A Potential Game-Changer for Infants with Rare Neurogenetic Diseases

For decades, doctors, researchers and therapists have been limited in disease-specific clinical tools to evaluate function in children with Tay-Sachs, a rare genetic disease caused by the death of nerve cells in the brain and spinal cord. 

But this limitation might be changing, thanks to upcoming research by MGH Institute of Health Professions’ Dr. Elise Townsend and PhD in Rehabilitation Sciences Fellow Dr. Michael Kiefer. 

The duo recently received a two-year grant from the National Tay-Sachs & Allied Diseases Association (NTSAD) to develop a remotely administered disease-specific rating scale that evaluates the status and progression of infants who have Tay-Sachs or Sandhoff disease. The new tool will be called The Infantile GM2 Rating Scale (Tay-Sachs is sometimes referred to as GM2). 

“I think this tool could be a game changer in terms of clinical trials for GM2,” said Townsend, an Associate Professor of Physical Therapy and Associate Director of the PhD in Rehabilitation Sciences program. “Use of a rating scale like the one we will develop will allow more frequent clinical assessment, without the need for families to travel to one of few care centers that provide the kind of specialized care these children need. Designed to be used both in person and through virtual video conferencing, we will be able to connect with families in their homes and evaluate children’s progress as they undergo experimental treatments.”

The research grant is in collaboration with the Center for Rare Neurological Diseases at Massachusetts General Hospital), and the Leukodystrophy Clinic run by Dr. Florian Eichler. 

“Our values align; Drs. Eichler, Kiefer, and I each bring a piece to this partnership that will allow the work to be done, work that none of us would ever be able to do alone,” explained Townsend. “One of the wonderful things about being at the Institute is that we have opportunities for collaboration with world class, Boston-based healthcare clinics for children, including our partners within Mass General Brigham. This study is an example of those collaborations happening in just the way that we envision.”

GM2 gangliosidosis is a rare genetic disorder that destroys nerve cells in the brain and spinal cord, with the most common form of the disease presenting itself in infancy. GM2 is known more commonly as Tay-Sachs/Sandhoff, a debilitating disease that typically manifests during the first three to six months of life. Over the course of the next few years, which is the life expectancy for many of these children, the child fails to develop or loses developmental milestones and muscles weaken. Vision and hearing loss, seizures, and paralysis ensue. 

Meeting a Critical Need

The National Tay-Sachs & Allied Diseases Association (NTSAD), the administrator of the grant, says the development of disease specific rating scales are a critical foundation for clinical drug trials, regulatory approvals, and the evaluation of long-term treatment for other rare pediatric genetic diseases. NTSAD is turning to Townsend and Kiefer to help it meet a key goal - develop a disease specific rating scale for GM2. 

“There is a real need for the development of a simple, yet elegant way to measure physical and developmental abilities in children with rare neurogenetic conditions,” says Townsend. “That includes motor and cognitive skills, social and emotional development, and disease-specific symptoms in this condition that presents somewhat differently than other rare neurogenetic diseases.”

Townsend says this observational tool will be used by experienced clinicians trained to coach caregivers over Zoom as they position and move the child and provide stimuli to elicit behaviors that can then be coded using the rating scale. Coaching may include instructions such as “Place your child down on the floor on a blanket, wearing only a diaper. Place them on their belly so we can see how they control their head. Position yourself at eye level with the child and talk to them. Shake a rattle placed to one side of their head and see how they respond. Now roll them over on their back. Make eye contact, smile and talk to them.”

Data collected from the observational session will be entered into an electronic database. “Essentially, we aim to develop a condition-specific developmental tool,” she says. “We will have an assessment that has been designed specifically for the host of symptoms and issues that we see in this particular rare disease.” 

Remote Access and Assistance

Townsend says there’s a critical need for a remote development tool. “We will be able to assess vulnerable babies in their homes, where they're safe and comfortable and where they can show us the best of what they can do, and it will happen in a much shorter time,” she says. “We need a way to measure that's friendly for families and safe for children. We need a way to assess virtually, and we need to be able to track them frequently over time - whether they're getting standard care or involved in trials of new medications. This new observational tool will let us track and monitor these children much more readily.” 

The duo’s experiences with other rare diseases positioned them well on the need for a remote component. While working on a project involving another rare pediatric condition, Kiefer was flying around the country for home visits. That was costly, both from a financial and time perspective. When the pandemic struck, that travel and the home-based assessments that came with it stopped immediately. 

The remote component will allow clinical researchers to get to know the disease better because they will be able to access children anywhere in the world with internet; because these diseases are quite rare, broad international access is paramount. 

“We want to know: ‘Can the child use their hands and arms? Take weight on their legs? Control their head? Does the child smile and make eye contact?” says Townsend. “They may not have typical language development, but can they babble? Can they vocalize? Can they make their wants, needs, and feelings understood?”

The $139,000 grant will allow Townsend and Kiefer to work with families and expert clinicians to develop a tool that can help track, monitor, and assess infants’ function. As for how the tool will be developed, the duo expects to collaborate with experts at the MGH Institute along with experts throughout the Mass General Brigham system and around the world. 

If the research is successful, Townsend says this development tool could be used with or modified for other rare diseases. “Because there are other children with rare diseases who show similar patterns of behavior, we’re hoping that with candidate drugs for multiple pediatric rare diseases in the pipeline, we’ll be able to translate use over to other rare and severe neurodegenerative disorders in infants,” she says. “Blessedly, there's now new hope for families and children.