Month: August 2024

JDRF Canada Clinician Investigator Fellowship 2024 Recipient

The JDRF Canada Clinician Investigator Fellowship is open to medical residents that are pursuing an additional research degree (Master, PhD, or postdoctoral training) in the field of type 1 diabetes research. Residents must be part of their university’s Clinician Investigator Program (CIP) which is guided by The Royal College of Physicians and Surgeons of Canada. The major goal of the CIP is to assist in the career development of clinician investigators in Canada. At the end of the research component of the program, the resident will be expected to have acquired the knowledge, skills, and attitudes fundamental to embarking on a career in health research.

Dr. Ahsen Chaudhry is the first recipient of the JDRF Canada Clinician Investigator Fellowship. He completed his medical degree at the University of British Columbia in 2019 and became a Fellow of the Royal College of Physicians of Canada as a certified physician in 2023.  Ahsen will now be pursuing a research-based master’s degree via the UBC Clinician Investigator Program.

Dr. Timothy Kieffer, who will supervise Dr. Chaudhry’s research, emphasized the importance of this fellowship: “Ahsen has demonstrated a passion for the role of a clinician-scientist and has a strong aptitude for integrating research into his clinical practice. This program will provide Ahsen with the skills necessary to facilitate the further development of his academic endocrinology career, with a special focus on cell therapy for diabetes. It is important that we build additional capacity and encourage promising fellows like Ahsen to pursue this area of research, to maintain our world leadership in [the type 1 diabetes cell therapy] field.”

JDRF had the pleasure of connecting with Dr. Chaudhry to congratulate him on his new fellowship and discuss his research.  

Tell us a bit about your background:

“I grew up in Prince George, BC, where I completed my undergraduate degree in Biochemistry and Molecular Biology at the University of Northern British Columbia. I moved to Vancouver to attend medical school at UBC, where I then completed my residency in Internal Medicine and sub-specialty training in Endocrinology.”

What drew you to medicine in general and to diabetes? 

“Medicine is a gratifying field that combines the rigour of science, the art of patient care, and the spirit of compassion. The ability to make a tangible difference in someone’s life by combining these aspects is what motivated me to pursue medicine. My interest in diabetes developed early from exposures in my undergraduate studies and medical school, where I was fortunate to join research on diabetes and pancreatic beta-cell physiology. I was humbled by the fascinating cellular processes and web of interacting systems that underpin this disorder, and how much we still have to learn. As I progressed further through my medical training, I witnessed the heavy burden and human cost that diabetes has. It is a chronic condition with a number of serious complications and impacts on quality of life, and it is sincerely a privilege to work with patients on a long-term basis to help them manage their diabetes and maintain their health.”

Why do you want to do research in this area?

“Although the field has come very far since the momentous discovery of insulin, there is still much work to be done to improve diabetes care and help relieve the many challenges faced by people living with diabetes. Thankfully, we are at the cusp of an exciting revolution, particularly for Type 1 Diabetes (T1D), with the advent of stem-cell therapy that has the potential to make beta-cell and islet replacements a functional cure for T1D. By pursuing both clinical and basic science training in diabetes and islet/stem cell transplant, I hope to help contribute to this exciting area by helping the discoveries made at the bench progress through clinical trials and then eventually to clinical practice.”

What will you investigate during your Clinician Investigator Fellowship?

“My main project will focus on investigating the use of miRNA-based biomarkers for characterizing graft cell death in patients who have undergone stem cell derived pancreatic progenitor implants as well as cadaveric islet cell transplants, under the mentorship of Dr. Timothy Kieffer. The aim is to develop a non-invasive method for tracking the viability and natural history of these cells, which could help impact future clinical trials and patient management by giving insight into where protocol changes and optimizations need to be made. I will also be assisting with and recruiting for clinical trials of patients receiving novel stem cell-based beta-cell replacement therapies. Additionally, I will be receiving clinical training in islet transplantation and transplant endocrinology during my fellowship.”

How will the JDRF Fellowship support your research?

“The fellowship provides crucial funding that will support me in my clinical and research training, assisting me to become an independent clinician-scientist focused on translational research in diabetes and transplantation. Moreover, by enabling the opportunity to work at the JDRF Center of Excellence in UBC, I am privileged to be able to collaborate and network with leading experts, as Vancouver is home to amazing scientists who are world-leaders in several aspects of T1D research. This is so meaningful in helping my research benefit from and contribute to the broader diabetes research community. We are also rapidly expanding clinical activity and infrastructure in islet transplantation and clinical trials in Vancouver that are informed heavily by a lot of research that has been done here. JDRF’s support is instrumental to cementing this growing collaboration between researchers and clinicians in Vancouver that can help it become a key center for islet transplantation, cell therapy, and innovation in T1D. Ultimately, we hope this will translate to the most important goal of all, improving the lives and outcomes of our patients.”

JDRF Canada thanks Dr. Chaudhry for his time and congratulates him on the fellowship award. We wish him the best of luck with his research work, and we will share research updates when they become available. 

Celebrating a 55th ‘Diaversary’ with an ambitious fundraiser 

Miguel Alvarez, who has been living with type 1 diabetes for over 55 years, aims to complete two bike rides of over 100 miles each.  

To mark his 55th ‘Diaversary’ – the date when someone was diagnosed with type 1 diabetes (T1D), Vancouver, BC resident Miguel Alvarez will be attempting two 100-mile bike rides: the first in Coeur d’Alene, Idaho in September, and the second in Death Valley, California the following month in October.  Training for these rides requires dedication, discipline and perseverance, much like daily life with T1D.  Miguel will need to put in many hours on the bike but believes if he can help further progress to find a cure for T1D, it will be worth the effort. It’s why he rides. 

JDRF was recently able to talk with Miguel, learn more about his five plus decades living with T1D, what drives him to set these ambitious bike ride challenges, and what he hopes to achieve with his fundraiser. 

*** 

I’m originally from Ontario. I’ve worn a few hats in my life. I used to be a professional musician as a drummer and played in the Toronto area in a number of bands and pretty much every music venue throughout Southwestern Ontario. I’ve also worked as a motorsports photographer, and I presently work in technology, after moving to Vancouver.  

I was three years old, in 1969, when I was diagnosed with type 1 diabetes. This is now my 55th year living with T1D. One of my earliest childhood memories is being in the hospital, after being diagnosed. It was a traumatic experience. Having visitors was a difficult thing back then, family visits were limited and nobody under the age of 12 was allowed to visit, so my sister couldn’t come to see me. I remember being continually poked with needles, having my blood drawn, things like that. Suffice it to say, these are not nice memories, especially being so formative and some of my first.  

And I remember growing up trying to be ‘normal’, but T1D was always present, getting in the way. Much as I tried not to let it affect me. Back then, there was very little in terms of management. We only had one type of insulin. Diet was critical because that was the way to control it. But it was very restrictive. I remember going trick or treating at Halloween and not being allowed to eat any of the candy (it went to my sister) or going to friends’ birthday parties and not being allowed to have any birthday cake. These might not seem like big things, but they were just something else that singled me out as different. 

One thing I do feel very fortunate about it is that I was always able as a child to know when I was having a low (hypoglycemia), and I really believe this is one of the reasons I was able to survive 55 years with this condition. I always knew and could communicate to my parents to let them know I wasn’t feeling well, or that I was feeling ‘off’. That I knew I was going low. I’m very lucky that I have always had symptoms of low blood sugar. Many people cannot and that is serious. With the lack of available tools to manage T1D, this was a huge advantage, if you can say that about having this chronic condition. 

Over time, it is human nature, you learn to live with it (having T1D). I always try to express to people that I’ve basically lived through almost all the advancements of diabetes management, to date. There was no home glucose testing, no different types or better types of insulins, devices like insulin pumps, advanced glucose monitors like CGMs. All the progress in T1D management has directly impacted my life for the better.  So, in some way, I feel that I’m a reflection of the best that has come forward in diabetes management, and I can say with certainty that they have not only improved my life but prolonged my life as well.  

I’ve always been very open talking to people about diabetes, what it’s like and educating people along the way. The reality is, when I’m asking for money for my fundraiser – I explain that through the research that’s being done, I am a beneficiary of it. It’s not abstract, it’s very concrete. I am one of the few that can say that your donations over the years have benefited me personally.  

I’ve found that for people without any personal knowledge of T1D, there is often a misconception that you take insulin and you’re fine. They don’t understand the daily, even hourly management it takes. It’s far more than many people would be able to manage. But it’s something we have to do, every single day. This isn’t about sympathy, it’s just the reflection and reality of living with a chronic disease that affects your everyday life.  

And the mental burden, people don’t always have an appreciation for it. That’s the other aspect. It doesn’t affect just me; it affects everyone around me. My family, my wife, when I’m on a bike ride, I need to be extra vigilant, far more than the average person. It’s not just dealing with one thing; this condition is multi-faceted. And those facets change every day. As much as you try and be consistent, and apply what you think works, there is no explanation when things change or don’t work. No two days are the same. You are always behind the ball. Some days are good, some days are bad. But it’s so hard to juggle all the variables, because you don’t really have control over that. And then there is the tendency to beat yourself up when your control (blood glucose levels) isn’t as good as you want it to be. Then you feel bad. We can be very hard on ourselves too. 

Every single day, I think about the potential T1D-related complications, from my eyes to my kidneys to my feet, I’m always thinking about it. And that weighs on me. It’s one thing to live with a chronic condition. But knowing that there are long-term complications that can happen, it’s hard to live with. I’m very concerned about my eyesight. I’m an artistic person. I use my eyes for my work and my creativity. But there is no choice. We do what we must do. And it’s another reason why I am so driven to fundraise to help support critical T1D research. 

I’ve been doing these bike rides since 2017, in fact, I hadn’t really connected with JDRF until 2016. And when I did, it was the first time in my life that I met people who understood and knew what I was dealing with. It was a huge deal for me. I had never known anyone else with T1D. I grew up alone with this. I didn’t want to just go and ride my bike for the sake of riding, I wanted to do something with it, use it as a tool. I could make a difference, do the thing I love to do, being healthy and riding my bike, and I could raise money for such an important cause and connect with a community, everyone single-mindedly working towards the same goal. I’ve met so many other people now who know what this (life with T1D) is about. I started making friends in the T1D community in the US, and now I go pretty much every year. Working towards these events and raising money – my donors, I keep going back to them, and they keep supporting me. They appreciate that I am doing something so tangible towards T1D research. I do a lot of training to be able to ride 100 miles, and I’m doing it twice in 2024. Which is physically exhausting, but it’s so empowering and so uplifting. It’s quite amazing. 

To anyone thinking of becoming involved with JDRF, please know that it makes a difference. And when I say that I use my personal experience knowing what that difference is, and how profound. Everyone’s time and efforts, whether volunteering or fundraising, does have an enormous impact. This is an investment, the results might not be immediate, but we are investing in future generations and in humanity. 

So, towards that end, I’m also in the early stages of participating in a clinical trial, potentially early next year (2025). It seems like I’m a strong candidate. This particular study will implant beta cells (the cells responsible for producing insulin). Essentially, it’s a package of beta cells that are implanted through a surgical procedure. If it works, I wouldn’t need to inject insulin. It’s still early days, but they are interested in me participating. It won’t be easy as I have to be prepared for multiple surgeries. But I know I will get excellent medical attention through the process. I see it as putting my money where my mouth is. I am going to participate directly in finding a cure.  

What would a cure mean to me?  On the one hand, living with this all my life, it’s become part of my identity. So, if I am no longer diabetic, who am I? It would be a huge mental shift. But not having to manage T1D anymore, would be a whole new life. I would be confident that the future would mean living a less complicated life. My father always used to tell me that they would find a cure in my lifetime, and I want to prove him right. I want to see that happen for us both. 

I would love to go for a bike ride and not worry about going low (blood glucose levels). Not needing to take extra food with me every time. Not having to check my Dexcom (CGM device) constantly. Just going for a ride for the pure pleasure of riding. I want to experience that. That’s something I want to try. 

To learn more about Miguel’s fundraiser, please visit: https://jdrf.akaraisin.com/ui/YourWay2024/p/miguel55 

To build your own ‘Diaversary’ fundraising campaign, please visit:  https://jdrf.akaraisin.com/ui/YourWay2024/mark-your-diaversary

Exciting updates from Vertex stem cell-based therapy clinical trials

A large area of cure-based T1D research is investigating stem cell-based therapy. The goal of this approach is to use stem cells as a renewable source of insulin-producing cells which, when transplanted, would replace beta cells that are destroyed in a person with T1D, thereby allowing them to produce insulin again. This would lessen or eliminate the amount of external insulin required by someone living with T1D (either by injection, pen, or pump) for months or even decades.

Vertex currently has two active clinical trials for type 1 diabetes cell therapy: VX-880 (FORWARD) and VX-264 (UPWARD). These are phase 1/2 clinical trials meaning that they assess both safety and efficacy of the stem cell-based product.  The trials happen in 3 parts:

  1. Part A: small number of participants receive a partial “dose” of the transplanted cells. These participants are staggered, meaning that there was a delay of a few months before each additional participant started the trial to ensure that the participant before them was tolerating the dose well.
  2. Part B: following review of Part A results, a larger number of participants receive the full, target “dose” of the transplanted cells. The participants are still staggered.
  3. Part C: following review of Part B results, more participants receive the full, target “dose” of the transplanted cells. The participants are no longer staggered and can be dosed simultaneously.

Vertex VX-880: FORWARD Trial

November 2024:

On November 4th, 2024, Vertex Pharmaceuticals made an important announcement that their Phase 1/2 clinical trial for their stem cell therapy VX-880 is converting into a Phase 1/2/3 pivotal trial following successful Phase 2 review by regulatory bodies. A pivotal trial gathers the data required for a regulatory submission (to Health Canada or other regulators such as the FDA) to bring the therapy to the market. This will build upon the ongoing international trial (including 4 Canadian sites) and increase the number of participants from 37 to 50.

February 2021: 

Vertex announced the launch of a Phase 1/2 clinical trial for VX-880, a stem cell-derived therapy people with T1D. VX-880 is delivered via infusion into the hepatic portal vein (liver) and requires the use of chronic immunosuppressive therapy to protect the cells from rejection or immune attack. VX-880 is being tested in people with T1D who have severe hypoglycemia and impaired hypoglycemia unawareness.

October 2021 (Part A):

Vertex announced that the first trial participant to receive VX-880 now needs 91% less insulin 90 days after receiving an infusion of these stem cells – and at just half the target dose. The success seen with just half the target dose is exciting as it suggests a lower level of this therapy may still yield positive results.

June 2023 (Part B):

Six patients have received full doses of VX-880 at staggered times over the past year and a half. Prior to treatment, all patients had undetectable fasting C-peptide (i.e., no self-secreted insulin, or insulin produced by the body), a history of recurrent severe hypoglycemic events in the year prior to treatment and required an average of 34.0 units of insulin per day.

Following treatment, all six patients are self-secreting insulin, improved HbA1c levels, improved time-in-range on continuous glucose monitoring, and reduction or elimination of exogenous insulin use (i.e., externally administered insulin either by pen, pump or multiple daily injection). Patients with greater than 90 days of follow-up also had elimination of severe hypoglycemic events. Two of the six patients are at least 12 months post-treatment and are currently insulin independent with “normal” HbA1c levels (≤6.0%) and time-in-range levels over 95%.

VX-880 has been well tolerated with only mild-moderate adverse events such as: dehydration, diarrhea, hypomagnesemia and rash.

Based on the result of these safety and efficacy data in Part B, the independent data review committee has recommended moving to Part C of the trial, which allows for concurrent dosing of patients at the full target dose of VX-880. Approximately 10 participants will be enrolled in this stage of the trial.

June 2024 (Part B/C results):

Vertex reports VX-880 preliminary results: Of the 12 patients who have been dosed, nearly all (11 of 12) have had a reduction or elimination of exogenous insulin use (via pump or injection). All patients have achieved an HbA1C below 7.0% and time-in-range above 70% on continuous glucose monitoring with the reduced or eliminated insulin administration. There have been no serious adverse events reported. The trial is expanding recruitment for 37 participants to progress towards pivotal development.Recruitment is currently ongoing in Edmonton, Toronto, Montreal and Vancouver.

Vertex VX-264: UPWARD trial

This treatment will use the same cell therapy as VX-880, but encapsulate the cells within a device designed to shield the cells from the body’s immune system. Therefore, immunosuppression is not expected to be required.

August 2024 (Part A):

Vertex reported that they have completed Part A of the trial. Results from these participants are anticipated early 2025.  They have received approval to begin Part B of the trial and are currently enrolling and dosing participants. Recruitment is currently ongoing in Edmonton, Toronto, and Vancouver.

Vertex partners with Lonza (Switzerland) to build a dedicated manufacturing facility for T1D cell therapies

In June 2023, Vertex and Lonza announced that they will partner in the process development and scale-up for the manufacturing of the VX-880 and VX-264 product portfolio and co-invest to build a dedicated new facility in Portsmouth, New Hampshire. Operated by Lonza, the facility will span more than 130,000 square feet and is anticipated to create up to 300 new jobs at peak capacity. Construction is scheduled to begin later this year. For more information, please see the full press release here.

How is success of these clinical trials measured?

The primary goal of a phase 1/2 trial is to assess safety as well as efficacy of the product. Safety and tolerability are assessed by the number of adverse events. Efficacy is assessed by measuring C-peptide levels (a marker that directly indicates insulin production by beta cells), HbA1c (a measure of average blood glucose over 2-3 months), and reduction in severe hypoglycemic events.

 HbA1c will also be measured

JDRF’s Role

JDRF’s involvement can first be traced back to 2000, when Douglas Melton, Ph.D. was given a JDRF grant to make insulin-producing beta cells from stem cells—which he did in 2014.

Since then:

  • In 2015 Dr. Melton founded Semma Therapeutics to develop these stem cells into curative therapies for T1D.
  • In 2017, the JDRF T1D Fund made a significant investment in Semma.
  • In 2019, Vertex acquired Semma for almost $1 billion USD.
  • In March 2021, VX-880 received fast-track designation from the US Food and Drug Administration (FDA).

JDRF globally has prioritized stem cell therapy as a potential cure-based therapy and will continue to investigate and fund the most promising research.

What does this mean for Canadians with T1D?

For cell therapy to be broadly accessible to people with T1D, the cell product needs to both work and function without or with minimal immunosuppressive therapies. The VX-880 has expanded recruitment to 37 participants to progress toward pivotal development, which is a step towards potential approval for market. VX-264 is still currently in early stages of trial. Lastly, Vertex has another product in development (not yet in clinical trials) in partnership with CRISPR Therapeutics which will include gene editing.

JDRF Canada will continue to monitor results and provide updates as they are made public.