XCGD

Friday Round Up

/ Yimy Villa / 1 Comment

Here’s a look at a couple of stories that caught our eye this week:

Jasper Therapeutics has had a busy couple of weeks. Recently they announced data from their Phase 1 clinical trial treating people with Myelodysplastic syndromes (MDS). This is a group of disorders in which immature blood-forming cells in the bone marrow become abnormal and leads to low numbers of normal blood cells, especially red blood cells. We blogged about that here.

The data showed that six patients were given JSP191 – in combination with low-dose radiation five of the six had no detectable levels of disease and the sixth patient had reduced levels.

This was a big deal for us because CIRM funded the early stage research and even a clinical trial  that led to the development of JSP191.

Now Jasper has announced it is partnering with the National Institute of Allergy and Infectious Disease in a Phase 1/2 clinical trial using JSP191, as part of a treatment for chronic granulomatous disease (CGD). Congratulations to Jasper. And congratulations to us for helping them get there.

Oh, and just to toot our horn a little bit more – it is Friday after all – we have funded other approaches to CGD including one that resulted in curing Brenden Whittaker.

OK, enough about us.

To say that this last year has been a stressful one would be something of an understatement. But it’s not just people who get stressed. Stem cells do too. And, like people, when stem cells get stressed they don’t always behave in the way you would like them to. When some people get stressed they find a cocktail can help take the edge of it. Apparently that works for stem cells as well!

Now we are not talking about slipping a Manhattan or Mai Tai into a petri dish filled with stem cells. We are talking about a very different kind of cocktail.

Researchers at the National Institutes of Health have developed what they describe as a “four-part small molecule cocktail” that can help protect a specific kind of stem cell from stress. The cell is an induced pluripotent stem cell (iPSC), which has the ability to turn into any other kind of cell in the body. iPSC’s have great potential for treating a variety of different diseases and conditions, but they’re also sensitive and without the right conditions and environment they can get stressed and that in turn can damage their DNA and lead to them dying.

In a news release Dr. Ilyas Singeç, the lead researcher, says this NIH “cocktail” could help prevent that: “The small-molecule cocktail is safeguarding cells and making stem cell use more predictable and efficient. In preventing cellular stress and DNA damage that typically occur, we’re avoiding cell death and improving the quality of surviving cells. The cocktail will become a broadly used staple of the stem cell field and boost stem cell applications in both research and the clinic.”  

The team hope this could enhance the potential therapeutic uses of iPSCs in finding treatments for diseases such as diabetes, Parkinson’s and spinal cord injury.

The study is published in the journal Nature Methods.

Stem Cell/Gene Therapy combo heals patients battling rare disorder

/ Kevin McCormack / Leave a comment
Brenden Whittaker and his dog: Photo by Colin McGuire

A few years ago, Brenden Whittaker was running out of time. Brenden was born with a rare condition called x-linked chronic granulomatous disease or XCGD. It meant he lacked a critical part of his immune system that protects against bacterial or fungal infections.

Over 22 years Brenden was in and out of the hospital hundreds of times. Twice he almost died. When antibiotics failed to clear up persistent infections surgeons had to remove parts of his lungs and liver.

Brenden felt he was running out of options. Then he signed up for a clinical trial (funded by CIRM) that would use his own stem cells to correct the problem. More than four years later Brenden is doing just fine.

And he’s not the only one. A new study, published in the journal Nature Medicine, shows that six other patients in the clinical trial are now in remission and have stopped taking any other medications.

Dr. Don Kohn: Photo courtesy UCLA

Don Kohn, the lead researcher on the team from UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, says that in the past the only “cure” for people with CGD was a bone marrow transplant, but that was rarely an option for most patients. In a news release he said finding a perfect match for a transplant was difficult, and even then, patients had to take powerful anti-rejection medications to stop their body rejecting the transplant. So, they developed another approach, using genetically re-engineered stem cells from the patient themselves.

“With this gene therapy, you can use a patient’s own stem cells instead of donor cells for a transplant. This means the cells are perfectly matched to the patient and it should be a much safer transplant, without the risks of rejection.”

The team removed blood stem cells from the patients and, in the lab, corrected the genetic mutation that caused CGD. They then returned those cells to the patients which, because they are stem cells, multiplied and created a new blood supply – one free of CGD – and repaired the immune system.

Brenden was the first of five patients treated in the US. Another four were treated in Europe. All were between the ages of 2 and 27 (CGD patients often die in their 20’s because of the impact of repeated infections).

  • Two patients died because of previously incurred infections
  • Six of the seven surviving patients have discontinued previous treatments
  • Four new patients have since been treated and are currently free of infections

Dr. Kohn said the results are really encouraging: “None of the patients had complications that you might normally see from donor cells and the results were as good as you’d get from a donor transplant — or better.”

The next step is for the researchers to work with the US Food and Drug Administration to get permission to carry out a larger trial, with the eventual goal of getting approval to make it available to all patients who need it.  

Regular readers of our blog will remember that Don Kohn also pioneered a similar approach in treating, and curing, children battling another rare immune disorder, severe combined immunodeficiency or SCID. You can read about that here.

As for Brenden, he is now in college and has his sights set on medical school. In 2016 we profiled him in our Annual Report and ran a long interview with him on the blog where he talked about the joys of mowing the lawn and learning to live without a deadly disease stalking him.