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Pharmaceuticals

A Cure for Type 1 Diabetes? For One Man, It Seems to Have Worked.

Source: The New York Times

A new treatment using stem cells that produce insulin has surprised experts and given them hope for the 1.5 million Americans living with the disease.

Brian Shelton’s life was ruled by Type 1 diabetes.

When his blood sugar plummeted, he would lose consciousness without warning. He crashed his motorcycle into a wall. He passed out in a customer’s yard while delivering mail. Following that episode, his supervisor told him to retire, after a quarter century in the Postal Service. He was 57.

His ex-wife, Cindy Shelton, took him into her home in Elyria, Ohio. “I was afraid to leave him alone all day,” she said.

Early this year, she spotted a call for people with Type 1 diabetes to participate in a clinical trial by Vertex Pharmaceuticals. The company was testing a treatment developed over decades by a scientist who vowed to find a cure after his baby son and then his teenage daughter got the devastating disease.

Mr. Shelton was the first patient. On June 29, he got an infusion of cells, grown from stem cells but just like the insulin-producing pancreas cells his body lacked.

Now his body automatically controls its insulin and blood sugar levels.

Mr. Shelton, now 64, may be the first person cured of the disease with a new treatment that has experts daring to hope that help may be coming for many of the 1.5 million Americans suffering from Type 1 diabetes.

“It’s a whole new life,” Mr. Shelton said. “It’s like a miracle.”

Diabetes experts were astonished but urged caution. The study is continuing and will take five years, involving 17 people with severe cases of Type 1 diabetes. It is not intended as a treatment for the more common Type 2 diabetes.

“We’ve been looking for something like this to happen literally for decades,” said Dr. Irl Hirsch, a diabetes expert at the University of Washington who was not involved in the research. He wants to see the result, not yet published in a peer-reviewed journal, replicated in many more people. He also wants to know if there will be unanticipated adverse effects and if the cells will last for a lifetime or if the treatment would have to be repeated.

But, he said, “bottom line, it is an amazing result.”

Dr. Peter Butler, a diabetes expert at U.C.L.A. who also was not involved with the research, agreed while offering the same caveats.

“It is a remarkable result,” Dr. Butler said. “To be able to reverse diabetes by giving them back the cells they are missing is comparable to the miracle when insulin was first available 100 years ago.”

And it all started with the 30-year quest of a Harvard University biologist, Doug Melton.

Dr. Melton had never thought much about diabetes until 1991 when his 6-month-old baby boy, Sam, began shaking, vomiting and panting.

“He was so sick, and the pediatrician didn’t know what it was,” Dr. Melton said. He and his wife Gail O’Keefe rushed their baby to Boston Children’s Hospital. Sam’s urine was brimming with sugar — a sign of diabetes.

The disease, which occurs when the body’s immune system destroys the insulin-secreting islet cells of the pancreas, often starts around age 13 or 14. Unlike the more common and milder Type 2 diabetes, Type 1 is quickly lethal unless patients get injections of insulin. No one spontaneously gets better.

“It’s a terrible, terrible disease,” said Dr. Butler at U.C.L.A.

Patients are at risk of going blind — diabetes is the leading cause of blindness in this country. It is also the leading cause of kidney failure. People with Type 1 diabetes are at risk of having their legs amputated and of death in the night because their blood sugar plummets during sleep. Diabetes greatly increases their likelihood of having a heart attack or stroke. It weakens the immune system — one of Dr. Butler’s fully vaccinated diabetes patients recently died from Covid-19.

Added to the burden of the disease is the high cost of insulin, whose price has risen each year.

The only cure that has ever worked is a pancreas transplant or a transplant of the insulin-producing cell clusters of the pancreas, known as islet cells, from an organ donor’s pancreas. But a shortage of organs makes such an approach an impossibility for the vast majority with the disease.

“Even if we were in utopia, we would never have enough pancreases,” said Dr. Ali Naji, a transplant surgeon at the University of Pennsylvania who pioneered islet cell transplants and is now a principal investigator for the trial that treated Mr. Shelton.

For Dr. Melton and Ms. O’Keefe, caring for an infant with the disease was terrifying. Ms. O’Keefe had to prick Sam’s fingers and feet to check his blood sugar four times a day. Then she had to inject him with insulin. For a baby that young, insulin was not even sold in the proper dose. His parents had to dilute it.

“Gail said to me, ‘If I’m doing this you have to figure out this damn disease,’” Dr. Melton recalled. In time, their daughter Emma, four years older than Sam, would develop the disease too, when she was 14.

Dr. Melton had been studying frog development but abandoned that work, determined to find a cure for diabetes. He turned to embryonic stem cells, which have the potential to become any cell in the body. His goal was to turn them into islet cells to treat patients.

One problem was the source of the cells — they came from unused fertilized eggs from a fertility clinic. But in August 2001, President George W. Bush barred using federal money for research with human embryos. Dr. Melton had to sever his stem cell lab from everything else at Harvard. He got private funding from the Howard Hughes Medical Institute, Harvard and philanthropists to set up a completely separate lab with an accountant who kept all its expenses separate, down to the light bulbs.

Over the 20 years it took the lab of 15 or so people to successfully convert stem cells into islet cells, Dr. Melton estimates the project cost about $50 million.

The challenge was to figure out what sequence of chemical messages would turn stem cells into insulin-secreting islet cells. The work involved unraveling normal pancreatic development, figuring out how islets are made in the pancreas and conducting endless experiments to steer embryonic stem cells to becoming islets. It was slow going.

After years when nothing worked, a small team of researchers, including Felicia Pagliuca, a postdoctoral researcher, was in the lab one night in 2014, doing one more experiment.

“We weren’t very optimistic,” she said. They had put a dye into the liquid where the stem cells were growing. The liquid would turn blue if the cells made insulin.

Her husband had already called asking when was she coming home. Then she saw a faint blue tinge that got darker and darker. She and the others were ecstatic. For the first time, they had made functioning pancreatic islet cells from embryonic stem cells.

The lab celebrated with a little party and a cake. Then they had bright blue wool caps made for themselves with five circles colored red, yellow, green, blue and purple to represent the stages the stem cells had to pass through to become functioning islet cells. They’d always hoped for purple but had until then kept getting stuck at green.

The next step for Dr. Melton, knowing he’d need more resources to make a drug that could get to market, was starting a company.

His company Semma was founded in 2014, a mix of Sam and Emma’s names.

One challenge was to figure out how to grow islet cells in large quantities with a method others could repeat. That took five years.

The company, led by Bastiano Sanna, a cell and gene therapy expert, tested its cells in mice and rats, showing they functioned well and cured diabetes in rodents.

At that point, the next step — a clinical trial in patients — needed a large, well financed and experienced company with hundreds of employees. Everything had to be done to the exacting standards of the Food and Drug Administration — thousands of pages of documents prepared, and clinical trials planned.

Chance intervened. In April 2019, at a meeting at Massachusetts General Hospital, Dr. Melton ran into a former colleague, Dr. David Altshuler, who had been a professor of genetics and medicine at Harvard and the deputy director of the Broad Institute. Over lunch, Dr. Altshuler, who had become the chief scientific officer at Vertex Pharmaceuticals, asked Dr. Melton what was new.

Dr. Melton took out a small glass vial with a bright purple pellet at the bottom.

“These are islet cells that we made at Semma,” he told Dr. Altshuler.

Vertex focuses on human diseases whose biology is understood. “I think there might be an opportunity,” Dr. Altshuler told him.

Meetings followed and eight weeks later, Vertex acquired Semma for $950 million. With the acquisition, Dr. Sanna became an executive vice president at Vertex.

The company will not announce a price for its diabetes treatment until it is approved. But it is likely to be expensive. Like other companies, Vertex has enraged patients with high prices for drugs that are difficult and expensive to make.

Vertex’s challenge was to make sure the production process worked every time and that the cells would be safe if injected into patients. Employees working under scrupulously sterile conditions monitored vessels of solutions containing nutrients and biochemical signals where stem cells were turning into islet cells.

Less than two years after Semma was acquired, the F.D.A. allowed Vertex to begin a clinical trial with Mr. Shelton as its initial patient.

Like patients who get pancreas transplants, Mr. Shelton has to take drugs that suppress his immune system. He says they cause him no side effects, and he finds them far less onerous or risky than constantly monitoring his blood sugar and taking insulin. He will have to continue taking them to prevent his body from rejecting the infused cells.

But Dr. John Buse, a diabetes expert at the University of North Carolina who has no connection to Vertex, said the immunosuppression gives him pause. “We need to carefully evaluate the trade-off between the burdens of diabetes and the potential complications from immunosuppressive medications.”

Mr. Shelton’s treatment, known as an early phase safety trial, called for careful follow-up and required starting with half the dose that would be used later in the trial, noted Dr. James Markmann, Mr. Shelton’s surgeon at Mass General who is working with Vertex on the trial. No one expected the cells to function so well, he said.

“The result is so striking,” Dr. Markmann said, “It’s a real leap forward for the field.”

Last month, Vertex was ready to reveal the results to Dr. Melton. He did not expect much.

“I was prepared to give them a pep talk,” he said.

Dr. Melton, normally a calm man, was jittery during what felt like a moment of truth. He had spent decades and all of his passion on this project. By the end of the Vertex team’s presentation, a huge smile broke out on his face; the data were for real.

He left Vertex and went home for dinner with Sam, Emma and Ms. O’Keefe. When they sat down to eat, Dr. Melton told them the results.

“Let’s just say there were a lot of tears and hugs.”

For Mr. Shelton the moment of truth came a few days after the procedure, when he left the hospital. He measured his blood sugar. It was perfect. He and Ms. Shelton had a meal. His blood sugar remained in the normal range.

Mr. Shelton wept when he saw the measurement.

“The only thing I can say is ‘thank you.’”

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Lifestyle

Keeping pets protected during heatwaves this summer

We’ve been lucky to have been hit with some great weather this summer, however, some days have been exceptionally hot and causing us discomfort to the point where we don’t want to leave the house! Our pets can also struggle in this heat and if not looked after correctly, can lead to life threatening issues for them. 

Dr. Sarah Machell, Medical Director for Vetster, has shared her top five top tips to ensure that our pets can enjoy the summer days as much as we can.

Vetster, is a digital platform that connects licensed vets with pet owners virtually, with 24/7 online appointments, launches in the UK this summer.

1.  Provide adequate rest, shade, and ventilation

Coping with high temperatures and humidity is tough enough on its own, but it’s even more difficult for pets who are exercising in direct sunlight and don’t have adequate ventilation. Limit outdoor activities to early mornings and late evenings when it’s cooler. When walking your pet, choose shady routes off the pavement.  Ensure outdoor pets have shady, ventilated places to escape the heat.  Keep in mind that pets also rely on evaporation for cooling, regardless of if they sweat like horses or pant like dogs, and high humidity decreases the effect of evaporation. This means your pet needs you to keep an eye on the heat index for them as well as for you.  Be sure your pets have easy access to a steady supply of clean water. Pets are naturally wired to stay hydrated as long as they are healthy and avoid heavy exercise in the heat, so there’s no need to try to encourage your pet to drink more.  Just make sure the water supply is in easy reach and doesn’t run dry. 

 2. Be wary of paws on the hot pavement! 

When the weather gets extremely hot, so does the pavement—asphalt, in particular. If you’re taking your dog out for a walk, try to remember that they don’t have shoes to protect against the heat. Even though paw pads are extremely tough, hot surfaces can burn them. Consider using padded booties for their paws to create a barrier between paw pads and the hot concrete.  Better yet, try to steer clear of the streets and walk on the cool grass instead. If there’s an opportunity to wade through some clean water or catch the spray from a sprinkler, that’s even better. Remember that pavement retains heat and you still need to be aware of the risks when you go for walks in the evening.

3. Look out for signs of heatstroke 

Heatstroke is a very serious condition and one to look out for in your pets. As a pet parent, it’s important to be aware of your pet’s fitness level and avoid overexertion when the weather’s too hot or humid. Less athletic dogs, dogs with underlying illnesses, and brachycephalic breeds are at higher risk for developing heatstroke, so keep an extra close eye on them. Heatstroke is life-threatening, but it can be avoided if you take action to cool your pet when they show early signs of heat stress. If your dog doesn’t want to keep walking, lies down in the shade, or digs up cool dirt to lie in, those are clues they’re getting too hot.  Excessive panting that doesn’t improve after a short rest is another indicator. Get out of the heat and offer water to keep the threat of heatstroke from escalating.  Splash down hot ears, paws, and bellies with water to achieve more rapid cooling.

4 Never leave your pet unattended in a hot vehicle 

Heatstroke can happen in the blink of an eye—it cannot be stressed enough that you should never, ever leave your pet unattended in a vehicle. This is true even if you leave the windows down for fresh air or if you think you’ll only be gone for a few minutes. Studies show that even if the outdoor temperature is 72℉ (22°C), a car can rise up to 117℉ (47°C) in only an hour. Imagine how quickly a car can become dangerously hot when outdoor temperatures are a balmy 86℉ (30°C). Even if you’re leaving your car unattended for a minute or think that leaving a window open will help – the life-or-death gamble you’re taking isn’t worth it.

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Pharmaceuticals

Why dosage matters in menopause treatment

By Rizvan Faruk Batha MPharm, PGDip GPP, IPresc, MRPharmS, Superintendent Pharmacist of Specialist Pharmacy.

Bioidentical Hormone Restoration Therapy (BHRT) is an alternative option to traditional synthetic HRT, using bioidentical hormones to treat hormonal conditions in both men and women. BHRT is compounded medicine and put simply, means that the individualised ingredients are mixed together under the direction of a qualified prescriber’s prescription to meet the tailored needs of a patient.

For women going through menopause, compounding treatments are often prescribed later down the line, when a woman has been unable to settle on the appropriate dose of HRT with a General Practitioner, often experiencing severe side effects from either too much or too little HRT. In short, compounded menopause medication offers another route for those patients where the licensed preparation is not appropriate or hasn’t worked.

Patient-led care plays an important role in compounded menopause medicine because the patient is involved throughout the process; during the consultation with the prescribing practitioner, and with the pharmacist developing the customised dosage.

One of the biggest challenges faced by compounding pharmacies is the drugs being classified as unlicensed. For drugs to be licensed, it involves research and clinical trials to assess the efficacy, quality, and safety of the medicines, and because of this process, more often than not it is the recommended route to prescribe licensed medicines. That being said, prescribing unlicensed compounded menopause medicines may be necessary, especially when it comes to the patient’s specific need and interests and where licensed medicines have been unable to satisfactorily meet the needs of the patient or are unsuitable for them.

Utilising compounded menopause medicine as a method to enhance patient care could be beneficial for the many patients that need specific dosing or formulation requirements, but sadly more often than not we see delays to patient needs and treatment, as the rise of mass manufactured licensed medicines have grown in popularity. Compounding menopause medicine could offer huge potential for many, but prescribing practices have moved towards evidence-based medicines because of the responsibility imposed on prescribers for prescribing compounded therapies. Clinicians need to understand that even licensed products are not safe or effective for all patients particularly if the product is being used in a population that were not part of the original clinical trials for the drug.

It is important to know that compounding pharmacies and pharmacists in the UK are also regulated and licensed by the General Pharmaceutical Council (GPhC). The GPhC set standards for pharmacists and pharmacies to meet to remain on their register with the aim to protect the public and give them assurance that they will receive safe and effective care when using pharmacy services.

So even though compounded medicines are ‘unlicensed’, there is a lot of due diligence exercised by the pharmacists to ensure the products meet the safe and effective care criteria. This is generally demonstrated through the purchase of medical grade active and inactive pharmaceutical ingredients (with certificates of analysis and safety data sheets), trained staff, following and updating SOPs, audits, traceability of ingredients and products during recalls, as well as continuous learning and error reporting being supported in the pharmacy.

Ultimately, how compounded menopause medicine is viewed will depend on the knowledge and experience of the patients and professionals involved. Although the medicine is unlicensed it is important to understand that experienced clinicians and pharmacists involved in the process of making the decisions are regulated, and patients are consistently monitored during their response to the medicine. If compounded menopause medicine was integrated in the healthcare system, it could change and improve the quality of life of many patients suffering with debilitating menopause symptoms, and we hope as a pharmacy that in the future we will see a shift in how compounded medicine is viewed.

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Lifestyle

We need more than investment in services to solve the mental health crisis.

By Lea Milligan

It’s now widely recognised that there is a crisis in mental health. In September, a staggering 1.6m people in the UK are waiting for mental health treatment on the NHS, and 1 in 4 people globally are impacted by a mental illness at some point in their life.

This crisis is only being exacerbated by the increasing cost of living, global conflicts causing generational trauma and the ongoing fallout from COVID-19.

Lack of equitable access to services, treatment and resources means the most vulnerable in society continue to suffer disproportionately.

Everyone assumes that addressing this crisis requires more doctors, more appointments and more mental health treatment centres. Whilst one answer is, yes, we absolutely need more of these, it’s not the only answer.

More services are not the sole solution: We also need more research.

Mental health research is the secret weapon that often is overlooked by policy makers.

  • Research shows us where to focus resources, so that we don’t just blindly throw money and time at the parts of the system that are not working.
  • Research helps move people through the system faster, giving them more effective treatments and faster diagnoses.
  • Research reduces the number of people requiring acute care by providing effective prevention strategies and intervention methods.

Research speeds up access to services:

The EnCAMHS project, sponsored by Greater Manchester Mental Health NHS Foundation Trust, is working to improve and refine the referral process to CAMHS (Child and Adolescent Mental Health Services). By mapping and raising awareness among professionals of the different types of support available for children and young people, the EnCAMHS team are hoping to reduce waiting lists and speed up access to care for the most urgent cases.

Research improves treatments:

I have seen firsthand the incredible breakthroughs in treatments that have come from targeted investment in research.

MQ researcher Dr Colette Hirsch from King’s College London developed a new treatment for anxiety and depression called cognitive bias modification for interpretation (CBT-I). New treatments such as this help provide a greater range of treatment choices, more important now than ever because, according to the World Health organisation, the pandemic triggered a 25% increase in anxiety and depression worldwide.

Dr Jennifer Wild from Oxford University has developed a new treatment for PTSD in health care workers, with a 90% recovery rate. This is an unprecedented success rate for a group highly vulnerable to traumatic stress.

And Dr Ethel Mpungu has developed a community-based therapy for people living with both depression and AIDS in rural Uganda. The 578 participants of her study remained symptom free from depression 12 months later. Her work has been internationally recognised and, due to its success and cost-effectiveness, it is being rolled out across other African nations, improving the lives of millions of people.

Research can help us prevent mental ill-health in the first place:

For example, the IDEA (Identifying Depression in Early Adolescence) project has created a prediction model to identify the young people who are most at risk of developing depression in later life. This tool can be used to identify the most vulnerable before depression can take hold, getting them timely interventions that can prevent a lifetime of mental ill-health.

This Mental Health Awareness Week (9-15 May), plenty of people will be talking about smashing stigmas, reducing loneliness and the need for more mental health support. And, of course, these are absolutely important. Vital even. But don’t forget about research.

Because it is only through research that we can truly make progress.

Lea Milligan is CEO of MQ Mental Health Research, a charity that funds world-class research and innovation to create better mental health care.

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