I would think that stroke leadership looks at this and says: 'We need angiogenesis in the brain post stroke. What part of this can we reuse?' We have NO stroke leadership and NO stroke strategy, NOTHING WILL OCCUR!
Check out this:
vegf-A (3 posts to April 2013)
The latest here:
Gene Therapy Allowing Heart to Grow New Blood Vessels Supported by Early Data
— Researchers are eyeing catheter-based delivery for people with refractory angina
LONG BEACH, Calif. -- A gene therapy for therapeutic angiogenesis showed promise for people with angina who had already exhausted their options for medical therapy and coronary revascularization, according to the single-arm phase I/II EXACT trial.
Identified as having so-called "no option" refractory angina, 32 study participants agreed to try one dose of XC001 -- an engineered adenovirus vector that transiently increases VEGF-A expression in the myocardium -- administered via direct transepicardial delivery following a minithoracotomy. The therapy is intended to target microvascular dysfunction and ischemia.
Results of the treatment showed no serious adverse events (SAEs) or off-target effects related to XC001 -- instead, there were 20 events possibly related to the surgery, all expected and resolved, and another 37 events that were deemed related to neither the drug nor surgery, reported Kenta Nakamura, MD, of University of Washington in Seattle, at the Society for Cardiovascular Angiography & Interventions (SCAI) annual meeting.
The study's exploratory efficacy endpoints also suggested significant 12-month improvements following XC001 therapy as administered as part of open-heart surgery:
- Total exercise duration: increase from 360 seconds at baseline to 478 seconds
- Change in total myocardial perfusion deficit on positron emission tomography (PET) imaging: -10.2% from baseline
- Time to ST depression: increase of 103.1 seconds from just under 300 seconds at baseline
- Angina frequency: decrease from an average 12.2 episodes in 2 weeks to 2.7 episodes in 2 weeks
These results, simultaneously published in Circulation: Cardiovascular Interventions, provide momentum for further study of this gene therapy.
Panelist Yiannis Chatzizisis, MD, PhD, of University of Miami Miller School of Medicine, nevertheless cautioned that the treatment appears "very aggressive" for something involving the microvasculature.
Indeed, Nakamura responded that the researchers are pivoting to percutaneous delivery in an upcoming trial for XC001. "There's lots of enthusiasm to transition this to a cath-based [procedure]," he said.
"I'm excited about this ... You have to have a blinded trial and that's in the works," said SCAI session moderator Timothy Henry, MD, of The Christ Hospital Health Network.
Meanwhile, "the number of people with refractory angina is growing and includes microvascular angina," Henry said, adding that it's "becoming crystal clear" that many of the reasons why a lot of people continue to have chest pain post-angioplasty are related to the microvasculature.
XC001 is designed to transiently grow new blood vessels to restore blood flow in the heart. It contains alternative splicing of the three isoforms of VEGF-A, which sets it apart from past attempts at therapeutic angiogenesis.
"Despite favorable preclinical evidence, clinical investigations of protein, plasmid, and adenoviral-based growth factor therapy have shown limited success. One possible explanation is that most genes are expressed naturally as multiple isoforms, while gene therapies have explored only single isoforms," the investigators explained.
Other work has supported boosting myocardial blood flow or coronary flow reserve to help people with refractory angina.
Recently, the ORBITA-COSMIC group showed that an hourglass-shaped coronary sinus reducer implant eased symptoms in such patients with stable heart disease. The Neovasc Reducer acts on the cardiac venous circulation and is supposed to redistribute blood toward ischemic territories, though the exact mechanism of benefit remains unclear and the FDA has not granted approval for the device.
Investigators are now studying how the Reducer affects exercise tolerance time in the COSIRA-II trial (for which Henry is co-principal investigator).
For the present report, the EXACT group had 32 patients with advanced coronary artery disease enrolled from 2020 to 2022 across 14 sites in the U.S.
Eligible adults had Canadian Cardiovascular Society Angina Scale class II to IV angina despite optimal medical therapy and needed to have reversible myocardial ischemia and no revascularization options. They were required to have exercise-limiting angina between 90 and 540 seconds on modified Bruce protocol exercise treadmill testing and inducible ischemia on stress PET.
Nakamura said the resulting study cohort was a "highly morbid" population with a median age of 64 years and 66% men. All patients had undergone some prior revascularization: 88% prior percutaneous coronary intervention and 75% prior coronary artery bypass grafting surgery. Over 80% were on the antianginal ranolazine. Median left ventricular ejection fraction was 56%, and 78% of the group had diabetes.
XC001 was administered in 15 0.1-mL direct heart injections guided by areas of ischemia according to PET imaging.
How patients fare in the long run remains to be seen, though Nakamura's group reported that "transient expression of the gene construct would argue against any long-term risk."
Other limitations to EXACT include its uncontrolled design, the overwhelmingly white cohort (84%), and the lack of systematic assessment of arrhythmias.
![author['full_name']](https://clf1.medpagetoday.com/media/images/author/nicoleLou_188.jpg)
Disclosures
EXACT was funded by XyloCor Therapeutics.
Nakamura disclosed relationships with XyloCor and Sana Biotechnology.
Henry is on the XyloCor steering committee.
Chatzizisis reported consulting and other personal ties to Boston Scientific and Medtronic, and holding stocks and stock options in ConKardia.
Primary Source
Society for Cardiovascular Angiography & Interventions
Source Reference: opens in a new tab or windowNakamura K, et al "VEGF gene therapy improves exercise time, ischemia, and symptoms in patients with refractory angina: results of the phase II EXACT trial" SCAI 2024.
No comments:
Post a Comment