Note: This story was updated April 6, 2021, to note that the study is expected to conclude late this summer, instead of 2024.
The ALS Association, Muscular Dystrophy Association (MDA), and ALS Finding a Cure have given an additional $1.1 million to support work on a cell therapy — now in a Phase 2 trial — that could slow the progression of amyotrophic lateral sclerosis (ALS).
This award supplements the $2.4 million these three nonprofits initially gave to help launch the ongoing study into regulatory T-cells, a type of white blood cell or lymphocyte, and immune responses in ALS patients. The placebo-controlled trial (NCT04055623) involves 12 people and is taking place at one site in Boston and one in Houston.
“This additional support underscores just how promising this research is,” Kuldip Dave, vice president of research at the ALS Association, said in a press release.
Both awards went to the trial’s lead investigators: Stanley Appel, MD, co-director of Houston Methodist Neurological Institute and an ALS specialist, and James Berry, MD, PhD, chief of the division of ALS and motor neuron diseases at Massachusetts General Hospital.
Regulatory T-cells, or Tregs, are negative regulators of the immune system, meaning they work to shut down excessive inflammatory responses, such as those involved in nerve cell degeneration.
Previous work by Appel and his lab found Tregs to be at unusually low levels in ALS patients and not working as effectively as they should. Tregs help to protect the body from damaging inflammation that accelerates ALS progression, and lower levels were also linked to faster disease progression.
Appel and his team found Tregs can be isolated from patients to allow their repair. Working with Coya Therapeutics, a way was also found to convert these isolated cell into “highly functional and neuroprotective” cells, which are then infused back to the patient to circulate in the blood and fight the disease more efficiently.
“Isolation, expansion, and long-term storage of T-regs is cutting edge technology,” said Merit Cudkowicz, MD, chief medical officer for ALS Finding a Cure and director of the Sean Healey Center for ALS at Mass General. “When we learned it was more expensive than researchers initially envisioned, we came together to ensure the work could continue.”
The Phase 2a trial is comparing the safety, tolerability and activity of this cell therapy, given as monthly IV infusions for six months, against a placebo infusion in 12 people; eight are being treated. Low-dose interleukin-2 (IL-2), essential for the survival and suppressive activity of these immune cells, is also given treated patients three times each week.
After this placebo-controlled part concludes, the trial’s next six months is open-label, with all enrolled invited to either continue or begin treatment with monthly Treg plus IL-2 infusions.
Its main goal is to determine changes in Treg function at six months in treated relative to placebo patients. Additional measures will look at changes in Treg numbers, overall disease progression, and respiratory health, all again after the trial’s initial six months. This fully enrolled study is due to conclude late this summer.
This study follows a Phase 1 pilot trial (NCT03241784) in three ALS patients, which found this cell therapy safe and well tolerated, and with evidence of increases in Treg numbers and their immune suppressive abilities with each infusion. Treatment was also seen to slow the rate of disease progression over the eight Treg infusions given patients in this two-year study sponsored by Appel, with four infusions given in earlier disease stages and four at later stages.
“The early results are incredibly promising, which is why it was so critical to make sure we continue testing to learn whether this therapy can be put on a path to bring it to the patient community,” said Sharon Hesterlee, PhD, executive vice president and chief research officer for the MDA.
Coya Therapeutics, which is working with Appel, also raised $10 million in financing to help advance this Treg therapy for ALS. The company also developed a way to more efficiently isolate and repair patients’ Tregs and, using its cryopreservation (or CTreg) platform, it can freeze the expanded cells for months without them losing effectiveness.
This means, Coya stated in announcing the financing, that it can generate enough Tregs for a year of treatment in a single manufacturing process, thawing frozen cells as needed for regular infusions — essentially creating an “off-the-shelf” product tailored to each patient.
Coya calls the Treg therapy created using its process ALS001.
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