Cellular therapy improves signs and symptoms of Duchenne muscular
dystrophy
Clinical trial results promising for people with the debilitating
disorder
Date:
March 10, 2022
Source:
University of California - Davis Health
Summary:
A recent clinical trial has shown that cellular therapy is safe
and effective in stopping the deterioration of upper limb and heart
functions in patients with late-stage Duchenne muscular dystrophy.
FULL STORY ==========================================================================
A clinical trial at UC Davis Health and six other sites showed that a
cellular therapy offers promise for patients with late-stage Duchenne
muscular dystrophy (DMD), a rare genetic disorder causing muscle loss
and physical impairments in young people.
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The therapy appears to be safe and effective in stopping the deterioration
of upper limb and heart functions. It is the first treatment to lead
to meaningful functional improvements in the most severe cases of DMD
patients.
"HOPE-2 is the first clinical trial to test systemic cell therapy in DMD,"
said Craig McDonald, the trial's national principal investigator and lead author on the study. McDonald is the professor and chair of physical
medicine and rehabilitation and professor of pediatrics at UC Davis
Health. "The trial produced statistically significant and unprecedented stabilization of both skeletal muscle deterioration affecting the arms
and heart deterioration of structure and function in non-ambulatory DMD patients." Findings from the trial were published today in The Lancet.
Cellular therapy for muscular degeneration In the Phase II clinical
trial, the researchers used Capricor Therapeutics' CAP-1002 allogeneic cardiosphere-derived cells (CDCs) obtained from human heart muscles. These cells can reduce muscle inflammation and enhance cell regeneration.
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"The primary mechanism of the CAP-1002 therapy is to help reduce the
disease's serious chronic inflammation problems, decrease fibrosis and
improve muscle regeneration, and thereby maintain or improve critical
heart and skeletal muscle function," McDonald said.
The trial examined the long-term efficacy and safety of repeated
intravenous infusions of CAP-1002 for the treatment of late-stage DMD. It enrolled 20 patients with DMD at seven U.S. centers. The participants
were at least 10 years old with moderate weakness in their arms and
hands. They were randomly assigned to receive either CAP-1002 or a
placebo every three months for one year, with a total of four infusions.
Significant improvements in arm, hand and heart functions The team
assessed upper limb function using the scale Performance of Upper Limb
(PUL) motor function for DMD, heart function using cardiac magnetic
resonance imaging (MRI), spirometry measures of respiratory function,
and circulating biomarkers.
The researchers assessed the PUL for the participants at their
first infusion and after one year. They measured the change in the mid-level/elbow PUL scores between these two readings. The study found
a significant favorable change in participants who received CAP-1002,
compared to those who got the placebo.
There was far less deterioration of upper extremity muscle function in
the cell-treated group.
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The cardiac MRI also showed that the heart structure and function seemed
to improve in participants who received CAP-1002.
"Here we show the promise of cell therapy in preventing the progression
of heart disease in a rare genetic disease, but there is good reason to
believe that such therapy may one day also be used for more common forms
of heart failure," said co-author Eduardo Marba'n, a pioneering heart researcher who first discovered that CDCs might be useful in treating
DMD. He is the Mark Siegel Family Foundation Distinguished Professor
and executive director of the Smidt Heart Institute of the Cedars-Sinai
Medical Center in Los Angeles.
Moving forward McDonald and collaborators in other centers in the United
States are launching a Phase III clinical trial, HOPE-3. The goal of
this study is to confirm the efficacy of CAP-1002 in a larger cohort
of patients.
"The FDA has signaled that a larger Phase III study would be the next step toward gaining drug approval. We need to confirm therapeutic durability
and safety of CAP-1002 beyond 12 months for the treatment of muscular degeneration in the heart and skeleton," McDonald said.
What is Duchenne muscular dystrophy DMD is a disorder that affects about
1 in 5,000 people -- mostly boys. It usually becomes apparent in early childhood, causing progressive weakness and chronic inflammation of the skeletal, heart and respiratory muscles and delays milestones such as
sitting and walking. Patients with DMD typically lose their ability to
walk in their teenage years and develop heart and lung complications as
they age.
Treatments for DMD are limited and there is no known cure. Current
therapies that target skeletal muscles are not as effective in treating
the heart muscle weakened by DMD. A therapy that stabilizes or reverses
heart deterioration, while improving upper limb function, would be
unique in its ability to address the tremendous burden of disease seen
in advanced DMD patients.
"This cell-based therapy is innovative in that it addresses critical
needs of patients with the most severe disease burden and stabilizes
both upper limb and heart function. Therapies that address the later
stages of the disease can make a tremendous impact on the quality of
life for boys and young men with DMD and lessen the burden of care for
their families," McDonald said.
Collaborations that made HOPE possible The team collaborated with
researchers and staff at the UC Davis Alpha Stem Cell Clinic, funded by
the California Institute for Regenerative Medicine (CIRM). The HOPE-2
study was the clinic's first cellular therapeutic trial.
"We worked with the Alpha Stem Cell Clinic and benefitted from the
stellar infrastructure of the UC Davis Department of Physical Medicine
and Rehabilitation's Neuromuscular Research Lab and the Clinical and Translational Science Center (CTSC). I think this is a great testimony
to the UC Davis Health leadership in stem cell therapeutic trials and
clinical translational medicine," McDonald said.
The team also used the UC Davis Imaging Research Center to obtain cardiac
MRI data on the trial participants.
The trial (NCT03406780) was sponsored by Capricor Therapeutics.
========================================================================== Story Source: Materials provided by
University_of_California_-_Davis_Health. Note: Content may be edited
for style and length.
========================================================================== Journal Reference:
1. Craig M McDonald, Eduardo Marba'n, Suzanne Hendrix, Nathaniel Hogan,
Rachel Ruckdeschel Smith, Michelle Eagle, Richard S Finkel, Cuixia
Tian, Joanne Janas, Matthew M Harmelink, Arun S Varadhachary,
Michael D Taylor, Kan N Hor, Oscar H Mayer, Erik K Henricson, Pat
Furlong, Deborah D Ascheim, Siegfried Rogy, Paula Williams, Linda
Marba'n, Russell Butterfield, Anne Connolly, Francesco Muntoni,
Nanette C. Joyce, Maya Evans, Mehrdad Abedi, Prasanth Surampudi,
Sanjay Jhawar, Jonathan G.
Dayan, Colleen Anthonisen, Erica Goude, Alina Nicorici, Omaid
Sarwary, Poonam Prasad, Jayoon Baek, Andrew Newton, Hannah Johnson,
Kyle Kusmik, Lauri Filar, Angie Edmondson, Irina Rybalsky, Wendy
Chouteau, Anthony F.
Giordano, Aixa Rodriguez, Kristan Anderson, Germaine Wezel, Melisa
Vega, Julie Duke, Jorge Collado, Matthew Civitello, Julie Wells,
Erika Pyzik, Rebecca Rehborg, Michelle Brown, Jennifer Van Eyk,
Russell G. Rogers.
Repeated intravenous cardiosphere-derived cell therapy in late-stage
Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised,
double- blind, placebo-controlled, phase 2 trial. The Lancet,
2022; 399 (10329): 1049 DOI: 10.1016/S0140-6736(22)00012-5 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220310185956.htm
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