New, Targeted ALS Therapies Giving Researchers Reason to Hope


Dr. Colin Quinn and Dr. Lauren Elman photo

For perhaps the first time ever, there's optimism about the direction of amyotrophic lateral sclerosis (ALS) research.

"By availing ourselves of novel therapeutics and new mechanisms of medication delivery for ALS, we've seen some promising results in treating this disease," says Lauren Elman, MD, Director of the Penn Comprehensive ALS Center. "It's a foot in the door to potentially treating multiple other forms of genetic neuromuscular disease, as well as sporadic ALS. We've never seen this before in our field, and it's quite encouraging."

Ten percent of ALS cases are familial. The remaining 90 percent of cases are idiopathic -- and therein lies the trouble with developing effective therapies for ALS, explains Colin Quinn, MD, MSPT.

Dr. Quinn is Associate Director of the Penn Comprehensive ALS Center and Director of the ALS Multidisciplinary Clinic at the Corporal Michael J. Crescenz VA Medical Center.

While treatments exist for symptoms of ALS, researchers haven't been able to identify what's at the root of the disease – making it a difficult problem to solve.

"You end up downstream of where you want to be," Dr. Quinn says.

But that appears to be changing.

ALS Genetics: Targeted Therapies on the Horizon

"The explosion in the understanding of the genetics of ALS has helped us map the disease process on a cellular level," Dr. Quinn says. "That's given us new targets we didn't have before."

"Targeted," Dr. Elman says, is the keyword among many of the new clinical trials in which she and Dr. Quinn are involved.

"We're targeting the genetically mediated forms of the disease because, to be honest, those are the lowest-hanging fruit," Dr. Elman says. "They have clear targets," she continues. "The truth of the matter is, some of the mechanisms of these medications, particularly the antisense oligonucleotides and other RNA-mediated therapeutics, lend themselves to finding other targets, even in sporadic disease. These are going to be game-changers."

New ALS Research and Trials at Penn Neurology

Dr. Elman is involved in one such study, a "first-in-human trial," where an antisense oligonucleotide is being directed at the ATXN2 gene. In 2010, researchers at Penn identified the ATXN2 gene as a risk factor for ALS. "Now, 11 years later, we're among the first to dose this drug in patients with ALS in a true example of 'bench-to bedside' research. It's really incredible," says Dr. Elman. "It's an exciting time in the neuromuscular world in general, and with ALS in particular."

Dr. Quinn is involved in Phase III of the Biogen Valor clinical trial, which is investigating the effectiveness of using synthetic RNA to bind to mutant RNA in adults with familial ALS to remove it from circulation, "with the hope," Dr. Quinn says, "it will help the cells function."

He was also the principal investigator in a drug called AMX0035. A powder comprised of sodium phenylbutyrate and tauroursodeoxycholic acid, "it works on both the endoplasmic reticulum and the mitochondria to help cells deal with stress," he says.

In a Phase II clinical trial, AMX0035 was shown to slow disease progression on the ALS Functional Rating Scale by 22 percent.

For all the recent progress, multidisciplinary clinical care remains the center's top priority. The center was one of the first of its kind to offer genetic counseling to patients and their families. Patients at Penn Comprehensive ALS Center also have access to an expansive clinical team, including a neurologist, a pulmonologist, a physical therapist, an occupational therapist, a speech and language pathologist, a dietician, a genetic counselor, and a nurse practitioner, all within the course of a single appointment.

Challenges Along the Way

The rising costs of such care, even with health insurance, can make it prohibitive for some. Dr. Elman says the center is actively fundraising to defray these costs.

Similarly, Dr. Quinn says that asking ALS patients if they're military veterans is a critical step in their care.

Since veterans are twice as likely to be diagnosed with ALS as the general population, the Department of Veterans Affairs presumes that ALS was "incurred or aggravated by service in the military," according to the ALS Association. As a result, veterans with ALS and their families and survivors are eligible for "service connected" benefits.

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The Penn Physician Blog is a resource for health care professionals featuring Penn Medicine physicians and their research, innovations, programs and events. 

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