implementing this technique using a tracer called PBR28 that binds to active e microglia and astrocytes.  These trials are the first to use molecular PET  imaging to measure drug response in people with ALS.  This technology is poised to accelerate the pace of clinical drug development in ALS. 

Dr. Sabrina Paganoni
Sabrina Pagnoni, MD, PhD
The first trial, RNS60, has enrolled ALS patients from the MGH ALS Multidisciplinary Clinic, as well as other clinics.  RNS60 is the first ALS study that uses PET technology to measure changes in neuroinflammation as a proof of mechanism to detect target engagement.  Participants in the RNS60 study are  treated for several months, with results of the study expected in the summer of 2017.  "It's very exciting to be one of the first ALS trials to use PET imaging as a biomarker to see if the drug can engage its target in the motor cortex area of the brain," says Sabrina Pagnoni, MD, PhD, principal investigator.  "If we see it, it means that the drug has reached the target area and is modulating neuroinflammation."

Nazem Atassi, MD
The second study, MN-166 (Ibudilast) - is a multi center, open-label, proof-of- mechanism study of MN-166 in people with ALS that also implements PBR28 PET as the readout of Ibudilast's biological activity at the target tissue.   "We're looking forward to leveraging imaging data to enhance clinical trials, which we hope will accelerate the development of new treatments for people with ALS," says Nazem Atassi, MD, Principal Investigator for MN-166.

Both trials are based on preclinical studies suggesting these drugs may be effective in reducing neuro-inflammation which is considered one of the mechanisms that cause ALS.

For more information on the RNS60 trial, please visit clinicaltrial.gov, NCT025254471.  For more information on the MN-166 trial, please visit clinicaltrial.gov, NCT02714036.