Research at the MGH is interwoven throughout more than 30 departments, centers and units and is conducted with the support and guidance of the MGH Research Institute. The Research Roundup is a monthly series highlighting studies, news and events.

MGH investigators on the cutting edge of ALS research

Lou Gehrig’s disease – or amyotrophic lateral sclerosis (ALS) – is a debilitating neurodegenerative disorder that impacts motor neurons in the brain and the spinal cord. Eventually these nerve cells die, affecting a patient’s ability to move, eat, speak and breathe.

While there is currently no cure for ALS, researchers at the MGH Neurological Clinical Research Institute (NCRI) are taking a team approach to tackling the disease in the hopes of identifying ways to slow or reverse progression.

The team of more than 60 staff members is dedicated to developing, facilitating and conducting multicenter clinical trials in ALS and other neurological diseases. They use a combination of technological applications, brain imaging and genetic insights to advance the development of new ALS treatments and improve clinical trial methodology.

Technological applications

James Berry, MD, MPH, of the NCRI, says speeding up the clinical trial process involves identifying and tracking measurable biological indicators of disease progression, known as biomarkers, at the beginning and end of a trial to gauge a drug’s effectiveness.

He is seeking to identify new biomarkers by integrating mobile technology into his research. Berry and NCRI colleague Sabrina Paganoni, MD, PhD, are using a cellphone app to collect real-time information on ALS patients’ behavior, function and strength. The app tracks a patient’s daily movements, providing insight into behavioral changes which could indicate disease progression.

Berry is working with Jordan Green, PhD, CCC-SLP, a speech language pathologist at the MGH Institute for Health Professions, to use voice recordings to measure and track changes in patients’ speech.

And, Berry and Pagnoni are using technology to improve patient care in the short term. For example, Paganoni is collaborating with Conor Walsh, PhD, from the Wyss Institute at Harvard University, on a wearable robotic glove that can assist patients with basic motor functions, such as helping them open and close their hands.

Brain imaging

New techniques for imaging the brains of ALS patients could also vastly reduce the time and costs required for clinical trials, while also improving the accuracy of study results.

Nazem Atassi, MD, of the NCRI, and his team have developed a new imaging protocol, using an injectable radioactive tracer called PBR28 to measure neuroinflammation in the motor cortex of ALS patients. The motor cortex controls voluntary muscle movements and is the area of the brain most affected by the disease.

The new protocol can reduce the number of patients needed for a clinical trial from 400 to 30, shorten the duration of the trial from one or two years to two or three months, and provide an objective biological measure of treatment effects.

Genetic insights

Although hereditary forms of ALS only account for 10 percent of all cases, Katharine Nicholson, MD, of the NCRI, believes studying these patients may help identify the earliest molecular and clinical signs of the disease.

Nicholson has launched a multicenter study that tracks the first-degree relatives of individuals with a familial form of ALS who do not yet show symptoms of the disease. The overall goal of the study is to gather information that can inform new treatment strategies and timelines for familial ALS, which could include gene therapy treatments designed to stop disease progression.

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