Successful transplantation

Hope for a cure for type 1 diabetes increases

A type 1 diabetes patient with an insulin pump

(Bild: APA/Getty Images via AFP/GETTY IMAGES/SPENCER PLATT)

For years, attempts have been made to cure type 1 diabetes, in which sufferers are dependent on insulin injections as soon as the disease breaks out. Now researchers may have come a big step closer to their goal. For the first time, it has been possible to transplant insulin-producing cells from a donor's pancreas into a diabetes patient without causing a rejection reaction.

Until now, all patients who received donor islet cells had to be treated in the same way as other organ transplant patients to prevent a rejection reaction: lifelong treatment with strong drugs that considerably weaken the immune system, with possible serious long-term complications. Now Swedish and US researchers have succeeded in developing so-called hypoimmune insulin-producing cells from the pancreas of a healthy donor.

In December last year, a patient with type 1 diabetes was treated with such genetically modified cells for the first time at Uppsala University Hospital. "Per-Ola Carlsson's team, which has had experience with 60 conventional islet cell transplants (with the need for subsequent immunosuppression; note) since 2001, implanted the 'pseudo-islet cells' into the upper arm of the unidentified patient. The transplant has so far survived for four weeks, although the patient did not receive any immunosuppressive drugs," according to a press release from the clinic. 

Using "gene scissors" to eliminate foreign tissue characteristics
Behind the medical success is a technology based on the CRISPR-Cas9 "gene scissors". In the current case, tissue characteristics were eliminated that make the cells appear "foreign" to the recipient's immune system and trigger an immediate and destructive rejection reaction. This was done in several steps. The CRISPR-Cas9 gene scissors were used to remove two immunologically active genes (B2M and CIITA) from the genetic material of the donor cells. An additional gene (CD47) was then inserted using a gene guide, as reported by the German medical journal Ärztezeitung. 

In an animal model, the transplantation of such islet cells even worked across species boundaries in two macaque monkeys (Rhesus/Java) and cured artificially induced type 1 diabetes for six months, the Sana scientists reported last year in the journal "Cell Stem Cell". 

How type 1 diabetes develops
It is not yet known to what extent insulin production has been restarted by the genetically modified islet cells in the treated patient. Details are to be published in a specialist publication. The aim would be for type 1 diabetics to no longer have to inject insulin. A cure for type 1 diabetes, in which an autoimmune reaction leads to the destruction of the insulin-producing cells in the pancreas, would be an enormous advance in medicine. The disease usually breaks out in childhood and adolescence, putting those affected at particular risk of long-term complications such as early atherosclerosis, kidney and retinal damage in later life. As soon as they are diagnosed, they are dependent on regular insulin injections and constant monitoring of blood glucose levels.