Bioheart launches trial of genetically modified muscle stem cells
for heart repair
2 April 2010
Florida based Bioheart, Inc., (BHRT.OB) has commenced work on
its REGEN trial, a Phase I clinical trial to test genetically modified
muscle stem cells in hearts of patients suffering from congestive heart
failure (CHF).
Bioheart’s MyoCell is a regenerative cell therapy that uses
myoblasts, or muscle stem cells, that are grown from a patient’s own
muscle. MyoCell has been tested successfully on patients in four
clinical trials.
The REGEN trial is designed to test the safety and effectiveness of
a composition of muscle stem cells that have been gene-modified to
induce a greater than usual release of the SDF-1 protein. The SDF-1
protein is a molecule in the human body that, after an injury, is
naturally released by most tissues to attract stem cells. The stem
cells assist with the healing process.
Unlike other tissues, the heart muscle does not release enough SDF-1
to attract the number of stem cells that would result in complete
self-healing. As a result, scar tissue forms and impairs normal
heart function.
Results from Bioheart’s preclinical animal studies have shown that
the genetically modified MyoCell is far more effective than MyoCell
alone in accomplishing repair and tissue regeneration. With SDF-1,
there is a release of additional therapeutic proteins to assist in
the tissue repair process, resulting in a more expansive and quicker
repair. Once that repair or regeneration has occurred, the patient’s
improved heart function permits the patient to return to a normal
life style.
Karl Groth, Bioheart’s Chairman and Chief Executive Officer said,
“We are extremely proud and excited to be able to commence our
REGEN clinical trial: the first and only FDA-approved clinical study
evaluating the therapeutic benefit of combined modified gene/cell
therapy for CHF.
"Bioheart's pre-clinical results using this therapy have
demonstrated that our combined gene/cell therapy should
significantly enhance the clinical improvements we have already
observed in our Phase II/III MyoCell study. As the leader in
regenerative medicine, Bioheart, through its REGEN trial, takes the
first step toward making available a solution for the treatment of
heart failure, the most rapidly growing of all cardiovascular
disorders.
According to statistics provided by the American Heart Association,
in the US, approximately $22.5 billion are the direct and indirect
annual costs of heart failure treatment. To bring effective, safe
and cost effective clinical treatments to those with congestive
heart failure is our mission.”
The treatment with MyoCell involves taking a biopsy from the
patient’s leg muscle, transporting that biopsy to Bioheart’s cell
manufacturing facility, expanding the number of cells from the
biopsy, and inducing the cells to regress to produce precursors to
muscle cells called myoblasts. These cells know that they are muscle
cells, but do not know which muscle.
Once those precursor cells, or myoblasts, are present, they are
segregated from the muscle cells and grown until they number over 1
billion cells. The myoblasts are then transported back to the
patient’s treatment centre. Some are then injected into the
patient’s heart with a needle tipped injection catheter.
The treatment used in the REGEN trial involves genetically modifying
myoblasts, utilizing Bioheart’s proprietary process. The modified
cells are injected in the same manner into the patient’s heart. The
modified myoblasts are created using an adenovirus vector or
non-viral vector. The myoblasts will release increased levels of the
SDF-1 protein, which stimulates angiogenesis and regeneration of
tissue.
A heart attack limits adequate blood flow to the heart. In response,
the body naturally increases the level of SDF-1 protein in the heart
but not enough to heal the damaged tissue. By modifying the
myoblasts to express additional SDF-1, the SDF-1 protein levels
present in the heart are multiplied exponentially.
The additional quantities of SDF-1 protein stimulate the recruitment
of the patient’s existing stem cells to the cell transplanted area.
The recruited stem cells will assist in the tissue repair and blood
vessel formation process. Preclinical animal studies showed a 54%
improvement of heart function when the myoblasts were modified to
increase SDF-1 protein prior to injection of myoblasts as compared
to 27 percent for the animals treated using myoblasts without
modification.The animals treated with a placebo showed a decline in
function of 10%.
Howard Leonhardt, Bioheart’s Chief Scientific and Technology
Officer, who led Bioheart during the period when the genetically
modified myoblasts were being developed and tested said: "Seven
years of intense preclinical development, sponsored substantially by
Bioheart, at The Cleveland Clinic with Dr Marc Penn and the
University of Florida with Dr Barry Byrne and Dr Carl Pepine led to
this landmark clinical study."
After completing the REGEN trial, the company plans to transition
this second-generation product into its FDA approved Phase II/III
MARVEL study. Bioheart plans to further study the modified myoblasts
by treating a set of patients who are participating in the study and
observing the differences in clinical and heart function among the
modified group, those who are treated with MyoCell alone, and a
placebo group.