Few things bring more angst to parents than the pain and suffering of their child. When their child has a debilitating disease, the parents’ sense of powerlessness can be overwhelming. They want a miracle cure as soon as possible — and look to doctors to provide one.
Pressure from parents – including pro-active citizen lobbying — can be an important driver of medical research priorities. But medical entrepreneurs and their funders can also exploit public pressure to promote “breakthrough” research discoveries that are exaggerated and end up raising expectations unrealistically.
Juvenile diabetes – also known as Type 1 diabetes or T1D for short — may be one of the latest examples of this phenomenon. Since the 1990s, talk of a “cure” for a disease that afflicts some 1.5 million Americans — with 200,000 new cases annually – has been growing. T1D is less well known than its sibling, Type 2 diabetes (T2D), which affects nearly 100 million Americans – and is getting worse by the day
The two diseases share a common problem – excess glucose sugar, but there the similarities largely end. T2D is a largely a diet and lifestyle disease that is treatable and highly manageable if the sufferer takes corrective action. It generally shows up in adulthood after years of no exercise and poor eating habits, including a high-calorie diet filled with soda pop and junk food.
T1D, by contrast, is a genetic auto-immune disease. Children are born unable to preserve the insulin generated by their pancreas. Without insulin, their glucose ends up in their bloodstream, limiting their ability to turn food into fuel. The result is a variety of debilitating symptoms including fatigue, extreme thirst, unintended weight loss, frequent urination, and blurred vision. Over time, and without proper management, T1D can lead to heart disease, blood vessel deterioration and nerve, kidney and eye damage.
T1D can be managed, but it’s a tedious and often painful lifelong process. Most T1D sufferers receive hands-on family and medical support from an early age. The main treatment regimen is daily insulin injections, sometimes as many as three. Even in adulthood, those with T1D typically make regular visits to specialized health clinics with endocrinologists, ophthalmologists, and dieticians on staff to monitor their food intake and glucose levels.
Any intervention that can make this process easier and less fraught with peril is welcome, of course. Over the years, injection and glucose monitoring techniques have become more user-friendly. But is science any closer to eliminating the real source of the problem? That’s where agreement in the medical establishment seems to end.
In theory, there are two ways one might try to “cure” T1D. One is to create replacement “beta” cells for the insulin-generating cells destroyed by the sufferer’s immune system. One might inject those cells into the pancreas or try to introduce them elsewhere (on the assumption that they will be better protected). The second solution is to target the immune system, to suppress its ability to destroy insulin-generating cells in the first place. Of course, combining both of these techniques would be ideal.
However, science has tried – and repeatedly failed in each case – in one clinical trial after another. There’s been success in the laboratory, and with mice, but it hasn’t translated to human test subjects. Fresh efforts are being made using more advanced techniques, and once again, hopes of success are high. The question as in past years is whether scientists are once again leading the public – and T1D sufferers – on.
A good example of how the T1D “cure” controversy typically plays out is the debate over BCG. BCG is a vaccine that has long been used successfully against tuberculosis. In ongoing Phase III clinical trials, victims of multiple sclerosis are also showing marked improvement. Preliminary evidence suggests that the same degree of success may be possible with T1D. In Phase II trials, BCG is increasing the amount of insulin emanating from the pancreas by 40% — nothing to shake a stick at.
The current T1D testing with BCG is being led by Dr. Denise Faustman at Massachusetts General Hospital, who seems ready to predict victory. Faustman predicts full-scale FDA approval within the next three years. “Because of the size of our Phase II trial and BCG’s known safety profile and its generic drug status, we are hoping to pursue approval coming out of Phase II trial by 2022,” she says.
But leading funders in the diabetes field think that Faustman is over-selling BCG. In an unprecedented move, the American Diabetes Association and the Junior Diabetes Research Foundation, which refused to fund Faustman’s research, have issued an advisory suggesting that BCG’s promise as a diabetes cure is “inflated.”
Faustman was one of the diabetes researchers who touted her success with laboratory mice back in 2001. She’s spent nearly two decades trying to replicate that success with humans. Is it professional jealousy that is leading the “Big Dogs” in the diabetes field to doubt her research findings – or is there genuine concern that she’s engaged in shameless self-promotion without a real scientific leg to stand on?
Faustman herself says she is dumb-founded. “I am still not sure why they chose to issue [the advisory] but it was a political not a scientific response to our work,” she insists.
Faustman admits to at least one hitch. In MS sufferers, the BCG vaccine takes nearly four years to start working. Could the same delay – or even a longer one – occur with T1D? She doesn’t know. No one does until further testing is done.
For outsiders, it’s difficult to sort through these issues and arrive at a sober conclusion. There are other innovative diabetes research efforts underway, including the development of Encaptra implants, a technology that, in theory, allows T1D sufferers to receive a steady stream of insulin-generating cells under their skin without the need for daily injections. VitaCyte, the firm that has developed Encaptra, hopes to “vascularize” the production of these cells so that they enter the T1D sufferer’s bloodstream and become self-generating. Presently, the implant device needs to be replaced yearly.
Independent diabetes experts are cautious about these new initiatives, which also include some promising stem cell applications. Even if they pan out, it’s highly unlikely that a “cure” for T1D is right around the corner. It could take years of additional testing before a product is available commercially.
Kristina Figueroa, a leading T1D patient advocate in Philadelphia, was diagnosed with the disease at age 9. She still adheres to the tedious injection and glucose monitoring regimen that has saved her life for decades. She says she’s still patiently waiting for a long-promised medical breakthrough.
“We still have a long way to go,” she says.