Tackling diabetes & ALS with cell therapy

Israeli company Kadimastem is developing regenerative medicine therapies based on differentiated cells derived from human embryonic stem cells to treat diseases such as Amyotrophic lateral sclerosis (ALS) and diabetes. Catherine Longworth spoke with Kadimastem’s head of diabetes research, Kfir Molakandov to find out more.

In the 1990s, when the first transplant of islets took place, it was hailed as the cure for diabetes. But years later, the potential of islet therapy is yet to be realised due to difficulties finding donors and harvesting cells.

“Only a few thousand people have benefited from this therapy as there are not enough donors,” says Kfir Molakandov.  “But even if there were enough donor islets, the standardisation of this therapy is horrible. Every donor is different, and if you offer a therapy, it should be good, reliable, consistent, and the same for everyone.”

As the head of diabetes research at Israeli cell therapy company Kadimastem, Molakandov believes they could have the next major diabetes therapy. The Tel-Aviv listed company is leading research and development of a cell therapy comprising functional pancreatic islet cells.

The product in development, IsletRx, is clinical grade pancreatic islet cells which produce and secrete insulin and glucagon in response to blood glucose levels. Using micro-encapsulation technology, integrated within IsletRx, the islet cells are protected from attack by the host immune system.

“Diabetes is a very hard disease to manage, especially with young children. You have to calculate everything from how much you eat, the amount of insulin to inject, and how much physical exercise to take – everything has to be managed! With our therapy, we aim to make it easy by simply putting the functional cells in the patient,” Molakandov tells pharmaphorum.

Founded in 2009 by Kadimastem’s chief scientist Professor Michel Revel, the therapy is based on stem cell research from Israel’s Weizmann Institute of Science, looking at the potential of restoring activity lost in tissues due to disease damage. After developing treatments for multiple sclerosis, he turned his focus to two main disease areas – diabetes and ALS.

“Any tissue in the body can be made from the stem cells as they are immature, very easy to work with cells and can proliferate as much as we want to become whatever we want,” says Molakandov.  “We see the cells like clay in our hands that we manipulate in culture and mimic development processes. We have ways to maneuver stem cells to the destination and target tissue we want. We just accelerate the process that takes place in utero over nine months and follow the same stages in a shorter time period.”

Kadimastem’s lead product for ALS, AstroRx, is a cell therapy product containing astrocytes derived from human embryonic stem cells. The astrocyte cells are injected directly into the cerebrospinal cord fluid of the patients to support the dying motor neurons in the brain and spinal cord of ALS patients and slow progression of the disease.

In March 2021, the company completed a Phase 1/2a clinical trial at Jerusalem’s Hadassah Medical Center, which validated safety and efficacy.  The study results show a high safety profile of AstroRx cells and also demonstrated that this particular approach significantly decreased the progression of the disease for three months after AstroRx administration, when measured by ALS Functional Rating Scale-Revised (ALSFRS-S). The company aims to test multiple injections of AstroRx cells in the next round of clinical trials to try to prolong the beneficial effect.

“We want to lead a diabetes revolution”

Seeking approval

For IsletRx, Kadimastem is working with global regulatory authorities to start pre-clinical studies this year. In April 2021, the company announced it had secured $6.8 million in financing to expedite its research and development programmes.

“We anticipate that in about two years our diabetes product will be in clinical trials,” says Molakandov. “In diabetes, we have managed to demonstrate that we have the capability to manufacture the islets in a good, reproducible way and our proof-of-concept studies show that our cells are capable of ameliorating glycaemia in diabetic animals. In mice, we were able to show the dose escalating needed in order to achieve normal glycaemia, so we know most of the things that we need to know about these cells.”

Kadimastem is also developing technology to purify non-relevant cells from the production procedure by selecting the right cells to put in the patient. In fact, Kadimastem is the only cell therapy company with this capability.

“It is not a process where you get everything you want – you sometimes get impurities, so we have a method and patent to take the right cells and put them in the patient.

“For years there was no good external marker, something the cell expresses on its surface, that correlates with the phenotype of mature beta cell. We did a collaboration with scientists at the Weizmann Institute, and we actually managed to identify a single marker that correlates to what is called mature function, so we are using this marker to clear the culture and only use targeted function in the cells that we want.”

Although Kadimastem is currently focusing on type 1 and type 2 diabetes, in the future, Molakandov hopes treatment could be available to pre-diabetic people to halt progression of the disease.

“Even if you are treated with insulin and you are balanced, the body still may have experienced damage. Not many companies are doing what we do, so we understand the implications and responsibility.”

The COVID-19 pandemic has also put diabetes treatment in the spotlight due to people with diabetes being more likely to have serious complications from the virus. Clinical observations have also indicated that the condition may be a consequence of the disease.

“We want to lead a diabetes revolution,” reflects Molakandov. “Personally, I think our work now is like the dream of biologists as it combines many disciplines – tissue engineering, biomaterials, development, and large-scale production. We feel really proud to understand and execute all these functions simultaneously.”

About the interviewee

Kfir Molakandov is head of diabetes research & bioproduction specialist at Kadimastem. His academic and research career have revolved around stem cell research and therapy in diabetes.