Lauren Elman, MD, remembers learning about polio in medical school. “There were pictures of people in iron lungs in our textbooks, and I was fascinated but so grateful to live in a world where this was largely a historical phenomenon,” she says. “It makes me wonder what disease medical students will have a similar reaction to 50 years from now.”
As Director of Clinical Research for Penn Medicine’s Comprehensive ALS Center and Director of Penn’s Muscular Dystrophy Association (MDA) Clinic, she has a few ideas.
“One thing that is on the way for spinal muscular atrophy (SMA) and potentially other neuromuscular diseases is gene therapy,” Dr. Elman says. “This could transform the way these diseases are treated and lead future generations of clinicians to look back on them much as I looked back on polio.”
Discovering Progress through Biomarkers
That future is approaching more rapidly than some might think. Penn Neurology is actively involved in a number of pre-clinical projects in this area, including a significant amount of biomarker work.
“Researchers are working aggressively on SMA, Kennedy’s disease and ALS quantitative imaging biomarkers,” she says. “Because gene therapy trials typically enroll very small numbers of patients – sometimes six to 10 people with no placebo group – you need very sensitive quantitative biomarkers to meet outcomes and determine efficacy. At Penn, we’re exploring novel biomarker outcomes to move that forward and help with clinical trial design.”
Much of this work falls under the banners of the Penn Comprehensive ALS Center, which was created in 1999 to care for people with this life-altering disease, and Penn’s MDA Center, which has been serving the community since the early 1970s. The centers, with a caseload of hundreds of patients, bring together specialists from a wide variety of fields, including neurology, genetics, nursing, pulmonology, cardiology, endocrinology, physical and occupational therapy, speech and language pathology, and nutrition.
Research plays a prominent role with regular partnerships on projects with Penn specialists in the areas of neuroradiology, neuropathology and neurogenetics. There are currently five active clinical trials for adults with ALS and other neuromuscular diseases, and other opportunities to participate in research as well.
Reinventing the History of Spinal Muscular Atrophy
“Some of the things we’re able to offer patients today were science fiction when I was in training,” says Dr. Elman. “For example, most adult patients with SMA didn’t bother to see a neurologist in the past because we had nothing to offer them. Today, we have Spinraza, a relatively new drug that can significantly slow disease progression and, in some cases, improve strength among patients. This is a huge victory because there has never actually been a truly meaningful treatment for neuromuscular degenerative disease until now.”
Penn has one of the largest adult Spinraza programs in the nation, with the capacity to infuse the drug in patients with complicated anatomy.
“Since the drug is given by lumbar puncture and many patients have had complex orthopedic surgery or rods put in for scoliosis, infusion of this drug can be challenging,” Dr. Elman explains. “At Penn, we formed a team with specialists from neurology, interventional radiology and pharmacy to accomplish this. Four loading doses are given over a 10-week period and then every four months after that. We were one of the first adult-only centers to administer the drug.”
Where Spinraza is having the most profound affect is in the pediatric population, according to Dr. Elman.
“In children, the drug is reinventing the natural history of this disease,” she says. “Children with SMA1 used to die in childhood, but now they’re not and that means we’re in uncharted territory. At Penn, we are collecting clinical data on adults being treated with the drug, since no adults were involved in the initial clinical trials.”
Fueling Hope for the Future
Another cutting-edge therapy offered at Penn for neuromuscular disease is Exondys51, which is an exon-skipping therapy for patients with Duchenne muscular dystrophy. Approximately 13 percent of patients with Duchenne are amenable to this drug, as it is mutation-specific. It is still early days in determining the clinical benefit of this drug in adults, but so far, it is well-tolerated and many patients are eager to try it. Exondys51 is the first in class and drugs of similar mechanism that will target other mutations are currently in late-stage trials.
“Because of the new and projected availability of mutation-specific treatments, we’re aggressive to make sure that all of our patients know their mutations, so they know if they are amenable to drugs or not,” Dr. Elman says. “Additionally, gene therapy for Duchenne is an active and exciting area of research.”
Thanks to an established relationship with the Children’s Hospital of Philadelphia (CHOP), Penn often assumes care of patients with childhood-onset muscle and nerve diseases once they reach adulthood. The Penn clinicians share a joint conference with the neuromuscular specialists at CHOP and frequently confer about diagnostic and care issues, making the transition to adult care as seamless as possible. Additionally, the Penn team is lucky to have a dedicated social worker and nurse for the MDA clinic to facilitate these transitions from pediatric to adult care.
“There has been a sea of change in this entire field, and I feel very fortunate to be involved with it,” she says. “We’re starting to see treatments we only ever dreamed of.”