Nav: Home

New ALS therapy in clinical trials

July 16, 2018

About 20,000 people in the United States are living with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The invariably fatal disease kills the nerve cells that control walking, eating and breathing. Few people survive more than three years after diagnosis.

Now, new research led by Washington University School of Medicine in St. Louis indicates an investigational therapy for an inherited form of ALS extends survival and reverses signs of neuromuscular damage in mice and rats. The findings, published July 16 in The Journal of Clinical Investigation, have led to a phase one/two clinical trial to investigate whether the drug could benefit people with ALS whose disease is caused by mutations in a gene called SOD1.

"This drug had an impressive effect in mice and rats with just one or two doses," said Timothy Miller, MD, PhD, the David Clayson Professor of Neurology at Washington University. "We don't know yet if this works in people, but we're very hopeful. We've completed the first phase of safety testing, and now we're working on finding the right dose."

About 10 percent of ALS cases are inherited. Of those, about a fifth are caused by mutations in SOD1. Such mutations cause the SOD1 protein to be overly active, which suggests that reducing protein levels might help ALS patients with SOD1 mutations.

Patients with ALS have few options for treatment. Only two drugs have been approved by the Food and Drug Administration (FDA) for ALS, and both only modestly slow the course of the disease.

In collaboration with Ionis Pharmaceuticals, Miller and colleagues tested DNA-based compounds that block the body from making SOD1 protein.

Miller and colleagues at Ionis tested two such compounds - known as antisense oligonucleotides, or oligos for short - in mice and rats. The animals were genetically modified to carry a mutated form of the human SOD1 gene. By a few months old, such animals start having trouble walking and feeding themselves.

Mice were given an anti-SOD1 oligo or a placebo at day 50, and a second dose about six weeks later. The mice that received the active drug maintained their weight 26 days longer and lived 37 days longer than those given the placebo, an increase in life span of 22 percent.

As a comparison, the researchers also tested the treatment in rats. The rats that received an active oligo fared much better than the ones that received the placebo. They maintained their weight more than nine weeks longer and survived eight to nine weeks longer.

The oligos also reversed signs of neuromuscular damage in the animals. By nine weeks old, mice that carry the mutant SOD1 gene are already showing molecular signs of deteriorating neuromuscular function. To find out whether the drug could reverse this decline, researchers treated 9-week-old mice with an anti-SOD1 oligo or a placebo. Muscle function steadily improved over the next eight weeks in the mice that received the active drug, while it continued to decline in the placebo group. A sign of neurological damage rose in both groups, but it rose more than twice as quickly in the mice that received the placebo than the ones given the active oligo.

Miller's colleague at the School of Medicine, Robert Bucelli, MD, PhD, an associate professor of neurology, leads a phase one/two clinical trial based on Miller's research. The trial is designed to evaluate the safety of using the oligos in people. Initial safety testing did not identify any obvious hazards. Now, they are testing different doses and regimens to find the most effective way to reduce SOD1 levels without causing unacceptable side effects.

"The phase one/two trial is really still a safety trial," Miller said. "There are not enough patients in it to really be able to accurately see an effect on disease. But we're on the cusp of testing the hypothesis that people with ALS caused by mutations in SOD1 can benefit from this treatment. We predict the effect will be good, but we can't know until we test it."
-end-
More information about the trial (number NCT02623699) can be found at clinicaltrials.gov.

Washington University School of Medicine

Related Placebo Articles:

UMN trial shows hydroxychloroquine has no benefit over placebo in preventing COVID-19
Today, University of Minnesota Medical School researchers published the results from the first randomized clinical trial testing hydroxychloroquine for the post-exposure prevention of COVID-19.
The placebo effect and psychedelic drugs: tripping on nothing?
A new study from McGill suggests that, in the right context, some people may experience psychedelic-like effects from placebos alone.
Methotrexate reduces joint damage progression over placebo in erosive hand OA
According to new research findings presented at the 2019 ACR/ARP Annual Meeting, methotrexate did not demonstrate superior efficacy over placebo for pain relief and function evolution at three and 12 months in patients with erosive hand osteoarthritis, but did significantly reduce the progression of joint damage over placebo and seems to facilitate bone remodeling in these patients.
Botulinum toxin reduces chronic migraine attacks, compared to placebo
A growing body of evidence supports the effectiveness of botulinum toxin injections in reducing the frequency of chronic migraine headaches, concludes an updated review and analysis in the January issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS).
Opioids vs. placebo, nonopioid alternatives for chronic noncancer pain
An estimated 50 million adults in the United States were living with chronic noncancer pain in 2016 and many of them were prescribed opioid medications, even though a clinical benefit is uncertain.
Probiotic no better than placebo for acute gastroenteritis in children
While probiotics are often used to treat acute gastroenteritis (also known as infectious diarrhea) in children, the latest evidence shows no significant differences in outcomes, compared to a placebo.
Most common shoulder operation is no more beneficial than placebo surgery
In a landmark study published this week in the BMJ, Finnish researchers show that one of the most common surgical procedures in the Western world is probably unnecessary.
Omega-3s from fish oil supplements no better than placebo for dry eye
Omega-3 fatty acid supplements taken orally proved no better than placebo at relieving symptoms or signs of dry eye, according to the findings of a well-controlled trial funded by the National Eye Institute (NEI), part of the National Institutes of Health.
Review of Vitamin D Research identifies ethical issues in placebo use
George Washington University's Dr. Leigh Frame reviewed several studies using placebo groups in clinical trials that may pose ethical issues.
Hydroxychloroquine no more effective than placebo for relieving osteoarthritis hand pain
Hydroxychloroquine is no more effective than placebo for relieving moderate to severe hand pain and radiographic osteoarthritis.
More Placebo News and Placebo Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.