From the Bench- The Labs of Drs. Andrew Stern and Clare Baecher-Allen

We are excited to be expanding our network of ALS researchers and the impactful work being done across our labs at Mass General Brigham. This month, we highlight the contributions of Mass General Brigham neuroscientists Clare Baecher-Allan, PhD, and Andrew Stern, MD, PhD, whose dedication and innovative research are advancing the field of ALS. 

Dr. Andrew Stern is a cognitive and behavioral neurologist at Brigham and Women’s Hospital, where he treats patients with frontotemporal dementia (FTD), primary progressive aphasia (PPA), and other brain diseases that appear different from ALS but share similar underlying molecular mechanisms. 

Dr. Clare Baecher-Allen is an immunologist with extensive experience in human immunology. Her specific expertise includes regulatory T cells (Tregs) and immune dysfunction in diseases such as Multiple Sclerosis, Alzheimer’s Disease, and ALS. 

 
The Stern Lab 
Under the microscope, most people with ALS have abnormal clumps of a protein called TDP-43 in the nerve cells of the spinal cord and brain. Sometimes, the TDP-43 instead forms abnormal clumps in different nerve cells, such as ones that control emotional control, problem-solving, language comprehension, and memory. In this situation, the patient might have frontotemporal dementia (FTD) or primary progressive aphasia (PPA) rather than ALS, but the microscopic changes are similar. Sometimes people develop both FTD and ALS. 

 The Stern laboratory is researching new tests to detect the abnormal clumps of TDP-43 as early as possible so that new treatments could be administered at the first sign of, or even before, neurological symptoms develop. Currently, there is no such specific test. If successful, Dr. Stern’s work could produce a way to more accurately diagnose patients with ALS, FTD, or PPA at the molecular level and enroll them in the right clinical trial at the earliest possible time. He is collaborating with the Healey & AMG Center for ALS and investigators throughout Mass General Brigham and Harvard Medical School. Dr. Stern is eager to take part in discovering ways to diagnose and treat these terrible diseases. 

 
The Baecher-Allan Lab 
The Baecher-Allan Lab is dedicated to understanding how specific immune cells, particularly Regulatory T cells (Tregs), contribute to the progression of ALS. Tregs play a critical role in regulating the immune system, preventing harmful over-activation that can drive neuroinflammation. Dysregulated immune responses are a key factor in ALS, with immune cells trafficking between the blood and the brain, exacerbating disease progression. 

By analyzing blood samples from ALS patients, the lab studies how Treg function changes over time and how it differs from healthy individuals. This work involves isolating highly pure Treg populations and using gene expression and functional assays to uncover disease-associated dysfunction. 

In collaboration with the Healey & AMG Center for ALS, the lab evaluates how different therapies impact Treg function. A key focus is investigating the effects of low-dose IL-2 therapy, which may boost Treg activity. These studies aim to identify ways to restore healthy immune cell function, potentially slowing ALS progression and improving outcomes for patients. 

 

About the Sean M. Healey & AMG Center for ALS at Mass General  
At the Sean M. Healey & AMG Center for ALS at Mass General, we are committed to bringing together a global network of scientists, physicians, nurses, foundations, federal agencies, and people living with ALS, their loved ones, and caregivers to accelerate the pace of ALS therapy discovery and development.  
 
Launched in November 2018, the Healey & AMG Center, under the leadership of Merit Cudkowicz, MD and a Science Advisory Council of international experts, is reimagining how to develop and test the most promising therapies to treat the disease, identify cures and ultimately prevent it.  
 
With dozens of active clinical trials and lab-based research studies in progress right now, we are ushering in a new phase of ALS treatment and care. Together, we will find the cures.